【摘要】：目的：研究高糖刺激對足細(xì)胞瞬時受體電位陽離子通道蛋白6(TRPC6)表達的影響,探討糖尿病腎病(DKD)發(fā)生發(fā)展的可能機制。 方法：以永生化小鼠足細(xì)胞(MPC5)作為研究對象,予高濃度葡萄糖(30mmol/L)處理該細(xì)胞,并設(shè)正常糖對照組(5.6mmol/L)和甘露醇(25mmol/L)滲透壓處理組為正常對照組,高糖+低劑量纈沙坦(10-6mol/L)和高糖+高劑量纈沙坦(10-5mol/L)為治療組,高糖+U73122(鈣離子通道阻滯劑)為藥物對照組,各組細(xì)胞干預(yù)時間為48h。采用熒光定量PCR和western-blot方法檢測各組腎小球足細(xì)胞TRPC6、活化T細(xì)胞核因子(NFAT2)、nephrin、血管緊張素Ⅱ(AngⅡ) mRNA和蛋白的表達,流式細(xì)胞術(shù)檢測各組足細(xì)胞的凋亡率。 結(jié)果：與正常對照組相比,高糖組足細(xì)胞TRPC6、NFAT2、AngⅡ蛋白及mRNA水平明顯升高(P0.05),nephrin mRNA及蛋白水平明顯降低(P0.05),足細(xì)胞凋亡率升高(P0.05)；與高糖組相比,高劑量及低劑量纈沙坦均能降低TRPC6、 NFAT2、AngⅡ的表達及足細(xì)胞凋亡率,且高劑量纈沙坦組效果更顯著(P0.05)；U73122組TRPC6及NFAT2表達較高糖組明顯下降(P0.05)；滲透壓對照組與正常糖組之間各因子差別無統(tǒng)計學(xué)意義(P0.05)。 結(jié)論：高糖通過AngⅡ-NFAT-TRPC6信號通路損傷足細(xì)胞,增加足細(xì)胞凋亡,參與DKD的發(fā)生及發(fā)展。為血管緊張素受體拮抗劑通過此通路保護足細(xì)胞,治療DKD的提供了一新的理論基礎(chǔ)。
[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，

本文編號：2367706