Effect Of Fushenggong Decoction On P38MAPK Signaling Pathway In Rats With Chronic Renal Failure

ObjectiveThe aim of the present study was to investigate the effect of Fushengong decoction on the expression of p38 MAPK signaling pathway and related inflammatory cytokines in CRF rats in inflammatory responding.Combining with the results of previous experiments,the possible mechanism of Fushengong decoction in the treatment of chronic renal failure was further explored.It provides a reliable experimental basis for the development of a Chinese patent medicine with clear mechanism,safe and effective treatment for chronic renal failure.MethodsEleven rats were randomly selected from a total of fifty-five male Sprague-Dawley rats as the normal control group,and the rest were fed with 0.5% adenine feed to create the experimental pathological model of CRF,and after 3 weeks,the model was successfully constructed by tail vein blood sampling of 4 rats and 1 normal rat were randomly selected.After successful modeling,the rats were randomly divided intolow,medium and high Fushengong decoction dose group and model group(11 in each group),were changed to normal feeding.The model group and the normal group received 0.9% NaCL by 20ml/kg.d for 30 days.The Fushengong decoction in each dose group received Fushengong decoction at a ratio matched with the weight of 4,8,16 g/kg of the original medicinal herbs respectively,once a day for 30 days.After the intervention,all the rats received abdominal anesthesia,cardiac blood collection,separation of abdominal tissue,and the bilateral kidneys were exposed,renal fascia were stripped,the renal arteriovenous and the ureters were fixed by hemostatic forceps,the kidneys were separated out and stored by 4% paraformaldehyde and liquid nitrogen.HE and Masson staining were used to observe the changes in histomorphology and collagen.The expression of MCP-1 and macrophage(CD68)was observed by immunohistochemistry;Western blot was used to detect the expression of p-p38 MAPK,p38MAPK and TGF-β1 protein.The expression of TNF-αmRNA and IL-6 mRNA was detected by RT-PCR.ResultsCompared with the normal group,the positive counts of MCP-1 and CD68 macrophages in the CRF model group were significantly increased(p<0.05),and the expressions of p-p38 MAPK,TGF-β1 protein,TNF-αmRNA and IL-6 mRNA were significantly increased(p<0.05).Compared with the model group,the positive counts of MCP-1 and CD68 macrophages in the Fushengong decoction dose group were significantly decreased(p<0.05),and the expressions of p-p38 MAPK,TGF-β1 protein and TNF-α,IL-6 mRNA were significantly decreased(p< 0.05).ConclusionFushengong decoction can effectively improve the expression of renal interstitial inflammatory cell infiltration and related inflammatory cytokines in rats with chronic renal failure,thereby alleviating the inflammatory reaction of renal tissue and delaying the progression of CRF.The intervention mechanism may be related to inhibition of the activation of p38 MAPK signal transduction pathway and reduction of expression of downstream related cytokines MCP-1 and TGF-β1,etc.