Effects Of Manshenkangning In Signaling Pathway Of Wnt/β-catenin In Renal Interstitial Fibrosis In UUO Rats

OBJECTIVE：To observe the effect and mechanism of manshenkangning in signalingpathway of Wnt/β-catenin in renal interstitial fibrosis in UUO rats.METHODS：After the one week of the adaptability feeding,60male wistar rats wererandomly divided into normal group, sham operative group, model, alsartan control groups,manshenkangning group of high-dose, and low-dose groups according to body weight, eachgroup of10. After intraperitoneal pentobarbital anesthesia, the left kidney and ureter of modelgroups and treatment groups were exposed through an abdominal incision under sterileenvironments. In order to prevent retrograde urinary tract infection, the left ureter was ligatedwith monofilament4–0polypropylene suture at two points and cut between the ligatures, andthen close the abdominal cavity. Sham animals underwent identical surgical procedures, butthe left ureter was not obstructed.Postoperative intraperitoneal injection of penicillin (100,000units/rat) is used to prevent infections, for three consecutive days. Drugs were administeredfrom the day before operation, treatment group rats were given manshenkangning with highdose（30g.kg-1.d-1) and low dose（15g.kg-1.d-1) and valsartan（8mg.kg-1.d-1）via intragastricadministration, respectively. The rest group rats were given an equal volume of normal saline.Each group of intragastric administration for12consecutive days. All rats were sacrificedafter12days, and kidney tissue were collected. The pathological changes of renal tissue wereobserved by HE and Masson stain. Immunohistochemistry stain was used to measure the levelof expression of E-cadeherin and β-catenin. Wnt4、β-catenin、ColⅢ mRNA was detected byReal-time quantitative PCR.RESULTS：Valsartan and manshenkangning can reduce renal interstitial fibrosis in UUO rats.HE and Masson stain showed that there was no change in normal and sham group. Comparedwith the model groups, pathological lesions of the left kidney of manshenkangning andvalsartan group were significantly improved.The situation of renal tubular atrophy, collapse orexpansion has improved, fewer inflammatory cell infiltration, tube or protein cast in somerenal tubules was rare and the area of renal interstitial fibrosis was narrowed. Real-time PCRshowed that compared with the model groups, the Wnt4, β-catenin and ColⅢ mRNA indifferent treatment groups expression levels declined markedly (P<0.01).Immunohistochemistry revealed that compared with the model group, the protein expression of β-catenin in the treated group was noticeably reduced(P<0.01) and the E-cadeherin proteinexpression is markedly elevated (P<0.05).CONCLUSION：Wnt/β-catenin signaling pathways in the renal interstitial fibrosis in UUOrats are activated; Manshenkangning can inhibits Wnt/β-catenin signaling pathways in therenal interstitial fibrosis in UUO rats, down-regulated expression of β-catenin andup-regulated expression of E-cadherin; Manshenkangning can reduce renal interstitial fibrosis,reduced expression of ColⅢ, this process can be achieved by inhibiting Wnt/β-cateninsignaling pathway.