| Objective: This research observed the infulence of Chailing decoction oninflammatory factors in chronic cyclosporine A nephropathy rats. Explore themechanism and protection of Chailing decoctionon on chronic nephrotoxicitywith CsA and provide the evidence for the clinical application.Method: Healthy40female Sprague-Dawley(SD) rats weight200g wereused in this study. After7days to adapt, rats randomly divided into4groups:Control group (A group), Model group (B group), Valsartan group (C group),Chailing Decoction group (D group). The rats with chronic nephropathy wasinduced by CsA with30mg·kg-1·d-1orally. Same dose of olive oil was given inControl group. Meanwhile treated groups were respectively given valsartan10mg·kg-1·d-1and chailing decoction3g·kg-1·d-1orally.The urine was collected inmetabolic cages every weekend. Four weeks later, the kidneys and blood wereharvested. Conservation of samples of serum, and plasma samples to be usedfor blood urea nitrogen (BUN), serum creatinine (Scr), and creatinine cearancerate (Ccr). Kidneys were fixed by10%paraformaldehyde for pathologicalexamine. Monocyte chemoattractant protein-1(MCP-1), tumor necrosisfactor-α (TNF-α) were detected by immunohistochemistry. The mRNA ofMCP-1and TNF-α were detected by reverse transcriptase polymerase chainreaction (RT-PCR).Result:①Renal function: Compared with the control group, blood ureanitrogen (BUN) and serum creatinine(Scr) were increased significantly(P<0.01). While creatinine clearance rate (Ccr) was decreased in the modelgroup (P<0.01). After treatment, blood urea nitrogen(BUN) and serumcreatinine(Scr) were significantly lower while creatinine clearance rate (Ccr)wassignificantly higher (P<0.05) in both Val group and Chailingdecoctiongroup.②Pathologic changes: There was no change in control group.In model group, the structure of tubules were disorded, renal tubular epithelial cells were denatured, necrosis and even shed. The renal tubular basementmembrane was thickened and wrinkled even disruptioned. Meanwhile renalinterstitial space was widened, and there were a large number of inflammativecells and collagen infitrationed. All the above accorded with tupical renalinterstitialfibrosis. In addtion, there were a great improvement in both Valgroup and Chailing group.③Renal interstitial fibrosis assessment: Comparedwith the control group, the index of renal interstitial fibrosis were increasedsignificantly in the model group (P<0.05). After treatment, the index of renalinterstitial fibrosis were significantly lower in both Val group and Chailingdecoction group (P<0.05).④The count of renal interstitial inflammatory cells:Compared with the control group,the number of inflammatory cells wasincreased significantly in the model group (P<0.05). After treatment, thenumber of inflammatory cells was significantly lower in both Val group andChailing decoction group (P<0.05). Except control group, the number ofinflammatory cells was significantly heighest in cortical area, then boundaryarea, and lowest in medulla areas (P<0.05).⑤The expression of MCP-1andTNF-α: Compared with the control group, the expression of MCP-1andTNF-α were increased significantly in the model group (P<0.05). Aftertreatment, the expression of MCP-1and TNF-α were significantlydown-regulated in both Val group and Chailing decoction group (P<0.05).MCP-1mainly expressed in tubular epithelial cells. TNF-α was mainlyexpressed in tubular epithelial cell.⑥RT-PCR detection of MCP-1mRNA andTNF-αmRNA: Compared with the control group, the expression of MCP-1mRNA and TNF-α mRNA were increased significantly in the model group(P<0.05). After treatment, the expression of MCP-I and TNF-α weresignificantly down-regulated in both Val group and Chailing decoction group(P<0.05). There is no significantly difference between these two treatmentgroups.⑦: the correlation analysis between inflammatory factors and fibrosis:there is a positive correlation between both MCP-I and TNF-α with fibrosis,the correlation coefficient respectively is0.755(P<0.05) and0.812(P<0.05). Conclusion:1. In this research, healthy40female SD rats which were treated withCsA30mg·kg-1·d-1and ordinary diet4weeks were used to built chroniccyclosporine A nephropathy rats models. In the end, the rats showed kidneyfailure, such as BUN/Scr rising, focal interstitial fibrosis, as well asinflammatory cells infiltrating etc.2. Chailing decoction has the function of delaying the progression ofkidney narrowing, decreasing BUN/Scr, increasing Ccr to protect the kidneyfunction.3. Chailing decoction plays a role in inhibit the infiltration ofinflammatory cells.4. Chailing decoction plays a role in down-regulating the over expressionof MCP-1and TNF-α, improving the glomerular filtration rate and protectingthe function of kidney, so as to retard the progress of chronic kidney toxicity5. Chailing decoction plays a role in down-regulating the over expressionof MCP-1mRNA and TNF-α mRNA. |
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