[Triptolide combined with irbesartan synergistically blocks podocyte injury in a type 2 diabetes rat model].
摘要
OBJECTIVE: To investigate the protective effect of combination of triptolide and irbesartan on the podocytes in a type 2 diabetic(T2DM) rat model, and evaluate its mechanism. METHODS: T2DM rats were induced by fed with high-sucrose-high-fat diet combined with a low dose of streptozocin. The rats were randomly divided into 5 groups: normal control group (NC, n = 10), diabetes group (DM, n = 11), triptolide treatment group (DT, n = 12), irbesartan treatment group (DI, n = 12) and triptolide combined with irbesartan treatment group (DTI, n = 13). Ultrastructure of podocytes was observed by electronic microscopy and urinary albumin (UAL) excretion by ELISA was determined after 8 weeks. The expression of nephrin and bone morphogenetic protein-7 (BMP-7), connective tissue growth factor (CTGF), transforming growth factor (TGF)β(1) mRNA and proteins were detected by immunohistochemistry, real-time PCR and Western blot. RESULTS: Increased UAL was significantly attenuated in all treatment groups. Compared to NC group, UAL in DM group was increased significantly (0.45 ± 0.09 vs 6.36 ± 0.87, P < 0.01), while decreased in triptolide or irbesartan alone treatment group (2.48 ± 0.37 and 2.68 ± 0.42, both P < 0.01). Compared with those in control groups, kidney expression of nephrin, BMP-7 mRNA and proteins were downregulated while CTGF, TGFβ(1) mRNA and proteins were significantly upregulated in T2DM rats. Triptolide or irbesartan each alone moderately ameliorated albuminuria and podocyte damage. However, their combined usage showed a dramatic therapeutic synergism, manifested by prevention of progressive albuminuria, restoration of the glomerular filtration barrier, reversal of the decline in slit diaphragm proteins, reduction expression of CTGF, TGFβ(1), and upregulation of BMP-7. CONCLUSION: Our findings show that triptolide can increase the efficacy of irbesartan, leading to a more effective prevention of kidney disease in T2DM rat model, which may through upregulation of BMP-