Study on the Regulation of Compound siRNA Nanoparticles on the Rat Model of Kidney Injury Induced by Sepsis by Inhibiting the Expression of NF-κB and P65

2021 ◽  
Vol 21 (2) ◽  
pp. 1345-1350
Author(s):  
Ye Chen ◽  
Xiaoxia Liu ◽  
Meiling Chen ◽  
Run Yan ◽  
Wenyu Song
Keyword(s):  
Rat Model ◽  
Group Treatment ◽  
Medical Image Analysis ◽  
Intervention Group ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Control Group ◽  
Image Analysis System ◽  
Model Group ◽  
Analysis System

This article explores the pathogenesis of sepsis AKI, and seeks to protect the acute damage of sepsis tissues and organs. This study is to prepare a rat sepsis-induced AKI model by CLP, and to observe the pathological changes of kidney tissue and the function of kidney changes, and observe the effect of siRNA nanoparticles on its intervention, preliminary explore the protective effect and possible mechanism of siRNA nanoparticles on AKI in sepsis rats, and provide more information for the clinical treatment of siRNA nanoparticles in sepsis theoretical and experimental basis. We analysis the benefit and deficiency of nuclear factor-κB (NF-κB) activation in the pathogenesis of glomerulonephritis and its regulatory effect on NF-κB activation. In the rat model group, no treatment was given after injection of nephrotoxic serum, and the rats were sacrificed on the 14th day; the compound siRNA nanoparticle intervention group (treatment group) was given dexamethasone 0.125 daily on the 1st to 14th day after nephrotoxic serum injection. Immunohistochemistry and medical image analysis system were used to observe NF-κB activation of monocyte chemotactic protein-1 (MCP-1) in glomeruli and tubules, and analyze their relationship with proteinuria and glomerular cells. The results showed that the expression of NF-κB in the glomeruli and tubules of the model group was significantly up-regulated regarding to the control group, and MCP-1’s expression in the glomeruli and tubules of the model group was higher than that of the control group. The activation of NF-κB and the expression of MCP-1 in glomeruli are closely related to monocyte infiltration and proteinuria; NF-κB activation and MCP-1 expression in glomeruli and tubules of the compound siRNA nanoparticles intervention group were significantly down-regulated. It was concluded that the activation of NF-κB has great impact on the pathogenesis of glomerulonephritis, and inhibition of NF-κB activation may be one of the mechanisms of anti-nephritis effect.

scholarly journals Tongfu Huoxue Decoction Reduces Autophagy and Apoptosis to Protect Against Acute Renal Injury in a Rat Model of Sepsis

2020 ◽  
Author(s):  
Yan Wang ◽  
Zixuan Wang ◽  
Qianlan Yang ◽  
Yuxin Fan ◽  
Lu Wang ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Rat Model ◽  
Renal Injury ◽  
Dose Group ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Control Group ◽  
Acute Renal Injury ◽  
Related Proteins ◽  
Dose Dependent

Abstract Background: To investigate the mechanism by which Tongfu Huoxue decoction protects against acute kidney injury in sepsis in rats, and provide a new therapeutic strategy for clinical intervention.Methods: Thirty-two Sprague–Dawley rats were randomly divided into a control group (saline), model group (lipopolysaccharide LPS group), LPS group+Tongfu Huoxue Decoction high-dose group (H group), and LPS group +Tongfu Huoxue Decoction low-dose group (L group). A rat model of acute kidney injury in sepsis was established by administration of LPS, and Tongfu Huoxue decoction was administered by gavage. The pathological and morphological changes of the kidneys were evaluated according to the levels of urea nitrogen (BUN) and blood creatinine (SCr). The expression of the inflammation-related factors IL-1b, IL-6 and TNF-a was determined by quantitative real-time PCR. Changes in the phosphorylation levels of the autophagy and apoptosis-related proteins LC3, beclin-1, caspase-3 and Akt were detected by Western blot analysis. Results: Compared with the model LPS group, kidney tissue damage was reduced in rats treated with Tongfu Huoxue decoction. The expression levels of inflammation-related and autophagy-related proteins in the kidney tissue of rats treated with Tongfu Huoxue decoction were significantly lower than those in the LPS group, which was showed a dose-dependent decrease in expression. After stimulation of HK-2 cells with LPS, the expression levels of the autophagy and apoptosis in the groups treated with Tongfu Huoxue decoction decreased in a dose-dependent manner. Furthermore, the rate of HK-2 cell apoptosis was higher in the LPS group than that in the control group, with lower rates in the H and L groups than that in the LPS group and were dose-dependent.Conclusion: Tongfu Huoxue decoction protects against acute renal injury in sepsis by reducing autophagy and apoptosis.

