Research of Baoshentongluo Formula on Podocyte Apoptosis and p53 Pathway in KK-Ay Mice and Podocytes Cultured with High Glucose
Objective:To investigate the effect of Baoshentongluo formula on podocyte apoptosis and p53 pathway in KK-Ay mice and podocytes cultured with high glucose.Methods:KK-Ay mice were fed with high-fat diet to establish a diabetic mod-el.After successful modeling,the mice were randomly divided into model group(10 mice)and kidney-protecting formula group(10 mice),and 10 C57BL/6J mice were set up as the control group;in vitro mouse glomerular foot cells(MPC5)were divided into nor-mal control group,high glucose group and kidney-protecting formula containing drug serum group according to different culture con-ditions.The 24 h urine protein quantification(24 h-UTP)levels of mice were measured and histopathological examination of kidney was performed.The viability of podocytes was measured by CCK-8 method,the expression of apoptosis-related proteins Bcl-2,Bax,cleaved-caspase3 and p53,p-p53 were detected by Western blot,and the apoptosis of podocytes in each group was observed by TUNEL staining.Results:Compared with the control group,the model group showed significantly increased 24 h-UTP(P<0.01),proliferated glomerular mesangial cells,increased the extracellular matrix,elevated the proportion of apoptotic cells and the expression of cleaved-caspase3 protein(P<0.05),reduced the expression of anti-apoptotic protein Bcl-2,increased the expres-sion of pro-apoptotic protein Bax and the phosphorylation level of p53(P<0.01).Baoshentongluo formula intervention significantly reduced the 24 h-UTP level in KK-Ay mice(P<0.01),improved renal pathological state,restored the proportion of glomerular apoptotic cells and the expression of cleaved-caspase3(P<0.05),decreased the expression of Bcl-2,recovered the expression of Bax and p-p53(P<0.05).In vitro study showed that high glucose group were significantly decreased the activity of podocytes(P<0.01),increased the proportion of podocyte apoptosis and the expression of cleaved-caspase3(P<0.05),decreased the ex-pression of Bcl-2,elevated the expression of Bax and p-p53(P<0.05);Baoshentongluo formula-medicated serum could restore podocyte activity(P<0.01),and inhibite the occurrence of apoptosis,as well as reduce the expression of p-p53 in high glucose-induced podocytes(P<0.05).Conclusion:Baoshentongluo formula can alleviate podocytes apoptosis in KK-Ay mice and high glu-cose-induced podocytes,restore the imbalance between pro-apoptosis and anti-apoptosis,and inhibit the activation of p53 path-way,which may be the potential mechanism of its podocyte protective effect.
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