Translocator protein promotes renal angiotensin Ⅱ type 1 receptor expression and increases blood pressure in spontaneously hypertensive rats

Yue CAI; Hao LUO; Xiaoyu PENG

doi:10.16016/j.1000-5404.201807001

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Translocator protein promotes renal angiotensin Ⅱ type 1 receptor expression and increases blood pressure in spontaneously hypertensive rats

Basic Medicine | 更新时间：2026-01-09

- Translocator protein promotes renal angiotensin Ⅱ type 1 receptor expression and increases blood pressure in spontaneously hypertensive rats
- Journal of Third Military Medical University Vol. 40, Issue 24, Pages: 2222-2228(2018)
- 作者机构：
  
  1.400042 重庆，陆军军医大学(第三军医大学)第三附属医院野战外科研究所心血管内科，重庆市心血管病研究所
  2.400042 重庆，陆军军医大学(第三军医大学)第三附属医院野战外科研究所重症医学科
  3.735018 甘肃酒泉，95877部队医院内科
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81770425)
- DOI：10.16016/j.1000-5404.201807001
  CLC： R341; R363.21; R544.1
- Received：01 July 2018，
  
  Revised：2018-09-21，
  
  Published：30 December 2018
- 稿件说明：
移动端阅览
Yue CAI, Hao LUO, Xiaoyu PENG. Translocator protein promotes renal angiotensin Ⅱ type 1 receptor expression and increases blood pressure in spontaneously hypertensive rats[J]. Journal of Third Military Medical University, 2018, 40(24): 2222-2228.
DOI：

Yue CAI, Hao LUO, Xiaoyu PENG. Translocator protein promotes renal angiotensin Ⅱ type 1 receptor expression and increases blood pressure in spontaneously hypertensive rats[J]. Journal of Third Military Medical University, 2018, 40(24): 2222-2228. DOI： 10.16016/j.1000-5404.201807001.

摘要

目的

探讨线粒体转位蛋白TSPO(translocator protein，TSPO)对肾脏血管紧张素Ⅱ1型受体表达及功能的影响，为高血压的防治提供新的思路。

方法

14周龄雄性正常血压大鼠(Wistar-Kyoto，WKY；体质量250~280 g)4只、雄性原发性高血压大鼠(spontaneously hypertensive rats，SHR；体质量250~280 g)16只，检测WKY和SHR肾脏TSPO蛋白表达水平，TSPO肾脏分布及细胞内定位。12只SHR随机分成TSPO抑制组和对照组(

=6)，TSPO抑制组每日腹腔注射Ro5-4864(TSPO抑制剂) 0.5 mg/kg，对照组注射等量生理盐水。采用无创鼠尾测压仪测血压；代谢笼收集24 h尿量；肾上腺动脉灌注血管紧张素1型受体拮抗剂(坎地沙坦)并检测AT

R功能及肾脏AT

R蛋白表达水平。采用Ro5-4864浓度和时间梯度处理肾脏近曲小管上皮细胞(renal proximal tubule，RPT)，检测AT

R蛋白表达水平。

结果

TSPO定位于线粒体；与WKY比较，SHR肾脏皮质特别是近曲小管TSPO表达明显增加。TSPO抑制组24 h尿量[(21.7±4.5)

.(13.5±3.5)mL/kg

]

及尿钠排泄率[(1.5±0.3)

.(1.0±0.2)mmol/kg

]

均高于对照组(

＜0.05)。肾上腺动脉灌注坎地沙坦后，TSPO抑制组尿流速[(5.9±2.0)

.(13.3±2.5)μL/min

]

及尿钠排泄率[(0.6±0.2)

.(1.6±0.6)mmol/min

]

均明显低于对照组(

＜0.05)。TSPO抑制组肾脏AT

R蛋白的表达显著低于对照组(

＜0.05)。PRT细胞AT

R蛋白表达与Ro5-4864呈浓度及时间依赖性。

结论

TSPO可能通过促进肾脏AT

R表达及功能增强，引起水钠潴留而促进SHR血压升高。

Abstract

Objective

To investigate the role of mitochondrial translocator protein (TSPO) in regulating the expression and function of renal angiotensin Ⅱ type 1 receptor (AT1R) in hypertensive rats and provide evidence for devising new strategies for the prevention and treatment of hypertension.

Methods

Four male Wistar-Kyoto (WKY) rats (14 weeks old

weight 250-280 g)

and 4 age-matched male spontaneously hypertensive rats (SHR

weight 250-280 g) were examined for the expression

renal distribution and intracellular localization of TSPO. Another 12 SHR were randomly divided into TSPO inhibition group (

=6) and control group (

=6) for daily intraperitoneal injection of Ro5-4864 (a TSPO inhibitor) at 0.5 mg/kg and an equal volume of normal saline

respectively. Blood pressure of the rats was monitored with non-invasive tail cuff blood pressure equipment

and the volume of 24-h urine was collected using metabolic cages. The changes in the function and renal expression of AT1R were detected using Western blotting after adrenal artery infusion of candesartan

an AT1R antagonist. The changes in the expression of AT1R in response to treatments with temporal and concentration gradients of Ro5-4864 were also detected in the renal proximal tubule (RPT) cells using Western blotting.

Results

TSPO expression was located in the mitochondria. Compared with WKY rats

SHR exhibited significantly increased expression of TSPO in the renal cortex

especially in the proximal convoluted tubules (

0.05). Compared with the control SHR

the Ro5-4864-treated SHR had significantly increased 24-h urine volume (21.7±4.5

13.5±3.5 mL/kg) and urinary sodium excretion (1.5±0.3

1.0±0.2 mmol/kg) (

0.05).

In Ro5-4864-treated SHR

adrenal artery infusion of candesartan caused obvious reductions in urine flow rate (5.9±2.0

13.3±2.5 μL/min) and urinary sodium excretion rate (0.6±0.2

1.6±0.6 mmol/min) with also significantly decreased renal expression of AT1R as compared with the control SHR (

0.05). In PRT cells

Ro5-4864 treatment reduced the expression of AT1R protein in

concentration-and time-dependent manner.

Conclusion

TSPO enhances the renal expression and function of AT1R

which causes sodium and water retention and leads to increased blood pressure in SHR.

关键词

Keywords

references

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