Down-Regulation of Mir-21 Alleviates Lung Injury Induced by Burns Through Activating Silent Mating Type Information Regulation 2 Homolog 1 (SIRT1)-Protein Kinase B (AKT)-Nuclear Factor κB (NF- κB) Pathway

2020 ◽  
Vol 10 (4) ◽  
pp. 576-581
Author(s):  
Zhiyu Xu ◽  
Xiaohong Xie ◽  
Jia Tian ◽  
Huajie Wang ◽  
Zhenlin Lei ◽  
...  
Keyword(s):  
Lung Injury ◽  
Control Group ◽  
Group Model ◽  
Blood Gas ◽  
Model Group ◽  
Down Regulation ◽  
Sod Activity ◽  
Sirt1 Expression ◽  
Tnf Α ◽  
Sirt1 Inhibitor

Severe burns can cause lung damage. Mir-21 is a promising biomarker for inflammatory response. However, the expression and role of Mir-21 in lung injury have not been elucidated. SD rats were divided into control group; model group; Mir-21 inhibition group; Mir-21 inhibition + SIRT1 inhibitor (nicotinamide) group followed by analysis of Mir-21 expression by real time PCR, arterial blood gas index and lung wet-to-dry weight ratio, lung tissue MPO and SOD activities, protein content and cell count in bronchoalveolar lavage fluid, secretion of TNF-α and IL-2 by ELISA, SIRT1 expression by Real time PCR and ELISA and Akt and NF-κB level by Western blot. Compared with control group, model group showed significantly decreased PaO2 and pH, increased W/D and MPO activity increased, decreased SOD activity, increased protein content and cell count in BALF, Mir-21 expression, and secretion of TNF-α and IL-2, decreased SIRT1 expression, and promoted pAkt and NF-κB expression (P < 0 05). Down-regulation of Mir-21 significantly improved blood gas index, decreased W/D and MPO activity, increased SOD activity, decreased TNF-α and IL-2 secretion; increased SIRT1 expression, and decreased pAkt and NF-κB expression (P < 0 05). However, SIRT1 inhibitor significantly reversed the effect of down-regulation of Mir-21 on the protection of lung injury. Downregulation of Mir-21 regulates SIRT1-Akt-NFκB pathway and oxidative stress, reduces inflammation, and thus alleviates burn-induced lung injury, and may be a new option for treating acute lung injury.

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

Triptolide Improves Renal Injury in Diabetic Nephropathy Rats through TGF-β1/Smads Signal Pathway

2020 ◽  
Vol 20 ◽  
Author(s):  
Ruoyu Pang ◽  
Donghai Gu
Keyword(s):  
Diabetic Nephropathy ◽  
Renal Injury ◽  
Diabetic Rats ◽  
Control Group ◽  
Inflammatory Factor ◽  
Group Model ◽  
Model Group ◽  
Tnf Α ◽  
Smad7 Expression ◽  
Tgf Β1

Objective: To investigate the therapeutic effect and mechanism of Triptolide on renal injury in diabetic nephropathy rats. Methods: A total of 15 male SD rats aged 8 weeks were randomly divided into five groups (3 rats in each group): control group, model group, Triptolide low-dose (Triptolide-L) group, Triptolide medium-dose (Triptolide-M) group, Triptolide high-dose (Triptolide-H) group. The rats models of diabetic nephropathy (DN) were established by a single intraperitoneal injection of STZ after being fed with high-fat and high-sugar diet for 4 weeks, and the fasting blood glucose (FBG) concentration of rats was detected. After 4 weeks, HE-staining was used to evaluate the renal pathological damage in rats; biochemical analysis was used to determine the blood urea nitrogen (BUN), serum creatinine (SCr), total cholesterol (TC), triglyceride (TG); ELISA was used to measure the serum inflammatory factor levels; Western blot (WB) was used to detect the expression of TGF-β1/Smads pathway proteins. Results: In the four FBG tests (once a week), the FBG concentration in the model group was significantly higher than that in the control group, while Triptolide-treated rats were significantly lower than that in the model group. Rats in Model group showed obvious renal injury, and Triptolide significantly improved the renal injury in DN rats. Compared with the control group, the expression of BUN, SCr, TC, TG, inflammatory factors TNF-α, IL-6 and IL-1β in the model group increased significantly. WB results showed that the expressions of TGF-β1, Smad3, α-SMA and vimentin in the kidney significantly increased, while the Smad7 expression significantly decreased. Triptolide significantly reduced the levels of BUN, SCr, TC, TG and TNF-α, IL-6, IL-1β in diabetic rats, decreased the expression of TGF-β1, Smad3, α-SMA, vimentin, and increased the Smad7 expression. In different doses of Triptolide treatment group, its effect showed a significant concentration dependence. Conclusion: Triptolide alleviates renal injury in diabetic rats by inhibiting the TGF-β1/Smads signaling pathway.

