scholarly journals Effects of Yixintai Pills on Myocardial Cell Apoptosis in Rats With Adriamycin-Induced Heart Failure

2020 ◽  
Vol 23 (2) ◽  
pp. E234-E238
Author(s):  
Liting Zhang ◽  
Dan Chen ◽  
Min Peng ◽  
Hongbo Ma
Keyword(s):  
Cell Apoptosis ◽  
Myocardial Cell ◽  
Left Ventricular ◽  
Control Group ◽  
Myocardial Cells ◽  
Model Group ◽  
Vacuolar Degeneration ◽  
Expression Levels ◽  
Tnf Α ◽  
Gsk 3Β

Objective: To study the effects of Yixintai pills on myocardial cell apoptosis in rats with adriamycin (ADR)-induced heart failure (HF) and the mechanism of action. Methods: Sixty healthy male Wistar rats randomly were divided into Control, Model, Captopril, and Yixintai pill groups. A rat model of ADR-induced HF was constructed by intraperitoneal injection of ADR (2.5 mg/kg). The control group was given an equal volume of normal saline; the Yixintai pill and Captopril groups were given corresponding mediations (5 mg/kg) by lavage. After 4 weeks of treatment, fasting blood was collected to detect the contents of plasma rennin activity (PRA), angiotensin II (AngII), and aldosterone (ALD). B ultrasound was used to detect the heart structure, and the heart weight/body weight (HW/BW) ratio was calculated. The pathology of myocardial tissues was observed by HE staining. The apoptosis of myocardial cells was detected by TUNEL assay. The expression levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in serum were analyzed by ELISA, and the protein expression levels of protein kinase B (Akt), phosphorylated (p)-Akt, glycogen synthase kinase-3β (GSK-3β) and p-GSK-3β in myocardial tissues were measured by Western blotting. Results: Compared with the Control group, the PRA, AngII, ALD, left ventricular posterior wall thickness at end-systole (LVPWs), left ventricular posterior wall thickness at end-diastole (LVPWd), interventricular septal thickness at end-systole (IVSs), interventricular septal thickness at end-diastole (IVSd), HW/BW, TNF-α and IL-6 of model group increased significantly (P < .05). PRA, AngII, ALD, LVPWs, LVPWd, IVSs, IVSd, HW/BW, TNF-α and IL-6 of the Yixintai pill and Captopril groups were significantly lower than those of the Model group (P < .05). There were no significant differences in the indices between the Yixintai pill and Captopril groups (P > .05). In the Model group, lamellar necrosis, vacuolar degeneration, increased myocardial fibers and lamellar dissolution of myocardial cells were found in myocardial tissues. However, the myocardial cells of the Control group were neatly arranged and clearly structured, and only a few ones underwent fibrosis. There were mild myocardial fibrosis and vacuolar degeneration in the Yixintai pill and Captopril groups, and the degeneration and hyperplasia of myocardial fibers were obviously relieved. Compared with the Control group, the apoptosis index (AI) of the Model group increased significantly (P < .05). The AI values of the Yixintai pill and Captopril groups were significantly lower than those of the Model group (P < .05). Compared with the Control group, the expression levels of p-Akt and p-GSK-3β in the Model group decreased significantly (P < .05). The expression levels of p-Akt and p-GSK-3β in the Yixintai pill and Captopril groups were significantly higher than those of the Model group (P < .05), whereas the former 2 groups had similar results (P > 0.05). Conclusion: Yixintai pills may inhibit myocardial cell apoptosis and ventricular remodeling in rats by up-regulating PI3K/Akt/GSK-3β signal, thus protecting the heart function.

scholarly journals Effect of Massage on the TLR4 Signalling Pathway in Rats with Neuropathic Pain

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Qian Wang ◽  
Jing Lin ◽  
Peng Yang ◽  
Yingye Liang ◽  
Dongming Lu ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Spinal Nerve ◽  
Signalling Pathway ◽  
Inflammatory Factors ◽  
Control Group ◽  
Group Model ◽  
Model Group ◽  
Expression Levels ◽  
Tnf Α ◽  
Massage Group

