Shen Shuai II Recipe attenuates apoptosis in 5/6th renal ablation/infarction rats by inhibiting p53 and mitochondrial pathway of apoptosis

Background Chronic kidney disease (CKD) has become a serious challenge to global public health. Apoptosis is closely related to the evolution of CKD. In China, it has been noted that Chinese herbal medicine may be suitable for the treatment of CKD. Shen Shuai II Recipe (SSR) is a classic formula for the treatment of CKD in the clinic and proves the renprotective effects. However, the underlying mechanism remains unclear. The main purpose of this study was to investigate whether SSR could reduce apoptosis in 5/6 renal ablation/infarction (A/I) hypoxia model by regulating p53 and mitochondrial pathway of apoptosis.Methods 28 days after the 5/6 (A/I) surgery, Sprague-Dawley rats were randomly divided into four groups: sham group, 5/6 (A/I) group, 5/6 (A/I) + SSR group and 5/6 (A/I) +Losartan group (5/6 (A/I) +LOR). After 56 days of treatment, we mainly assessed the translocation of apoptotic factors in mitochondrial apoptosis pathway, the degree of mitochondrial dysfunction and the nuclear and mitochondrial translocation of p53. Furthermore, we detected the interaction of p53 with anti-apoptotic Bcl-xL and Bcl-2 proteins.Results SSR significantly inhibited the mitochondrial accumulation of pro-apoptotic protein Bax and Puma and release of cytochrome c from mitochondria to cytosol in the 5/6 (A/I) model. In addition, SSR improved the mitochondrial function and inhibited the nuclear and mitochondrial translocation of p53. SSR suppressed the p53 transactivation and the interaction of p53 with Bcl-xL and Bcl-2.Conclusions These results suggested that SSR could exert anti-apoptotic effects in the 5/6 (A/I) hypoxia model by inhibiting p53 transcriptional dependent and independent pro-apoptotic functions and the mitochondrial pathway of apoptosis.