scholarly journals Effect of tripterine on Notch signaling pathway in IgA nephropathy rats

2018 ◽  
Vol 2 (6) ◽  
Author(s):  
Dan Liu
Keyword(s):  
Notch Signaling ◽  
Iga Nephropathy ◽  
Signaling Pathway ◽  
Intervention Group ◽  
Kidney Tissue ◽  
Renal Tissue ◽  
Notch Signaling Pathway ◽  
Male Rats ◽  
Control Group ◽  
Model Group

Abstract: Objective: To investigate the effect of tripterine on Notch signaling pathway in renal tissue of IgA nephropathy rats. Methods: SD male rats were divided into the control group, IgAN nephropathy model group, benazepril group, 1mg/kg/d tripterine intervention group and 10mg/kg/d tripterine intervention group according to the random number table method, with 10 rats in each group. The urinary sediment and 24-hour urinary protein quantity were detected by conventional methods. The expressions of Notch1, Jagged1, Hes1 and Hey1 in renal tissue of rats were detected by real-time fluorescent quantitative PCR. Results: IgA nephropathy model was successfully established. The hematuria and proteinuria in model group were higher than those of control group (P<0.05). The expressions of Notch1, Jagged1, Hes1 and hey1 in kidney tissue of IgA nephropathy rats were significantly increased (P<0.05). Compared with the model group, hematuria and proteinuria in tripterine intervention group were alleviated. The expressions of Notch1, Jagged1, Hes1 and Hey1 in rat renal tissue were decreased (P<0.05). Moreover, the expressions of Notch1, Jagged1, Hes1 and Hey1 in renal tissue of rats in 10mg/kg/d tripterine intervention group were decreased (P<0.05). Conclusion: Tripterine can decrease the levels of hematuria and proteinuria in IgA nephropathy rats. The expression of Notch signaling pathway in IgA nephropathy rats is increased by the down-regulation of tripterine, suggesting that tripterine has a certain therapeutic effect on IgA nephropathy rat. And its role may be realized through this signal pathway so as to provide the new mentality for the diagnosis and treatment of IgA nephropathy.

scholarly journals Impact of goal-directed hemodynamic management on the incidence of acute kidney injury in patients undergoing partial nephrectomy: a pilot randomized controlled trial

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qiong-Fang Wu ◽  
Hao Kong ◽  
Zhen-Zhen Xu ◽  
Huai-Jin Li ◽  
Dong-Liang Mu ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Partial Nephrectomy ◽  
Controlled Trial ◽  
Intervention Group ◽  
Kidney Injury ◽  
Control Group ◽  
Hemodynamic Management ◽  
Randomized Controlled ◽  
Renal Hilum ◽  
Pilot Randomized Controlled Trial

