Huangqi decoction inhibits hyperglycemia-induced podocyte apoptosis by down-regulated Nox4/p53/Bax signaling in vitro and in vivo

黄芪汤在体内外通过下调 Nox4/p53/Bax 信号抑制高血糖诱导的足细胞凋亡

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作者:Zezheng Li, Wenjuan Deng, Aili Cao, Yingjun Zang, Yunman Wang, Hao Wang, Li Wang, Wen Peng

Background

Podocyte dysfunction is associated with the progression of diabetic nephropathy (DN). Huangqi decoction (HQD), a traditional Chinese medical formula, has been used to improve diabetes-related syndrome in China. The present study was to investigate the protective effect of HQD on podocyte apoptosis and the underlying molecular mechanism.

Conclusion

Collectively, we provide further evidence that HQD had a renoprotective effect in preventing podocyte apoptosis, which was mediated at least in part by down-regulation of Nox4/p53/Bax signaling.

Methods

Podocyte was used to measure the efficacy of HQD on cell apoptosis, activities of NADPH oxidases, ROS generation and mitochondrial membrane potential (MMP), and the activation of Nox4/p53/Bax signaling pathway with HQD treatment were also investigated in vitro. Renal pathological morphology, renal function, podocyte apoptosis and Nox4/p53/Bax signaling pathway were investigated with STZ-induced diabetic mice in vivo.

Results

HQD increased the cell proliferation and MMP level, while the ROS production and activities of NADPH oxidases were decreased. Meanwhile, Nox4/p53/Bax signaling was down-regulated. Contrarily, overexpression of Nox4 or p53 significantly abolished those efficacies of HQD. Accordingly, in vivo study showed that the progressive albuminuria, glomerulosclerosis and loss of podocytes were significantly alleviated with HQD treatment in diabetic mice, which paralleled by the marked inhibition of Nox4/p53/Bax signaling.

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