This study set out to investigate the effect of massage on the Toll-like receptor 4 (TLR4) signalling pathway in the dorsal root ganglia of rats that had undergone spinal nerve ligation (SNL), with the hypothesis that massage could be used as an analgesic. Forty female SD rats were randomly divided into 5 groups: the control group, sham-operated group, model group, sham massage group, and massage group. There were 8 rats in each group. SNL rat models were established in the model group, sham massage group, and massage group. Rats in the sham-operated group underwent surgery to expose the vertebral nerves, but no further procedures were performed. The control group consisted of intact animals. The rats in the massage group underwent massage using a massage simulation machine once a day for 14 d in succession; the hind limbs of the rats in the sham massage group were gently touched with a cloth bag once a day for 14 continuous days. The rats in the control group, the sham-operated group, and the model group did not receive any intervention and were observed for 14 d. Paw withdrawal thermal latency (PWTL) and paw withdrawal mechanical threshold (PWMT) of rats in each group were detected 1 d before modelling and at 1, 3, 7, and 14 d after modelling. Fourteen days after modelling, the expression levels of TLR4, IRAK1, TRAF6, TNF-α, and IL-6 were detected in all rats. The PWTL and PWMT of SNL rats were decreased, while these parameters were elevated after massage. SNL rats showed higher levels of TLR4, IRAK1, TRAF6, IL-6, and TNF-α, and massage effectively lowered the expression levels of these molecules. Inhibiting activation of the TLR4 signalling pathway, which can reduce the release of inflammatory factors, may be one mechanism by which massage treats neuropathic pain.

scholarly journals Pharmacodynamic Study of QingFei Paidu Decoction in the Treatment of Acute Respiratory Distress Syndrome Caused by Coronavirus Disease-2019 (COVID-19)

2021 ◽  
Author(s):  
Zhixian He ◽  
Xinyv Wang ◽  
Xing Wang ◽  
Jinyue Wang
Keyword(s):  
Male Rats ◽  
Arterial Oxygen ◽  
Good Effect ◽  
Control Group ◽  
Group Model ◽  
Protective Effects ◽  
Model Group ◽  
Blank Control Group ◽  
Expression Levels ◽  
Tnf Α

Abstract Background: The outbreak of the Coronavirus Disease-2019 (COVID-19) has threatened the public health of the world, and may eventually lead to acute respiratory impoverishment syndrome (ARDS). ARDS is a clinical syndrome caused by intrapulmonary or extrapulmonary reasons, which has complex pathogenesis and high mortality rate, it’s also one of the important factors in death from the 2019 novel coronavirus (2019-nCoV) epidemic. It has been reported that traditional Chinese medicine (TCM) can exert a good effect in the process of treatment. The present study aimed to observe the protective effects of TCM formula Qingfei Paidu Decoction (QFPD) on ARDS rats and explore the pharmacodynamic mechanism of the compound. Methods: 24 male rats were randomly divided into 4 groups (n=6), blank control group, model group, QFPD group (18.6g·kg-1·d-1) and dexamethasone group (2mg·kg-1·d-1). Blank control group rats were given saline, whereas other groups were injected with oleic acid (OA) and lipopolysaccharide (LPS) successively to establish ARDS model, and observed the behavioral performance of rats after model building. The morphological changes of lung tissue under optical microscope were observed; rat lung index (LI) and lung permeability index (LPI) were measured; blood PH, partial arterial oxygen pressure (PaO2, mmHg), partial arterial carbon dioxide pressure (PaCO2, mmHg), arterial oxygen saturation (SaO2) were measured by blood gas analyzer; the levels of tumor necrosis factor-α (TNF-α), interleukin (IL-1β, IL-6, IL-8, IL-10), thromboxane B2 (TXB2), 6-keto-prostaglandin F1α (6-keto-PGF1α), kerbs von lungren 6 antigen (KL-6), C-reactive protein (CRP), and the expression of superoxide dismutase (SOD) were measured via test kit.Results: Compared with the model group, the two treatment groups could improve the respiratory and lung injury in rats, and could restore the expression levels of thromboxane, various cytokines and protein to varying degrees.Conclusions: QFPD and dexamethasone have protective effects on ARDS rats induced by jointly injecting OA and LPS, and QFPD has the better effect in between. These may be related to reducing the expression levels of IL-1β, IL-6, IL-8, TNF-α, CRP, TXB2, KL-6, and increasing the contents of IL-10, 6Keto-PGF1a and SOD vitality in the body.

