Zhen-wu-tang protects against podocyte injury in rats with IgA nephropathy via PPAR gamma/NF-kappa B pathway

Zhen-wu-tang (ZWT) has been widely applied in chronic kidney diseases. However, the mechanism of ZWT remains unclear. Peroxisome proliferator-activated receptors-gamma (PPAR gamma) is known as a protective factor for podocyte and kidney function. This study is aimed to investigate the protective effects of ZWT on IgA nephropathy (IgAN) in rats against podocyte injury and the underlying mechanism related to PPAR gamma. IgAN model rats were induced by administering bovine serum albumin, lipopolysaccharide, and carbon tetrachloride. ZWT at two doses and GW9662 (PPAR gamma antagonist) was administered once daily for 4 weeks respectively. Cultured podocyte induced by LPS were used to evaluate the podocyte-protective effect and related mechanism of ZWT in vitro. Results showed that ZWT observably reduced proteinuria and hematuria excretion, as well as the levels of blood urea nitrogen, serum creatinine, serum uric acid, low-density lipoprotein cholesterol, total cholesterol and triglycerides, but increased the contents of high-density lipoprotein cholesterol, ameliorating renal function and hyperlipidemia state in IgAN rats. Besides, both ZWT administration groups alleviated kidney pathological lesion, macrophage infiltration, IgA and C3 deposition in glomeruli. To further demonstrate the protective effects of ZWT, we found that podocyte damage was markedly ameliorated with ZWT treatments in IgAN rats and LPSinduced podocyte injury model by suppressing the expressions of desmin, reducing podocyte apoptosis and augmenting nephrin and podocin levels. Moreover, ZWT inhibited the phosphorylation of NF-kappa B and I kappa B alpha, simultaneously upregulated PPAR gamma. However, GW9662 made no difference in all the above effects compared to the model group, and was reversed by ZWT in vitro study. In conclusion, these results demonstrated that ZWT ameliorated IgAN-induced podocyte injury via upregulation PPAR gamma and the underlying mechanism might involve the inhibition of NF-kappa B pathway.