Protective Effect of Xiayuxue Tang on Renal Fibrosis Rats Based on Wnt/β-catenin and TGF-β1/Smad Signal Pathway / 中国实验方剂学杂志

ABSTRACT

Objective:To study the protective effect of Xiayuxue Tang on adenine-induced renal fibrosis model in rats and its impact on Wnt/<italic>β</italic>-catenin and transforming growth factor <italic>β</italic>₁（TGF-<italic>β</italic>₁）/Smad signal pathway. Method:A total of 50 SPF-grade male SD rats were randomly divided into 5 groups： the normal group， the model group， the losartan group （9 mg·kg^-1） and low and high dose （2.43，4.86 g·kg^-1） of Xiayuxue Tang groups. The rat model of renal fibrosis was established by ig administration adenine （250 mg·kg^-1） for 24 consecutive days. The rats were then given the corresponding drugs for 30 consecutive days. The levels of serum creatinine（SCr） and blood urea nitrogen （BUN） were measured by enzyme-linked immunosorbent assay（ELISA）. The histopathological changes of renal tissues in rats were observed by hematoxylin and eosin （HE） staining. The collagen deposition in rat renal tissue was observed by Masson staining； the protein expression levels of Wnt5a， Wnt5b， <italic>β</italic>-catenin， TGF-<italic>β</italic>₁， Smad4， Smad7 in renal tissue were detected respectively by immunohistochemistry（IHC） and Western blot. Result:Compared with the normal group， the results of each experimental group showed that SCr and BUN levels significantly increased in the model group （<italic>P</italic><0.01）. SCr and BUN levels decreased significantly after the intervention with the Xiayuxue Tang （<italic>P</italic><0.01）. Compared with the normal group， HE and Masson staining results showed that rats in the model group had severe renal interstitial damage and massive deposition of renal interstitial collagen. The renal interstitial tubule injury was relieved after the intervention with the Xiayuxue Tang， and the renal interstitial collagen deposition decreased. The results of IHC and Western blot showed that compared with the normal group， the expressions of Wnt5a， <italic>β</italic>-catenin， TGF-<italic>β</italic>₁ protein in the kidney of rats up-regulated （<italic>P</italic><0.01）， while the expressions of Wnt5b and Smad7 protein down-regulated （<italic>P</italic><0.01）. After the intervention with Xiayuxue Tang， the expressions of Wnt5a， <italic>β</italic>-catenin， TGF-<italic>β</italic>₁ protein down-regulated （<italic>P</italic><0.01）， while the expressions of Wnt5b and Smad7 protein up-regulated（<italic>P</italic><0.01）. There was no significant difference between the low-dose and high-dose groups with Xiayuxue Tang. Conclusion:Xiayuxue Tang has the protective effect on RIF rats induced by adenine， and its mechanism is related to the inhibition of Wnt/<italic>β</italic>-catenin and TGF-<italic>β</italic>₁/Smad signal pathway.