scholarly journals Effect of Musk Tongxin Dropping Pill on Myocardial Remodeling and Microcirculation Dysfunction in Diabetic Cardiomyopathy

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Jingjing Zhao ◽  
Yan Zhou ◽  
Huahua Liu ◽  
Zhaohai Zheng ◽  
Shuqing Liu ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Diabetic Cardiomyopathy ◽  
Left Ventricular ◽  
Control Group ◽  
Myocardial Remodeling ◽  
Myocardial Cells ◽  
Apparent Increase ◽  
Tnf Α ◽  
Heart Mass ◽  
Microcirculation Dysfunction

Objective. To explore the effect of Musk Tongxin Dropping Pill (MTDP) on myocardial remodeling and microcirculation dysfunction in diabetic cardiomyopathy (DCM). Methods. Forty male SD rats were randomly divided into control group (control group, n = 10), DCM model group (DCM group, n = 10), DCM model + pioglitazone group (DCM + PLZ group, n = 10), and DCM model + MTDP group (DCM + MTDP group, n = 10). An intraperitoneal single injection of 65 mg/kg streptozotocin (STZ) was used to establish rat model of DCM and the rats in control group were treated with the same dose of sodium citrate buffer solution. DCM + PLZ group was treated with 3 mg/kg/d PLZ by ig after modeling, DCM + MTDP group was treated with 22 mg/kg/d MTDP by ig, and DCM group was treated with 2 ml/kg/d sodium carboxymethyl cellulose (CMC-Na) by ig. The general condition of rats was continuously observed. After intervening for 3 weeks, the random blood glucose of rats was detected by tail vein, and the echocardiography examination was performed. Blood specimens were collected from the abdominal aorta, serum nitric oxide (NO) and endothelin-1 (ET-1) were detected to estimate endothelial function, and tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), IL-1β, malondialdehyde (MDA), and superoxide dismutase (SOD) were detected to observe the changes of inflammation and oxidative stress indexes. The heart mass index (HMI) was calculated through the ratio of heart mass (HM) to the corresponding body mass (BM). Myocardial pathological tissue staining was performed. Results. Compared with control group, blood glucose in other three groups was higher. Left ventricular end systolic diameter (LVSD) and left ventricular end diastolic diameter (LVDD) in DCM group showed a significant increase, while left ventricular ejection fraction (LVEF) and heart rate (HR) in this group displayed an obvious decrease P < 0.01 . BM and HM in DCM group exhibited a reduction, and HM/BM × 103 revealed an apparent increase P < 0.01 . The levels of serum NO and SOD were distinctly downregulated P < 0.01 , and the levels of ET-1, MDA, TNF-α, IL-1β, and IL-6 were remarkably upregulated P < 0.01 . Compared with DCM group, a significant decrease was observed in LVSD and LVDD in DCM + MTDP group, while LVEF and HR obviously increased P < 0.05 . BM and HM indicated an apparent increase, but HM/BM ×103 reduced distinctly P < 0.01 . The levels of serum NO and SOD were markedly upregulated P < 0.05 , and the levels of ET-1, MDA, TNF-α, IL-1β, and IL-6 were significantly downregulated P < 0.05 . HE staining showed that myocardial cells arranged neatly in the control group but not in the DCM group. The intercellular space between myocardial cells in DCM group increased, accompanied by damage of myocardial fibers and infiltration of inflammatory cells. Masson staining displayed an increase in interstitial collagen fibers in DCM group. Carstairs staining showed that microembolization occurred in the myocardium in DCM group, while in DCM + MTDP and DCM + PLZ groups the corresponding myocardial pathological changes were significantly improved. Conclusions. MTDP might show a positive effect on myocardial remodeling and microcirculation dysfunction in DCM rats.

