Effect of Fushengong Prescreption on Regulation-antagonism Effect of ACE-AngⅡ-AT1R Axis and ACE2-Ang(1-7)-MASR Axis of Rats with Chronic Renal Failure

Ke XU; Xue-kuan HUANG; Qing SHEN; Yang ZHANG; Hong-yu LUO; Jia-yu TIAN; Bo ZOU; Qin YANG; Ke-ming HOU

doi:10.13422/j.cnki.syfjx.20210544

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Effect of Fushengong Prescreption on Regulation-antagonism Effect of ACE-AngⅡ-AT1R Axis and ACE2-Ang(1-7)-MASR Axis of Rats with Chronic Renal Failure

Pharmacology | 更新时间：2021-02-09

- Effect of Fushengong Prescreption on Regulation-antagonism Effect of ACE-AngⅡ-AT1R Axis and ACE2-Ang(1-7)-MASR Axis of Rats with Chronic Renal Failure
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 27, Issue 5, Pages: 62-69(2021)
- 作者机构：
  
  重庆医科大学中医药学院，附属第一医院，重庆 400016
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20210544
  CLC： R2-0;R289;R256.5
- Published：05 March 2021，
  
  Published Online：15 January 2021，
  
  Received：19 August 2020，
- 稿件说明：
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徐珂,黄学宽,沈清等.复肾功方对慢性肾衰竭大鼠ACE-AngⅡ-AT1R及ACE2-Ang(1-7)-MASR轴“调控-拮抗”作用的影响[J].中国实验方剂学杂志,2021,27(05):62-69.

XU Ke,HUANG Xue-kuan,SHEN Qing,et al.Effect of Fushengong Prescreption on Regulation-antagonism Effect of ACE-AngⅡ-AT1R Axis and ACE2-Ang(1-7)-MASR Axis of Rats with Chronic Renal Failure[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(05):62-69.
徐珂,黄学宽,沈清等.复肾功方对慢性肾衰竭大鼠ACE-AngⅡ-AT1R及ACE2-Ang(1-7)-MASR轴“调控-拮抗”作用的影响[J].中国实验方剂学杂志,2021,27(05):62-69. DOI： 10.13422/j.cnki.syfjx.20210544.

XU Ke,HUANG Xue-kuan,SHEN Qing,et al.Effect of Fushengong Prescreption on Regulation-antagonism Effect of ACE-AngⅡ-AT1R Axis and ACE2-Ang(1-7)-MASR Axis of Rats with Chronic Renal Failure[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(05):62-69. DOI： 10.13422/j.cnki.syfjx.20210544.

摘要

目的

研究复肾功方对腺嘌呤诱导的慢性肾衰竭（CRF）大鼠血管紧张素转化酶-血管紧张素Ⅱ-血管紧张素Ⅱ1型受体（ACE-AngⅡ-AT1R）轴与血管紧张素转化酶2-血管紧张素（1-7）-Mas受体［ACE2-Ang（1-7）-MASR］轴的“调控-拮抗”作用，探讨其延缓CRF进展的作用机制。

方法

将65只雄性SD大鼠随机分为正常组10只、造模组55只，正常组常规饲养，造模组进行为期28 d的0.25 g·kg

-1

腺嘌呤混悬液灌胃。模型建立后，将存活造模大鼠随机分为模型组，贝那普利组（0.01 g·kg

-1

·d

-1

），复肾功方低、中、高剂量（4，8，16 g·kg

-1

·d

-1

）组，正常组和模型组以等体积生理盐水灌胃，持续28 d。实验结束后，测量各组大鼠尾静脉舒张压（SBP），收缩压（DBP），并收集24 h尿液以测定24 h尿蛋白（24 h U-pro）；测定血清中肌酐（SCr），尿素氮（BUN）含量；苏木素-伊红（HE）染色观察肾组织形态；马松（Masson）染色观察肾间质纤维化程度；酶联免疫吸附测定（ELISA）检测血清和肾组织匀浆中AngⅡ，Ang（1-7）及血清中胱抑素C（CysC）的含量；蛋白免疫印迹法（Western blot）检测肾组织中ACE，ACE2，AT1R，MASR蛋白表达水平；免疫组化标记肾组织中ACE，ACE2蛋白的表达。

