Study On Activation Of Wnt4/β-catenin Signaling Pathway Promotes Renal Fibrosis And Effects Of Atorvastatin Intervention Referred To UUO Rats

Objective: To observe the expression of Wnt4/β-catenin signaling pathway and the effects of atorvastatin intervention on the pathway in renal tissue of unilateral ureteral obstruction(UUO) rats, aim to explore the possible mechanism and function of atorvastatin involved in anti-fibrosis. Methods:The 60 Sprague-Dawley(SD) rats with half males and half females were divided randomly into 3 groups: the sham group(Sham), the model group(UUO) and the atorvastatin group(Ato), and was equipped with 7 days(7 d) and 14 days(14 d) in each group. The atorvastatin group had been treated with 2 m L the suspension of normal saline and atorvastatin(10 mg/kg/d) by daily gastric gavage, from three days before the UUO operation to the day of has been sacrificed, the Sham and model group were treated with the same dose normal saline in an identical fashion. Six rats of each group were sacrificed respectively at 7 d and 14 d after surgery. The pathological changes in renal tissue were detected using HE, and PAS and Masson staining. In addition, immunohistoche-mistry staining were employed to detect the expression of Wnt4 and β-catenin protein in renal tissue. And Western blotting were used to detect the expression of Wnt4, β-catenin, p-GSK-3β, GSK-3β, E-cadherin, α-SMA and collagenⅠprotein in the rats renal tissue. Results: Compared with the sham group, the typical morphologic changes were presenting in the model group, the expression of Wnt4 and β-catenin protein was increased significantly(P<0.05), with increase of p-GSK-3β, α-SMA and collagenⅠprotein(P<0.01), while the levels of E-cadherin protein was obvious decreased(P<0.01), and the expression of GSK-3β protein was no significant change in different groups(p>0.05).Compared with the model group, the renal fibrosis were obviously relief in the atorvastatin group, accompanied by the levels of Wnt4, β-catenin, p-GSK-3β, α-SMA and collagenⅠprotein expression was obvious decreased(p<0.05), and the expression of E-cadherin protein was evident increased(p<0.05), the levels of GSK-3β protein was undifferentiated in each group(p>0.05). The difference of renal fibrosis lesions and check indexes of every item were not statistically significant between males rate and females rats at the same group(p>0.05). Conclusion: The activation of the Wnt4/β-catenin signaling pathway promoted renal fibrosis. And the protective effect of atorvastatin on renal fibrosis, which relieved the fibrosis and alleviated the accumulation of ECM, maybe relate to inhibiting the activation and transduction of Wnt4/β-catenin signaling pathway.