Abstract Background The incidence of acute kidney injury (AKI) remains high after partial nephrectomy. Ischemia-reperfusion injury produced by renal hilum clamping during surgery might have contributed to the development of AKI. In this study we tested the hypothesis that goal-directed fluid and blood pressure management may reduce AKI in patients following partial nephrectomy. Methods This was a pilot randomized controlled trial. Adult patients who were scheduled to undergo partial nephrectomy were randomized into two groups. In the intervention group, goal-directed hemodynamic management was performed from renal hilum clamping until end of surgery; the target was to maintain stroke volume variation < 6%, cardiac index 3.0–4.0 L/min/m2 and mean arterial pressure > 95 mmHg with crystalloid fluids and infusion of dobutamine and/or norepinephrine. In the control group, hemodynamic management was performed according to routine practice. The primary outcome was the incidence of AKI within the first 3 postoperative days. Results From June 2016 to January 2017, 144 patients were enrolled and randomized (intervention group, n = 72; control group, n = 72). AKI developed in 12.5% of patients in the intervention group and in 20.8% of patients in the control group; the relative reduction of AKI was 39.9% in the intervention group but the difference was not statistically significant (relative risk 0.60, 95% confidence interval [CI] 0.28–1.28; P = 0.180). No significant differences were found regarding AKI classification, change of estimated glomerular filtration rate over time, incidence of postoperative 30-day complications, postoperative length of hospital stay, as well as 30-day and 6-month mortality between the two groups. Conclusion For patients undergoing partial nephrectomy, goal-directed circulatory management during surgery reduced postoperative AKI by about 40%, although not significantly so. The trial was underpowered. Large sample size randomized trials are needed to confirm our results. Trial registration Clinicaltrials.gov identifier: NCT02803372. Date of registration: June 6, 2016.

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.

scholarly journals Fasudil ameliorated liposaccharide-induced acute kidney injury in mice by inhibiting NLRP3

2021 ◽  
Vol 20 (10) ◽  
pp. 2055-2062
Author(s):  
Xueqian Li ◽  
Chengzhi Zhao
Keyword(s):  
Acute Kidney Injury ◽  
Treatment Group ◽  
Cell Growth ◽  
Mesangial Cells ◽  
Kidney Injury ◽  
Inflammatory Factors ◽  
Control Group ◽  
Model Group ◽  
Blank Control Group ◽  
Tissue Homogenates

Purpose: To determine the influence of fasudil on LPS-mediated acute kidney injury (AKI) in mice.Methods: Healthy C57 mice (n = 140) of largely similar weight were used in this study. They were assigned to a treatment group (n = 40), a model group (n = 50), and a blank control group (n = 50). Mice in treatment and model groups were injected with lipopolysaccharide (LPS). In the treatment group, each mouse was injected intravenously with fasudil daily before the establishment of the mouse model of AKI. All mice were sacrificed 6 h after establishing the AKI model. Portions of the kidney from mice were used for preparation of tissue homogenates, while the remaining portions were subjected to primary culture. Transformed C3H Mouse Kidney-1 (TCMK1) and mesangial cells from mouse glomeruli (SV40-MES-13) cells were used for assays of cell growth and apoptosis. Blood samples were alsocollected from the mice. Thereafter, the levels of blood urea nitrogen (BUN) and creatinine (Cr) in kidney homogenates of the three groups were determined. Moreover, levels of NLRP3, nuclear factor kappa-B (NF-κB), toll-like receptor 4 (TLR4), tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β in the homogenates and blood were assayed. Cell growth and apoptosis were also measured.Results: The treatment group and model group showed higher levels of BUN and Cr than the control group, with a higher level observed in model mice than in the treatment mice. There were significantly higher relative levels of NF-κB, NLRP3 and TLR4 in treatment and model groups than in controls, with a higher level observed in model mice than in treatment mice. There were significantly higher concentrations of inflammatory factors in treatment and model mice groups than in control mice, with higher levels observed in model mice than in treatment mice. The TCMK1 and SV40-MES-13 cells in the two groups showed slower cell growth and stronger apoptosis than those in control group (p < 0.05).Conclusion: Fasudil relieved LPS-mediated AKI in mice by suppressing TLR4/NF-κB signal pathway and lowering NLRP3. Thus, fasudil has potential as a new adjunctive agent for the treatment of AKI.