结果

与正常组比较，模型组大鼠血清SCr，BUN，CysC明显上升（

0.05），血清与肾组织中的AngⅡ含量明显增加，Ang（1-7）含量明显减少（

0.05），肾组织中ACE，AT1R蛋白表达量明显升高（

0.05），ACE2，MASR蛋白表达量明显降低（

0.05）；与模型组、贝那普利组比较，经复肾功方干预治疗后，大鼠血清SCr，BUN，CysC含量明显下降（

0.05），血清与肾组织中的AngⅡ含量显著减少，Ang（1-7）含量明显增加（

0.05），肾组织中ACE，AT1R蛋白表达量显著降低，ACE2，MASR蛋白表达量明显升高（

0.05），其中复肾功方高剂量效果最佳，复肾功方高、中、低剂量的效果呈剂量相关性。

结论

复肾功方可改善腺嘌呤所致CRF大鼠肾功能和肾脏的病理学改变，其机制可能与通过抑制ACE-AngⅡ-AT1R轴，同时促进ACE2-Ang（1-7）-MASR轴来延缓CRF的进展有关。

Abstract

Objective

To study the effect of Fushengong prescreption on the regulation-antagonism effect of angiotensin converting enzyme-angiotensin Ⅱ-angiotensin Ⅱ 1 receptor （ACE-AngⅡ-AT1R） axis and angiotensin converting enzyme 2-angiotensin （1-7）-Mas receptor［ACE2-Ang（1-7）-MASR］ axis of rats with chronic renal failure（CRF）， and to explore its mechanism of delaying the development of CRF.

Method

The 65 male SD rats were randomly divided into normal group （

=10） and modeling group （

=55）. The normal group was routinely reared， while the modeling group were administered by gavage with 0.25 g·kg

-1

adenine suspension for 28 days. After the model was successfully established， the survival model rats were randomly divided into model group， benazepril group（0.01 g·kg

-1

·d

-1

）and low，medium and high dose of Fushengong prescreption groups （4，8，16 g·kg

-1

·d

-1

）. The normal group and model group were administered the same volume of normal saline by gavage， lasted for 28 days. After the experiment， systolic blood pressure （SBP） and diastolic blood pressure （DBP） of caudal artery were measured， and 24-hour urine was collected to determine 24-hour urine protein （24 h U-pro）. The content of serum creatinine（SCr） and blood urea nitrogen （BUN） in the serum were measured， the histological morphology was observed by hematoxylin eosin（HE）staining， and the degree of renal interstitial fibrosis was observed by Masson staining. Enzyme linked immunosorbent assay （ELISA） was used to determine the contents of AngⅡ， Ang （1-7） and Cystatin C （CysC） in serum and renal homogenate. The protein level of ACE， ACE2， AT1R and MASR were detected by Western blot. The expression of ACE and ACE2 protein in renal tissues were detected by immunohistochemistry.

Result

Compared with normal group， the expression levels of SCr， BUN and CysC in model group were significantly increased（

0.05）， the content of AngⅡ in serum and kidney tissues were significantly increased， the content of Ang （1-7） were significantly decreased（

0.05）， the expression of ACE and AT1R protein in renal tissues were significantly increased（

0.05）， and the expression of ACE2 and MASR protein were significantly decreased（

0.05）. Compared with model group and benazepril group， after the intervention with Fushengong prescreption， the serum SCr，BUN and CysC decreased（

0.05），the content of AngⅡ in serum and kidney tissues decreased significantly，Ang（1-7） increased significantly（

0.05）， the expression of ACE and AT1R protein in renal tissues decreased significantly（

0.05）， ACE2 and MASR protein increased significantly（

0.05）. The high-dose Fushengong prescreption has the best effect. The high， medium and low-dose effects of Fushengong prescreption were dose-dependent.

Conclusion

Fushengong prescreption improved renal function and pathological change of kidney in adenine-induced rats with chronic renal failure. The mechanism may be related to the inhibition of ACE-AngⅡ-AT1R axis and promotion of ACE2-Ang（1-7）-MASR axis ，which leads to the delaying of the progression of chronic renal failure.

关键词

复肾功方慢性肾衰竭血管紧张素转化酶（ACE）-血管紧张素Ⅱ（AngⅡ）-AngⅡ1型受体（AT1R）轴血管紧张素转化酶2（ACE2）-血管紧张素（1-7）［Ang（1-7）］-Mas受体（MASR）轴调控-拮抗作用

Keywords

Fushengong prescreptionchronic renal failureangiotensin converting enzyme（ACE）-angiotensin Ⅱ（AngⅡ）-angiotensin Ⅱ 1 receptor （AT1R） axisangiotensin converting enzyme 2（ACE2）-angiotensin （1-7）［Ang-（1-7）］-Mas receptor （MASR） axisregulation-antagonism effect

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