南方医科大学学报2018，Vol.38Issue(3)：296-304,9.DOI:10.3969/j.issn.1673-4254.2018.03.09
VEGF及TRPC6的表达与糖尿病肾病大鼠足细胞损伤的相关机制
Correlation between expressions of VEGF and TRPC6 and their roles in podocyte injury in rats with diabetic nephropathy
摘要
Abstract
Objective To analyze the correlation between the expressions of vascular endothelial growth factor (VEGF) and transient receptor potential canonical 6(TRPC6)and their role in podocyte injury in rats with diabetic nephropathy.Methods Forty SD rats with diabetic nephropathy induced by intraperitoneal injection of 65 mg/kg streptozotocin were randomized equally into 5 groups, including a diabetic nephropathy model group and 4 treatment groups, with 8 normal SD rats as the normal control group.In the 4 treatment groups,the rats received intraperitoneal injections with SU5416 at 5 mg/kg or 10 mg/kg twice a week or with LY294002 at 1 mg/kg or 2 mg/kg once daily for 8 weeks.Blood glucose,serum creatinine,blood urea nitrogen, and 24-h urinary protein levels of the rats were detected at different time points, and the pathologies in the renal tissue were observed using HE staining, PAS staining and immunohistochemistry. The expressions of VEGF, nephrin, and TRPC6 at mRNA and protein levels were detected using RT-PCR and Western blotting.Results Compared with normal control rats, the diabetic rats showed significantly increased fasting blood glucose, serum creatinine, blood urea nitrogen and 24-h urinary protein levels with decreased expressions of nephrin mRNA and protein(P<0.05)and increased expressions of VEGF and TRPC6 (P<0.05). Compared with the untreated diabetic rats, the rats with SU5416 treatment showed increased 24-h urinary protein,urea nitrogen,and nephrin expression and decreased TRPC6 expression without significant changes in fasting blood glucose,serum creatinine,or VEGF expression.The rats treated with LY294002 showed decreased 24-h urinary protein and TRPC6 expression without significant changes in fasting blood glucose,serum creatinine,urea nitrogen,or expressions of nephrin and VEGF.Conclusion The regulatory effect of VEGF on TRPC6 can be blocked by inhibiting VEGFR-2 or blocking PI3K/Akt signaling pathway.关键词
糖尿病肾病/足细胞/血管内皮生长因子/瞬时受体电位阳离子通道蛋白6/磷脂酰肌醇3激酶Key words
diabetic nephropathy/podocytes/vascular endothelial growth factor/transient receptor potential canonical 6/PI3K/Akt引用本文复制引用
朱晓娜,王玉环,吴娟娟,董鹏,张敏..VEGF及TRPC6的表达与糖尿病肾病大鼠足细胞损伤的相关机制[J].南方医科大学学报,2018,38(3):296-304,9.基金项目
西安市科技计划医学攻关项目(NO.SF1316) （NO.SF1316）