Therapeutic Effect of Glycyrrhizin Arginine Salt on Rat Cholestatic Cirrhosis and its Mechanism

2018 ◽  
Vol 46 (05) ◽  
pp. 1111-1127 ◽  
Author(s):  
Huan Zhang ◽  
Yajun Lin ◽  
Yongzhan Zhen ◽  
Gang Hu ◽  
Xu Meng ◽  
...  
Keyword(s):  
Matrix Metalloproteinases ◽  
Therapeutic Effect ◽  
Group Treatment ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Water Model ◽  
Control Group ◽  
High Dose ◽  
Model Group ◽  
Duct Ligation

To investigate the therapeutic effect of glycyrrhizin arginine salt on rat cholestatic cirrhosis, we subjected male Sprague Dawley rats to common bile duct ligation for 14 days and treated them with distilled water (model group), arginine, or a low or high dose of glycyrrhizin arginine salt by gavage. A sham-operated group was used as a control group. Treatment with glycyrrhizin arginine salt substantially improved animal growth rates, reduced the ratio of liver weight to body weight and decreased total bilirubin, aspartate aminotransferase, 8-isoprostane and malondialdehyde compared with the values measured in the model group. The progress of liver fibrosis, as detected by hematoxylin and eosin and Masson’s trichrome staining, was slower in the glycyrrhizin arginine salt groups than in the model group or the arginine group. Reductions of bile salt pool size, hepatic hydroxyproline content and fibrosis score were also seen in the glycyrrhizin arginine salt groups compared with the model group. Furthermore, glycyrrhizin arginine salt significantly reduced the expression of transforming growth factor [Formula: see text]1 (TGF-[Formula: see text]1), [Formula: see text]-smooth muscle actin, tumor necrosis factor-[Formula: see text] and matrix metalloproteinases 2 and 9. Glycyrrhizin arginine salt also inhibited the expression of [Formula: see text]-SMA and matrix metalloproteinases 2 and 9 in response to TGF-[Formula: see text]1 in LX-2 cells and primary rat hepatic stellate cells and mitigated the cytotoxicity induced by rat bile in HepG2 cells and primary rat hepatocytes.

scholarly journals Histologic study of use of microfibrillar collagen hemostat in rat dental sockets

2003 ◽  
Vol 14 (1) ◽  
pp. 12-15 ◽  
Author(s):  
Natasha Magro-Érnica ◽  
Osvaldo Magro-Filho ◽  
Idelmo Rangel-Garcia
Keyword(s):  
Control Group ◽  
Image Analysis System ◽  
Bone Area ◽  
Central Incisor ◽  
Histologic Study ◽  
Socket Healing ◽  
Hematoxylin And Eosin ◽  
Analysis System ◽  
The Right ◽  
Qualitative Analyses

The aim of this paper was to evaluate if the placement of microfibrillar collagen hemostat (MCH) into a dental socket interfered with healing. General anesthesia was administered to 30 adult male Albinus Wistar rats and the maxillary right central incisor was extracted. In the control group after each tooth was extracted, the socket was sutured. In the MCH group after each tooth was extracted, MCH was placed into the socket before suturing. Postoperatively, 5 animals were sacrificed from each group at 7, 21 and 28 days. The right maxilla was removed from each animal and histologic slides were stained with Masson's trichromic and hematoxylin and eosin. Quantitative and qualitative analyses were done. The percentage of bone area in the dental socket was quantified using the Image Lab 98 image analysis system. The bone area formation for the control and MCH groups was: 8.1% and 3.3% at 7 days, 34.4% and 33% at 21 days and 41% and 41.3% at 28 days, respectively. We concluded that MCH interferes with the beginning of dental socket healing but does not interfere with the final healing of the dental socket.

scholarly journals Effect of Qingxin Kaiqiao Fang on Hippocampus mRNA Expression of the Inflammation-Related Genes IL-1β, GFAP, and Aβin an Alzheimer’s Disease Rat Model

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Dan-Dan Mao ◽  
Wen-Yu Yang ◽  
Yan Li ◽  
Jian-Wei Lin ◽  
Shi-Yu Gao ◽  
...  
Keyword(s):  
Rat Model ◽  
Particle Deposition ◽  
Therapeutic Potential ◽  
Interleukin 1 ◽  
Control Group ◽  
Model Group ◽  
Sprague Dawley ◽  
Amyloid A ◽  
Sprague Dawley Rats ◽  
High Doses