scholarly journals Hepatoprotective effect of galangin on carbon tetrachloride-induced hepatotoxicity via the LKB1/AMPK pathway

2021 ◽  
Vol 19 ◽  
pp. 205873922110008
Author(s):  
Meng Chen ◽  
Xinyan Song ◽  
Jifang Jiang ◽  
Lei Xing ◽  
Pengfei Wang
Keyword(s):  
Carbon Tetrachloride ◽  
Liver Toxicity ◽  
Corn Oil ◽  
Histopathological Examination ◽  
Hepatoprotective Effect ◽  
Control Group ◽  
Group Model ◽  
Protective Effects ◽  
Model Group ◽  
Expression Levels

To investigate the protective effects of galangin on liver toxicity induced by carbon tetrachloride (CCl4) in mice. Mouse hepatotoxicity model was established by intraperitoneal injection (i.p.) of 10 ml/kg body weight CCl4 that diluted with corn oil to a proportion of 1:500 on Kunming mice. The mice were randomly divided into five groups named control group, model group, and 1, 5, and 10 mg/kg galangin group. The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed by ELISA. Liver histopathological examination was observed via optical microscopy. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), and glutathion (GSSG) were analyzed to assess oxidative stress. Finally, western blot assay was carried out to analyse the expression levels of total AMP-activated protein kinase (AMPK), phospho-AMPK (p-AMPK), total liver kinase B1 (LKB1), and phospho-LKB1 (p-LKB1). Compared with the control group, in the model group, the levels of AST, ALT, MDA, and GSSG increased significantly ( p < 0.01); the activity of SOD and GSH decreased significantly ( p < 0.01); and the histopathological examination revealed liver necrosis. However, treatment with galangin (5 and 10 mg/kg) significantly reversed these CCl4-induced liver damage indicators. Furthermore, treatment with galangin (10 mg/kg) significantly increased the p-AMPK and p-LKB1 expression levels ( p < 0.01). This study supports the hepatoprotective effect of galangin against hepatotoxicity, perhaps occurring mainly through the LKB1/AMPK-mediated pathway.

scholarly journals Selective TNF-α targeting with infliximab attenuates impaired oxygen metabolism and contractile function induced by an acute exposure to air particulate matter

2015 ◽  
Vol 309 (10) ◽  
pp. H1621-H1628 ◽  
Author(s):  
Timoteo Marchini ◽  
Verónica D'Annunzio ◽  
Mariela L. Paz ◽  
Lourdes Cáceres ◽  
Mariana Garcés ◽  
...  
Keyword(s):  
Particulate Matter ◽  
Saline Solution ◽  
Contractile Function ◽  
Left Ventricular ◽  
Acute Exposure ◽  
Control Group ◽  
Contractile Reserve ◽  
Mice Model ◽  
Cardiovascular Morbidity And Mortality ◽  
Tnf Α

Inflammation plays a central role in the onset and progression of cardiovascular diseases associated with the exposure to air pollution particulate matter (PM). The aim of this work was to analyze the cardioprotective effect of selective TNF-α targeting with a blocking anti-TNF-α antibody (infliximab) in an in vivo mice model of acute exposure to residual oil fly ash (ROFA). Female Swiss mice received an intraperitoneal injection of infliximab (10 mg/kg body wt) or saline solution, and were intranasally instilled with a ROFA suspension (1 mg/kg body wt). Control animals were instilled with saline solution and handled in parallel. After 3 h, heart O2 consumption was assessed by high-resolution respirometry in left ventricle tissue cubes and isolated mitochondria, and ventricular contractile reserve and lusitropic reserve were evaluated according to the Langendorff technique. ROFA instillation induced a significant decrease in tissue O2 consumption and active mitochondrial respiration by 32 and 31%, respectively, compared with the control group. While ventricular contractile state and isovolumic relaxation were not altered in ROFA-exposed mice, impaired contractile reserve and lusitropic reserve were observed in this group. Infliximab pretreatment significantly attenuated the decrease in heart O2 consumption and prevented the decrease in ventricular contractile and lusitropic reserve in ROFA-exposed mice. Moreover, infliximab-pretreated ROFA-exposed mice showed conserved left ventricular developed pressure and cardiac O2 consumption in response to a β-adrenergic stimulus with isoproterenol. These results provides direct evidence linking systemic inflammation and altered cardiac function following an acute exposure to PM and contribute to the understanding of PM-associated cardiovascular morbidity and mortality.

