Effect Of Yiqi Huayu Huatan Decoction On Expression Of KLF15, HMGB1, NF-?B And Its Downstream Inflammatory Factors In Rats With UUO-induced Renal Interstitial Fibrosis

Objective:To observe the effect of Yiqi Huayu Huatan Decoction(YHHD)on UUO-induced renal interstitial fibrosis in rats and to investigate the possible mechanism.Methods:Female SD rats(n=48)were randomly divided into sham operation group,model group,telmisartan group,and Yiqi Huayu Huatan Decoction low-,middle-and high-dose group,with 8 rats in each group.Except of sham operation group,the model rats were established by ligating left ureter.The rats in sham operation group and model group were treated with equal volume of normal saline,another groups were treated with the corresponding decoction once a day.After 12 weeks,the rats were sacrificed.The serum samples were collected for determining the concentrations of Cys-C and UA.The morphological changes of the renal tissue were observed by PAS staining.The collagen fiber was observed by Masson staining.The mRNA expression of KLF15,HMGB1,NF-?B,I?B,MCP-1,IL-1?,TNF-?,FN,ColI and Col? was detected by real-time PCR.The protein expression of KLF15,HMGB1,NF-?B was detected by Western blotting.The protein expression of MCP-1 was determined by the method of immunohistochemistry.Results:Compared with sham group,the deposition rate of collagen fibers and the concentration of Cys-C in model group were significantly increased(P<0.05),the mRNA and protein expression of KLF15 were significantly down-regulated(P<0.05),while the mRNA expression of HMGB1,NF-?B,I?B,MCP-1,IL-1?,TNF-?,FN,ColI,Col? and the protein expression of HMGB1,NF-?B,MCP-1 were significantly up-regulated(P<0.05).Compared with model group,the deposition rate of collagen fibers in YHHD middle-,high-dose groups and the telmisartan group was significantly decreased(P<0.05),with down-regulating the protein expression of HMGB1,NF-?B and the mRNA expression of IL-1?,TNF-? significantly(P<0.05);the protein expression of KLF15 was significantly up-regulated in YHHD high-dose group and the telmisartan group(P<0.05),while the protein expression of MCP-1 and the mRNA expression of FN were significantly down-regulated(P<0.05);the mRNA expression of KLF15 was significantly up-regulated in YHHD high-dose group(P<0.05),while the mRNA expression of MCP-1,ColI and ColIV was significantly down-regulated(P<0.05);the mRNA expression of NF-?B,I?B were significantly down-regulated and the concentration of Cys-C wassignificantly decreased in each dose of YHHD groups and telmisartan group(P<0.05).No significant difference of UA level among the groups was observed.Conclusion:Yiqi Huayu Huatan Decoction could alleviate renal interstitial fibrosis in a dose-dependent manner,and YHHD at high dose showed the most obvious effect.The mechanism may be associated with the up-regulation of KLF15 and the down-regulation of HMGB1,NF-?B and its downstream inflammation related factors in the renal tissue.