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他克莫司对血管紧张素II诱导的足细胞损伤的影响。

Influence of tacrolimus on podocyte injury inducted by angiotensin II.

作者信息

Shengyou Yu, Li Yu, Zhihong Hao, Yuanyuan Ma

机构信息

Department of Pediatric, Guangzhou First People's Hospital, Guangzhou Medical University, China.

Department of Pediatric, Guangzhou First People's Hospital, Guangzhou Medical University, China

出版信息

J Renin Angiotensin Aldosterone Syst. 2015 Jun;16(2):260-6. doi: 10.1177/1470320314568520. Epub 2015 Feb 3.

Abstract

OBJECTIVE

This study investigated the protective effect of FK506 in podocytes and the correlation of TRPC6 with podocyte injury repair.

METHODS

MPC5 were cultured in vitro, parallel with the control group, an Ang II stimulation group, and an FK506 intervention group. The apoptosis rate with flow cytometry also detected TRPC6 mRNA and protein expression by RT-PCR and Western blot, and then observed the distribution of TRPC6 with indirect immunofluorescence labeling under confocal microscope.

RESULTS

The activities of podocytes significantly increased after FK506 intervention for 24 hours and 48 hours when compared with the Ang II stimulation group, and the apoptosis rate was markedly lower than that of the Ang II stimulation group, while in contrast to TRPC6 mRNA and protein expression.

CONCLUSION

FK506 can directly act on the podocytes to inhibit Ang II-induced damage on podocyte structures and reduce the apoptosis rate of podocytes, which may be related to stabilizing TRPC6 expression and distribution in podocytes by FK506, thus maintaining the structure and function integrity of the slit diaphragm and playing a role in protecting podocytes and antiproteinuria.

摘要

目的

本研究探讨FK506对足细胞的保护作用以及瞬时受体电位通道蛋白6(TRPC6)与足细胞损伤修复的相关性。

方法

体外培养MPC5细胞,分为对照组、血管紧张素II(Ang II)刺激组和FK506干预组。采用流式细胞术检测细胞凋亡率,运用逆转录-聚合酶链反应(RT-PCR)和蛋白质免疫印迹法(Western blot)检测TRPC6 mRNA和蛋白表达,然后在共聚焦显微镜下通过间接免疫荧光标记观察TRPC6的分布。

结果

与Ang II刺激组相比,FK506干预24小时和48小时后足细胞活性显著增加,凋亡率明显低于Ang II刺激组,而TRPC6 mRNA和蛋白表达情况则相反。

结论

FK506可直接作用于足细胞,抑制Ang II诱导的足细胞结构损伤,降低足细胞凋亡率,这可能与FK506稳定足细胞中TRPC6的表达和分布有关,从而维持裂孔隔膜的结构和功能完整性,发挥保护足细胞和抗蛋白尿的作用。

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