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5/6 肾切除大鼠残肾中时钟蛋白的昼夜节律变化和定位改变。

Altered diurnal variation and localization of clock proteins in the remnant kidney of 5/6 nephrectomy rats.

机构信息

Department of Nephrology, Wuhan Central Hospital, Wuhan Hubei 430014,

出版信息

Nephrology (Carlton). 2013 Aug;18(8):555-62. doi: 10.1111/nep.12111.

DOI:10.1111/nep.12111
PMID:23738784
Abstract

AIM

To investigate the localization and diurnal variation of clock proteins (BMAL1, PER2) and clock output protein (DBP) in the remnant kidney of 5/6 nephrectomy rats (STNx).

METHODS

Male wistar rats were randomly divided into sham STNx group (Control) and STNx group. Rats were synchronized 12 weeks to the light: dark cycle 12:12 with light on from 07.00 hours (Zeitgeber time ZT 0). Kidneys were collected to detect the localization and expression rhythm of clock proteins (BMAL1, PER2 and DBP) every 4 h throughout the day by immunohistochemistry and Western blotting.

RESULTS

Clock proteins showed diurnal rhythm in the kidney of the control. But diurnal rhythm of clock proteins changed in the STNx rats. Acrophase of BMAL1, DBP and PER2 advanced 4 h, respectively; mesor of clock proteins increased in the STNx rats. BMAL1 was located in endothelial cells of glomerulus and tubular interstitial vasculars, and it was also expressed in nucleus of tubular cells in cortex and medulla. PER2 was mainly expressed in proximal tubular cells at the juncture of cortex and medulla. DBP was widely expressed in the kidney. The localization of BMAL1 and PER2 were changed in remnant kidneys of the STNx group.

CONCLUSION

The localization and diurnal variation of BMAL1, DBP and PER2 are changed in remnant kidney of 5/6 nephrectomy rats and are involved in diurnal rhythm of renal function.

摘要

目的

研究 5/6 肾切除大鼠(STNx)残肾中时钟蛋白(BMAL1、PER2)和时钟输出蛋白(DBP)的定位和昼夜变化。

方法

雄性 Wistar 大鼠随机分为假手术 STNx 组(对照组)和 STNx 组。大鼠同步化 12 周至光暗周期 12:12,光照时间为 07:00(时间生物标志物 ZT 0)。通过免疫组织化学和 Western blot 技术,每天每隔 4 h 收集肾脏,检测时钟蛋白(BMAL1、PER2 和 DBP)的定位和表达节律。

结果

时钟蛋白在对照组肾脏中表现出昼夜节律。但在 STNx 大鼠中,时钟蛋白的昼夜节律发生了变化。BMAL1、DBP 和 PER2 的峰相位分别提前 4 h;STNx 大鼠的时钟蛋白中值增加。BMAL1 位于肾小球内皮细胞和肾小管间质血管中,也表达于皮质和髓质肾小管细胞核中。PER2 主要表达于皮质和髓质交界处的近端肾小管细胞。DBP 在肾脏中广泛表达。STNx 组残肾中 BMAL1 和 PER2 的定位发生了改变。

结论

5/6 肾切除大鼠残肾中 BMAL1、DBP 和 PER2 的定位和昼夜变化与肾功能的昼夜节律有关。

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