Objective. To investigate the effects of QKF on expression of amyloid-beta (Aβ), interleukin-1 beta (IL-1β), and glial fibrillary acidic protein (GFAP) using a rat model of AD.Materials and Methods. Fifty-six male Sprague-Dawley rats were randomly divided into seven groups (eight rats each): control group, sham-operated group, AD model group, groups of AD rats administered with low, medium, and high doses of QKF, and the donepezil group. AD was established by bilateral injection ofβ-amyloid (Aβ) 1–40 into the hippocampus. Two days after AD was established, drugs were administered by gavage. After 14 days of treatment, we used RT-PCR, Western blotting, and immunohistochemistry to measure the transcript expression and protein abundance of Aβ, IL-1β, and GFAP, and methenamine silver staining was used to detect amyloid protein particle deposition.Results. Compared to the control group, the rats from the AD model group showed significantly greater expression levels of Aβ, IL-1β, and GFAP. However, these differences in expression were abolished by treatment with QKF or donepezil.Conclusion. QKF possesses therapeutic potential against AD because it downregulated Aβ, IL-1β, and GFAP in the hippocampus of AD rats. Future studies should further examine the mechanisms through which QKF produces its effects and the consequences of long-term QKF administration.

scholarly journals Islet Cryopreservation: Improved Recovery following Taurine Pretreatment

2001 ◽  
Vol 10 (3) ◽  
pp. 247-253 ◽  
Author(s):  
Anandwardhan A. Hardikar ◽  
Makarand V. Risbud ◽  
Claude Remacle ◽  
Brigitte Reusens ◽  
Joseph J. Hoet ◽  
...  
Keyword(s):  
Islet Cells ◽  
Radical Scavenging ◽  
The Body ◽  
Control Group ◽  
Image Analysis System ◽  
Islet Mass ◽  
Normal Glucose ◽  
Ethanesulfonic Acid ◽  
Analysis System ◽  
Digital Image Analysis System

Simple and efficient freezing methods with maximal postthawing recovery form the basis of ideal cryopreservation. Taurine (2-amino ethanesulfonic acid), an end-product of sulphur amino acid metabolism, is one of the most abundant free amino acids in the body. The membrane stabilizing, free radical scavenging, and osmoregulatory roles of taurine have been well documented. We studied the effect of physiological and supra-physiological concentrations (0.3 and 3.0 mM) of taurine on islet cryopreservation. Islet viability on cryopreservation was significantly improved in both the taurine-treated groups (91.9 ± 2.3% in 0.3 mM and 94.6 ± 1.58% in 3.0 mM group, p < 0.05) compared with the controls (85.7 ± 3.4%). Loss of peripheral islet cells was highly reduced in the taurine group, as examined under phase contrast and quantified by islet morphometric analysis (p < 0.05) using a digital image analysis system. Taurine-treated islets showed significant reduction in lipid peroxidation (0.905 and 0.848 nM MDA/μg protein for 0.3 and 3.0 mM taurine, respectively, p < 0.05) compared with control (1.307 nM MDA/μg protein) islets. In all, 500 islet equivalents (IE) of treated or control group islets were transplanted to BALB/c mice rendered diabetic with STZ. All animals showed a normal glucose clearance following a glucose load. Graft functionality was confirmed by normoglycemia (fasting plasma glucose: fpg < 150 mg/dl) after transplantation and reappearing hyperglycemia (fpg > 200 mg/dl) following removal of the graft. Suboptimal islet transplantation using 250 IE suggests that the grafted islet mass was inadequate for diabetes reversal. In addition, no significant differences were observed in the islet insulin content between the three groups following cryopreservation of the islets at −196°C. Our studies indicate that taurine pretreatment and its continued presence during islet cryopreservation improves the postthawing viable recovery of islets.

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