scholarly journals Protective effects of pterostilbene on ulcerative colitis in rats via suppressing NF-κB pathway and activating PPAR-γ

2019 ◽  
Vol 17 ◽  
pp. 205873921984015
Author(s):  
Liu Shi ◽  
Qing Liu ◽  
Jian-hua Tang ◽  
Jian-jun Wen ◽  
Chen Li
Keyword(s):  
Ulcerative Colitis ◽  
Activity Index ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Group Model ◽  
Protective Effects ◽  
Model Group ◽  
Trinitrobenzenesulfonic Acid ◽  
Ppar Γ ◽  
Tnf Α

Our study aimed to investigate the protective effects and potential mechanisms of pterostilbene on rats with ulcerative colitis (UC). We established 2,4,6-trinitrobenzenesulfonic acid (TNBS) induced colitis rat model. Rats were randomly divided into three groups, including control group, model group, and pterostilbene group (30 mg/kg). Disease activity index (DAI) including body weight, stool consistency, and gross bleeding was measured. The concentration of superoxide dismutases (SODs), glutathione superoxide (GSH-px), malondialdehyde (MDA), and methylpropanediol (MPO) in serum were detected by enzyme-linked immunosorbent assay (ELISA). The levels of interleukin-1 beta (IL-1β), IL-17, IL-6, and tumor necrosis factor–alpha (TNF-α) in serum were also analyzed by ELISA kits. Histological evaluations of colons were conducted. The levels of peroxisome-proliferator-activated receptor–γ (PPAR-γ), nuclear factor-κB (NF-κB), ZO-1, and Occludin were analyzed by immunohistochemistry. Compared with model group, pterostilbene notably suppressed the production of TNF-α, IL-17, IL-1β, IL-6, MDA and MPO in serum, and markedly increased the SOD and GSH-Px activity in serum. Pterostilbene significantly attenuated macroscopic damage and histological injury, when compared with model rats. Furthermore, pterostilbene also markedly activated the expression of PPAR-γ, ZO-1, and Occludin, and suppressed the expression of NF-κB. The protective effects of pterostilbene might be associated with suppression of NF-κB and activation of PPAR-γ. Pterostilbene might be a promising therapeutic agent for colitis treatment.

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 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.

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.

Experimental Study Oviductus ranae for the Change of α-SMA and TGF-β in Hepatic Fibrosis Rat Liver

2014 ◽  
Vol 912-914 ◽  
pp. 1940-1943
Author(s):  
Yan Li ◽  
Xiao Ou Li ◽  
Feng Hao ◽  
Lei Zhang ◽  
Lei Liu ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Hepatic Fibrosis ◽  
Rat Liver ◽  
Liver Tissue ◽  
Female Rats ◽  
Control Group ◽  
Group Model ◽  
Model Group ◽  
Model Control ◽  
Oviductus Ranae

To evaluate the control effect of Oviductus ranae on liver fibrosis in rats, and the change of TGF-β and α-SMA in liver of. To explore the mechanism of Oviductus ranae decoction on liver fibrosis. Methods Wistar female rats were randomly divided into a blank control group, model control group, colchicines group, Oviductus ranae group. Using the CCl4composite approach to make the rat modle. The course of treat-mart was 12 weeks.After treatment,All the rats was killed,and the materials and blood was taken,and to detect biochemical test of liver function after eight weeks. Investigating the variation of liver histology. Meanwhile detecting protein expression of TGF-β and α-SMA and by immunehistochemical method.Result The general condition of rats in all treatment groups are worse than the blank group,but better than the model group. And the rats in the model group were all occurred in liver fibrosis,and liver fibrosis is the most serious.In a normal rat liver tissue of TGF-β and α-SMA were significantly lower in model group and each treatment group, and there were significant differences, and the TGF-β and α-SMA in expression of liver tissue in model rats of TGF-β and α-SMA the highest. Conclusion: Oviductus ranae can effectively improve liver fibrosis rats induced by CC14liver function.Oviductus ranae can reduce the expression of TGF-β1in liver tissue of hepatic fibrosis rats induced by CCl4in. This may be one of the mechanisms of Oviductus ranae in prevention and treatment of liver fibrosis. Even though both increased expression of TGF-β and α-SMA expression, is able to determine TGF-β and α-SMA for the intervention of liver TGF-β signal transduction pathway in liver fibrosis.