Effect of Curculigo orchioides on Reflux Esophagitis by Suppressing Proinflammatory Cytokines

2012 ◽  
Vol 40 (06) ◽  
pp. 1241-1255 ◽  
Author(s):  
Sae-Kang Ku ◽  
Jae-Soo Kim ◽  
Young-Bae Seo ◽  
Yong-Ung Kim ◽  
Seung-Lark Hwang ◽  
...  
Keyword(s):  
Reflux Esophagitis ◽  
Group Treatment ◽  
Control Group ◽  
Esophageal Mucosa ◽  
Dependent Manner ◽  
Protective Effects ◽  
Model Group ◽  
Curculigo Orchioides ◽  
Intact Group ◽  
Tnf Α

This study was performed to investigate effects of Curculigo orchioides rhizome (curculiginis rhizome) on acute reflux esophigitis (RE) in rats that are induced by pylorus and forestomach ligation operation. Proinflammatory cytokine, as well as tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 were all assayed and the expression of TNF-α and COX2 analyzed by RT-PCR. The esophagic tissue damage of reflux esophagitis rat was increased compared to that of normal intact group. However, the esophagic damage percentage from the extract of curculiginis rhizoma (ECR) 600 mg/kg and ECR 300 mg/kg were significantly lower than that of the RE control group. Administration of α-tocopherol (30 mg/kg) and ECR (600 mg/kg, 300 mg/kg, and 150 mg/kg) had a significant effect on the gastric acid pH in rats with induced reflux esophagitis (p < 0.05). The treatment with ECR significantly reduced the production of cytokines TNF-α, IL-1β and IL-6 levels compared to the model group (p < 0.05). The expression of TNF-α and COX2 in the intact esophageal mucosa was low while those of the RE control group were significantly higher due to an inflammatory reaction in the esophagus. Compare to the model group, treatment with α-tocopherol or ECR significantly inhibited the expression levels of COX2 and TNF-α in a dose-dependent manner. These results suggest that anti-inflammatory and protective effects of ECR could attenuate the severity of reflux esophagitis and prevent esophageal mucosal damage.

Electrophysiologic properties and ventricular fibrillation in normal and myopathic hearts

1999 ◽  
Vol 77 (7) ◽  
pp. 510-519 ◽  
Author(s):  
Katherine M Kavanagh ◽  
Patricia A Guerrero ◽  
Bodh I Jugdutt ◽  
Francis X Witkowski ◽  
Jeffrey E Saffitz
Keyword(s):  
Ventricular Fibrillation ◽  
Myocardial Dysfunction ◽  
Myocardial Cell ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Control Group ◽  
Functional Abnormality ◽  
Ventricular Ejection Fraction ◽  
Anisotropic Properties

This study tests the hypothesis that moderate myocardial dysfunction is associated with altered myocardial anisotropic properties and structurally altered ventricular fibrillation (VF). Mongrel dogs were randomized to either a control group or a group that was rapidly paced at 250 beats/min until the left ventricular ejection fraction was [Formula: see text] 40%. Changes in anisotropic properties and the electrical characteristics of VF associated with the development of moderate myocardial dysfunction were assessed by microminiature epicardial mapping studies. In vivo conduction, refractory periods, and repolarization times were prolonged in both longitudinal and transverse directions in myopathic animals versus controls. VF was different in myopathic versus control animals. There were significantly more conducted deflections during VF in normal hearts compared with myopathic hearts. Propagated deflection-to-deflection intervals during VF were significantly longer in myopathic hearts compared with controls (125.5 ± 49.06 versus 103.4 ± 32.9 ms, p = 0.009). There were no abnormalities in cell size, cell shape, or the number of intercellular gap junctions and there was no detectable change in the expression of the gap junction proteins Cx43 and Cx45. Moderate myocardial dysfunction is associated with significant electrophysiological abnormalities in the absence of changes in myocardial cell morphology or intercellular connections, suggesting a functional abnormality in cell-to-cell communication.Key words: cardiomyopathy, anisotropy, fibrillation, defibrillation.

