高糖通过AngII-NFAT-TRPC6信号通路诱导足细胞损伤

发布时间：2018-12-07 19:21

【摘要】：目的：研究高糖刺激对足细胞瞬时受体电位阳离子通道蛋白6(TRPC6)表达的影响,探讨糖尿病肾病(DKD)发生发展的可能机制。 方法：以永生化小鼠足细胞(MPC5)作为研究对象,予高浓度葡萄糖(30mmol/L)处理该细胞,并设正常糖对照组(5.6mmol/L)和甘露醇(25mmol/L)渗透压处理组为正常对照组,高糖+低剂量缬沙坦(10-6mol/L)和高糖+高剂量缬沙坦(10-5mol/L)为治疗组,高糖+U73122(钙离子通道阻滞剂)为药物对照组,各组细胞干预时间为48h。采用荧光定量PCR和western-blot方法检测各组肾小球足细胞TRPC6、活化T细胞核因子(NFAT2)、nephrin、血管紧张素Ⅱ(AngⅡ) mRNA和蛋白的表达,流式细胞术检测各组足细胞的凋亡率。 结果：与正常对照组相比,高糖组足细胞TRPC6、NFAT2、AngⅡ蛋白及mRNA水平明显升高(P0.05),nephrin mRNA及蛋白水平明显降低(P0.05),足细胞凋亡率升高(P0.05)；与高糖组相比,高剂量及低剂量缬沙坦均能降低TRPC6、 NFAT2、AngⅡ的表达及足细胞凋亡率,且高剂量缬沙坦组效果更显著(P0.05)；U73122组TRPC6及NFAT2表达较高糖组明显下降(P0.05)；渗透压对照组与正常糖组之间各因子差别无统计学意义(P0.05)。 结论：高糖通过AngⅡ-NFAT-TRPC6信号通路损伤足细胞,增加足细胞凋亡,参与DKD的发生及发展。为血管紧张素受体拮抗剂通过此通路保护足细胞,治疗DKD的提供了一新的理论基础。
[Abstract]:Aim: to investigate the effect of hyperglycemia on the expression of cationic channel protein 6 (TRPC6) in podocytes and to explore the possible mechanism of (DKD) development in diabetic nephropathy. Methods: immortalized mouse podocytes (MPC5) were treated with high concentration glucose (30mmol/L), and the normal glucose control group (5.6mmol/L) and mannitol (25mmol/L) osmotic pressure group were used as the normal control group. High glucose low dose valsartan (10-6mol/L) and high glucose high dose valsartan (10-5mol/L) were used as treatment group and high glucose U73122 (calcium channel blocker) as drug control group. The expression of NFAT2), nephrin, angiotensin 鈪，

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