scholarly journals Acute lung injury inhibition by juglone in LPS induced sepsis mouse model involves Sirt1 activation

2020 ◽  
Vol 19 (5) ◽  
pp. 1001-1007
Author(s):  
Qiong Hu ◽  
Chunai Yang ◽  
Fenshuang Zheng ◽  
Hongdan Duan ◽  
Yangshan Fu ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Mouse Model ◽  
Inflammatory Cytokines ◽  
Alveolar Epithelial Cells ◽  
Control Group ◽  
Western Blot Assay ◽  
Edema Formation ◽  
Sirt1 Expression ◽  
Treatment Groups

Purpose: To investigate the effect of juglone on LPS induced lung injury in a mouse model and in TC 1cell line.Methods: Edema formation in lungs were measured by determination of lung wet/dry weight. Expressions of various proteins were assessed by western blot assay, while Sirt1 level was assessed using immunohistochemistry. Mice were randomly assigned to nine groups of 10 mice each: normal control, untreated and seven juglone treatment groups. Acute lung injury was induced in mice by injecting LPS (10 mg/kg) via intraperitoneal route (ip). The treatment groups were given 10, 20, 30, 40, 50, 60 and 100 μM of juglone, ip, respectively.Results: The levels of MMP-9, IL-6, IL-1β and iNOS were significantly higher in acute lung injury induced mice compared than the control group (p < 0.05). Treatment of the mice with juglone significantly decreased LPS-induced up-regulation of inflammatory cytokines in a dose-dependentmanner. The production of inflammatory cytokines was almost completely inhibited in the mice treated with 100 mg/kg dose of juglone, while treatment of the LPS-stimulated TC 1 cells with juglone upregulated the expression of Sirt1 mRNA. Down-regulation of Sirt1 expression by siRNA inhibited the effect of juglone on LPS-induced increase in inflammatory cytokine production.Conclusion: Juglone prevents lung injury in mice via up-regulation of Sirt1 expression. Therefore, juglone might be useful for the development of a treatment strategy for lung injury. Keywords: Inflammatory, Sirtuin, Edema, Cytokines, Lung injury, TC 1 lung alveolar epithelial cells, Sirt1

scholarly journals Effect of Malus halliana Koehne Polysaccharides on Functional Constipation

2018 ◽  
Vol 16 (1) ◽  
pp. 956-962 ◽  
Author(s):  
Yingying Niu ◽  
Junya Wang ◽  
Pengyu Wang ◽  
Xiuchun Guo ◽  
Jinmei Wang ◽  
...  
Keyword(s):  
Substance P ◽  
Moisture Content ◽  
Dose Group ◽  
Low Dose ◽  
Functional Constipation ◽  
Positive Control ◽  
Positive Control Group ◽  
Control Group ◽  
Group Model ◽  
Model Group

AbstractThe effects of Malus halliana Koehne polysaccharides on functional constipation was investigated in this study. The rats were divided into six groups: normal group, model group, positive control group, M. halliana polysaccharides high dose groups 1200 mg/ kg, medium dose groups 1000 mg/ kg and low dose groups 800 mg/kg. The model of constipation was established by loperamide hydrochloride. Feces weight at 6 and 24 hours after treatment, Colon moisture content, in addition the levels of motilin (MTL), gastrin (Gas), somatostatin (SS), substance P (SP) in serum were used to evaluate the preventive effects of M. halliana polysaccharides on constipation. Compared with the model group, the positive control group, M. halliana polysaccharide high, medium and low dose group 6 h weight of feces, colon moisture content, the levels of motilin (MTL), gastrin (GAS) and substance P(SP) significantly (p <0.01) increased, the levels of somatostatin (SS) significantly decreased. The results indicated that the high, middle and low dosage of M. halliana polysaccharide could effectively improve functional constipation. Amongst these doses, the low dose group was better than others.

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