Lipidomics Study of the Therapeutic Mechanism of Plantaginis Semen in Potassium Oxonate-Induced Hyperuricemia Rat

2020 ◽  
Author(s):  
Wenjun Shi ◽  
Fei Yang ◽  
Liting Wang ◽  
Nankun Qin ◽  
Chengxiang Wang ◽  
...  
Keyword(s):  
Male Rats ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
High Dose ◽  
Intragastric Administration ◽  
Group Model ◽  
Model Group ◽  
Tnf Α ◽  
Plantaginis Semen ◽  
Potassium Oxonate

Abstract BackgroundPlantaginis semen has been widely used as folk medicine and health care food against hyperuricemia (HUA) and gout, but little was known about its pharmacological mechanism. MethodsThe model was established by potassium oxonate intragastric administration. 42 Sprague-Dawley (SD) male rats were randomly divided into the control group, model group, benzbromarone group (10 mg/kg) and three Plantaginis semen groups (n = 7). The Plantaginis semen groups were treated orally with Plantaginis semen at 0.9375, 1.875 and 3.75 g/kg for 28 days. The levels of serum uric acid (UA), creatinine (Cr), triacylglycerol (TG) and tumor necrosis factor-α (TNF-α) were detected using enzyme-linked immunosorbent assay kits. Ultra performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-Q-TOF/MS) was used as the basis for serum lipidomics analysis, and orthogonal partial least squares discriminant analysis (OPLS-DA) was carried out for the pattern recognition and characteristic metabolites identification. The relative levels of critical regulatory factors of urate anion transporter 1(URAT1) and phosphatidylinositol 3-kinase/ protein kinases B (PI3K/Akt) were determined by quantitative real-time polymerase chain reaction (RT-qPCR). ResultsCompared with the model group, the levels of serum UA, Cr, and TG were significantly (p<0.01) decreased in benzbromarone and three Plantaginis semen groups and the level of serum TNF-α was significantly (p<0.05) decreased in benzbromarone and low dose of Plantaginis semen group. With lipidomics analysis, significant lipid metabolic perturbations were observed in HUA rats, 13 metabolites were identified as potential biomarkers and glycerophospholipid metabolism pathway was mostly affected. These perturbations can be partially restored via treatment of benzbromarone and Plantaginis semen. Additionally, the URAT1 and PI3K/Akt mRNA expression levels were significantly decreased (p<0.05) after treatment with benzbromarone and high dose of Plantaginis semen. ConclusionsPlantaginis semen had significant anti-HUA, anti-inflammatory and renal protection effects and could attenuate potassium oxonate-induced HUA through regulation of lipid metabolism disorder. Trial registrationNot applicable

scholarly journals Effect of Shenfu Qiangxin on the expression of TGF-β/Smads signaling pathway-related molecules in myocardium of rats with heart failure

2019 ◽  
Vol 17 ◽  
pp. 205873921985285
Author(s):  
Li Xiong ◽  
Guobo Xie ◽  
Binhua Luo ◽  
Zhiliang Mei
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Signaling Pathway ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Tgf Beta ◽  
Model Group ◽  
Ventricular Ejection Fraction ◽  
Tnf Α ◽  
Losartan Group

