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目的探讨缬沙坦对高糖诱导肾小球足细胞活化T细胞核因子2(NFAT2)活化及细胞凋亡的影响。方法将分化成熟的足细胞分组给予不同糖浓度、不同干预时间、NFAT2抑制剂11R-VIVIT、NFAT2活化剂ionomycin等刺激,采用Western blot检测足细胞胞核中NFAT2的表达水平、流式细胞仪检测足细胞凋亡情况。结果高糖能刺激足细胞NFAT2活化入核,20 mmol.L-1葡萄糖作用2 h时NFAT2活化入核达到高峰;这与Ionomycin作用相似,两者刺激下的NFAT2的表达水平无显著差异(P>0.05)。缬沙坦、11R-VIVIT与高糖共同刺激下,足细胞核中NFAT2的表达水平低于单纯高糖刺激(P<0.01),而缬沙坦和11R-VIVIT作用无显著差异(P>0.05)。20 mmol.L-1葡萄糖作用48 h时,足细胞凋亡率为(21.47±6.24)%,高于5.3 mmol.L-1葡萄糖作用48 h[(12.27±1.31)%,P<0.05]。缬沙坦与高糖共同刺激下,足细胞凋亡率低于单纯高糖刺激(P<0.01),与11R-VIVIT和高糖共同刺激下的凋亡率无显著差异(P>0.05)。结论缬沙坦可能通过抑制高糖诱导的足细胞NFAT2的过度活化,从而降低高糖诱导的细胞凋亡。
Objective To investigate the effects of valsartan on activation of nuclear factor 2 (NFAT2) and apoptosis in activated glomerular podocyte induced by high glucose. Methods The mature podocytes were treated with different concentrations of glucose, different intervention time, NF-κB inhibitor 11R-VIVIT and NFAT2 activator ionomycin. Western blot was used to detect NFAT2 expression in podocytes. Flow cytometry Podocyte apoptosis. Results High glucose stimulated NFAT2 activation in podocyte. NFAT2 activation peaked at 2 h after 20 mmol·L-1 glucose treatment. Similar to Ionomycin, the expression of NFAT2 was not significantly different (P > 0.05). Valsartan and 11R-VIVIT combined with high glucose, NFAT2 expression in podocyte nucleus was lower than that in high glucose alone group (P <0.01), while there was no significant difference between valsartan and 11R-VIVIT group (P> 0.05) . The rate of podocyte apoptosis was (21.47 ± 6.24)% at 20 mmol·L-1 glucose for 48 h, higher than that of 5.3 mmol.L-1 glucose for 48 h [(12.27 ± 1.31)%, P <0.05]. Valsartan and high glucose stimulation, podocyte apoptosis rate was lower than simple high glucose stimulation (P <0.01), and 11R-VIVIT and high glucose co-stimulated apoptosis rate was not significantly different (P> 0.05). Conclusion Valsartan can inhibit high glucose-induced NFAT2 overexpression, thereby reducing high glucose-induced apoptosis.