基于TGF-β1/Notch1/p53信号通路探讨加味五子衍宗丸对高尿酸血症诱导足细胞损伤的影响OA

Objective It is to explore the mechanism of modified Wuzi Yanzong Pill in attenuating podocyte injury in-duced by hyperuricemia in rats via the transforming growth factor-β1(TGF-β1)/Notch1/p53 signaling pathway.Methods Sixty SPF-grade male SD rats were randomly divided into normal group,model control group,allopurinol group,and low-dose,medium-dose,and high-dose groups of modified Wuzi Yanzong Pill,with 10 rats in each group.The rats of all groups except for the normal group were prepared to establish models of hyperuricemia.The low-dose,medium-dose,and high-dose groups of modified Wuzi Yanzong Pill were given modified Wuzi Yanzong Pill0.72 g/(kg·d),1.44 g/(kg·d),2.88 g/(kg·d)via gavage,respectively,the allopurinol group was given allopurinol 25 mg/(kg·d)via gavage,the model group and normal group were given equal volume of normal saline via gavage,all once daily,continuously treated for 8 weeks.The binding of modified Wuzi Yanzong Pill with TGF-β1 protein was verified by Biocore experiment,the levels of serum uric acid(SUA),serum creatinine(SCr),blood urea nitrogen(BUN),and albumin-to-creatinine ratio(ACR)were measured according to the kit instructions,the morphology of renal tissue was observed by HE staining,the protein ex-pressions of TGF-β1,Notch1,p53,and Nephrin in renal tissue were detected by immunohistochemistry,the mRNA ex-pressions of TGF-β1,Notch1,p53,and Nephrin in renal tissue were detected by qRT-PCR.Results Modified Wuzi Yan-zong Pill had a molecular binding with TGF-β1.Compared with the normal group,the levels of SUA,SCr,BUN and ACR were all significantly increased in the model group(all P<0.05);glomerular atrophy,edema of proximal and distal con-voluted tubules,as well as inflammatory cell infiltration accompanied by cellular vacuolization were found in the model group;the positive expression scores and relative mRNA expressions of TGF-β1,Notch1,and p53 in renal tissue were all significantly increased(all P<0.05),while the positive expression score and relative mRNA expression of Nephrin in re-nal tissue were both significantly reduced(all P<0.05).Compared with the model group,the levels of SUA,SCr,BUN(except for the low-dose group of modified Wuzi Yanzong Pill)and ACR were all significantly decreased in the medicated groups(all P<0.05);the morphologic changes in renal tissue were attenuated at different degrees in the medicated groups;the positive expression scores in renal tissue were all significantly decreased(all P<0.05),while the positive ex-pression scores of Nephrin in renal tissue of the allopurinol group and high-dose group of modified Wuzi Yanzong Pill were all significantly increased(all P<0.05);the relative mRNA expressions of TGF-β1,Notch1,and p53 in renal tissue of the medicated groups(all P<0.05),while the relative mRNA expressions of Nephrin in renal tissue of all medicated groups were all significantly increased(all P<0.05).The improvements of these indicators were the most significant in the high-dose group of modified Wuzi Yanzong Pill when compared between the medicated groups.Conclusion Modified Wuzi Yanzong Pill can attenuate podocyte injury induced by hyperuricemia in rats via regulating the TGF-β1/Notch1/P53 signaling pathway.