This study aims to evaluate the effect of Shenfu Qiangxin on TGF-β/Smads signaling pathway-related molecules in myocardial tissue of rats with heart failure. Five rats were selected as sham-operated group, while another 15 rats with heart failure were divided into three groups, including model group, losartan group, and Shenfu Qiangxin group. Rats in losartan group were given losartan intragastric intervention, the rats in Shenfu Qiangxin group were given Shenfu Qiangxin mixture intervention, while rats in another two groups were given equal volume of sterile saline intervention. During the treatment, the levels of B-type brain natriuretic peptide (BNP), lactate dehydrogenase (LDH), free fatty acids (FFA), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and TGF-β/Smads signaling pathway were measured in rats. Compared with model group, the expression of ejection fraction (EF), left ventricular ejection fraction (LVSP), TGF-β 1, Smad2, and Smad3 significantly decreased in sham-operated group, losartan group, and Shenfu Qiangxin group, while left ventricular end-diastolic volume (LVEDV), left ventricular end-diastolic diameter (LVDd), left ventricular end-diastolic pressure (LVEDP), BNP, LDH, FFA, TNF-α, and IL-6 levels increased ( P < 0.05). Compared with sham-operated group, the expression of EF, LVSP, TGF-beta 1, Smad2, and Smad3 dramatically decreased in losartan group, Shenfu Qiangxin group, but LVEDV, LVDd, LVEDP, BNP, LDH, FFA, TNF-α, and IL-6 levels increased ( P < 0.05). Compared with losartan group, the expression of EF, LVSP, TGF-beta 1, Smad2, and Smad3 upregulated in Shenfu Qiangxin group, while LVEDV, LVDd, LVEDP, BNP, LDH, FFA, TNF-α, and IL-6 levels downregulated ( P < 0.05). Consequently, Shenfu Qiangxin could effectively improve the heart function of rats with heart failure, and play an anti-heart failure role by regulating the expression of related molecules of TGF-β/Smads signaling pathway.

Increased Expression of TLR2 and TLR4 in Mononuclear Cells in Patient with Immune Thrombocytopenic Purpura.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3847-3847 ◽  
Author(s):  
Yunfeng Cheng ◽  
Shanhua Zou ◽  
Feng Li
Keyword(s):  
Plasma Concentration ◽  
Mrna Expression ◽  
Mononuclear Cells ◽  
Control Group ◽  
Gene Expressions ◽  
Expression Levels ◽  
Tnf Α ◽  
Healthy Control ◽  
Ifn Γ ◽  
Mrna Expression Levels

Abstract Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by platelet destruction resulting from autoantibodies against self-antigens and T-cell mediated cytotoxicity. Toll-like receptors (TLRs) are pattern recognition receptors important in mediating the immune response and their activation can lead to production of cytokines. Recent data suggest that TLR2 and TLR4 are crucial for the production of inflammatory cytokines and play central role in autoimmune diseases, yet little is known about their roles in ITP. Here we examined the gene expressions of TLR2 and TLR4 in ITP patients. We hypothesize that significant differences will exist between pre-treatment and post-treatment in ITP patients with similar changes reflected in the plasma concentration of cytokines. Total RNA was extracted from mononuclear cells obtained from 12 ITP patients and 15 healthy subjects. TLR2 and TLR4 mRNA expression levels were analyzed using a quantitative real-time PCR method and their protein expressions were validated by western blot. Plasma concentrations of cytokines IL-2, IFN-γ and TNF-α were measured by ELISA. Correlation analyses were carried out between the mRNA expression levels of TLR2 or TLR4 and the plasma levels of IL-2, IFN-γ and TNF-α. The gene expression of TLR2 and TLR4 were significantly increased in ITP patients comparing to healthy control group (p < 0.05 and p < 0.01, respectively). In addition their mRNA expression levels were decreased back into normal range after remission in 8 patients (p > 0.05, compared to healthy control group). Significantly positive correlations were found between the TLR2 mRNA expression level and the plasma concentration of IFN-γ or TNF-α (R = 0.75, p < 0.05; R = 0.83, p < 0.05, respectively). Changes in the gene expression of TLR4 and in the plasma concentration of IFN-γ or TNF-α were also significantly correlated (R = 0.82, p < 0.05; R = 0.88, p < 0.05, respectively). Directional changes in TLR2 / TLR4 and IFN-γ /TNF-α expression were concordant. However, there was no correlation found between TLR2 / TLR4 and IL-2. Differences in TLR2 and TLR4 expression strongly correlated with changes in IFN-γ and TNF-α suggest that the increased gene expressions of TLR2 and TLR4 in ITP patients may contribute to the pathophysiological progression of this disease by increasing the secretion of IFN-γ and TNF-α. Additional studies need to be performed to further clarify the role of TLRs -cytokines pathway in ITP.

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