抗纤灵方对5/6肾切除大鼠肾纤维化及ACE-AngⅡ-AT1R轴的影响

吉晶; 何立群

doi:10.13422/j.cnki.syfjx.20190122

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抗纤灵方对5/6肾切除大鼠肾纤维化及ACE-AngⅡ-AT1R轴的影响

抗纤灵方治疗肾纤维化疾病专题 | 更新时间：2021-02-09

- 抗纤灵方对5/6肾切除大鼠肾纤维化及ACE-AngⅡ-AT1R轴的影响
- Effect of Kangxianling Decoction on Renal Fibrosis and ACE-AngⅡ-AT1R Axis in 5/6 Nephrectomized Rats
- 中国实验方剂学杂志 2019年25卷第1期页码：57-62
- 作者机构：
  
  1.上海中医药大学，上海　 200123;
  2.上海中医药大学　附属曙光医院，上海　 200021
- 作者简介：
  
  吉晶，在读博士，从事中医药防治慢性肾脏疾病的研究，E-mail：jj664758895@qq.com
  何立群，主任医师，博士生导师，教授，从事中医药防治慢性肾脏疾病的研究，Tel: 021-53821650, E-mail: heliqun59@163.com
- 基金信息：
  
  国家自然科学基金青年基金项目(81403358);上海市名老中医学术经验研究工作室项目(SHGZS-2017027);上海中医药大学研究生“创新能力培养”专项科研项目(Y201804)
- DOI：10.13422/j.cnki.syfjx.20190122
  中图分类号： R2-0;R22;R285.5;R289
- 收稿日期：2018-07-24，
  
  网络出版日期：2018-10-19，
  
  纸质出版日期：2019-01-05
- 稿件说明：
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吉晶, 何立群. 抗纤灵方对5/6肾切除大鼠肾纤维化及ACE-AngⅡ-AT1R轴的影响[J]. 中国实验方剂学杂志, 2019,25(1):57-62.

Jing JI, Li-qun HE. Effect of Kangxianling Decoction on Renal Fibrosis and ACE-AngⅡ-AT1R Axis in 5/6 Nephrectomized Rats[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(1): 57-62.
吉晶, 何立群. 抗纤灵方对5/6肾切除大鼠肾纤维化及ACE-AngⅡ-AT1R轴的影响[J]. 中国实验方剂学杂志, 2019,25(1):57-62. DOI： 10.13422/j.cnki.syfjx.20190122.

Jing JI, Li-qun HE. Effect of Kangxianling Decoction on Renal Fibrosis and ACE-AngⅡ-AT1R Axis in 5/6 Nephrectomized Rats[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(1): 57-62. DOI： 10.13422/j.cnki.syfjx.20190122.

摘要

目的：

探讨抗纤灵方对SD大鼠肾纤维化及肾素血管紧张素转换酶-血管紧张素Ⅱ-血管紧张素Ⅱ 1型受体（ACE-AngⅡ-AT1R）轴的影响。

方法：

将50只SD大鼠随机分成正常组（

=10），假手术组（

=10），5/6肾切除肾纤维化手术组（

=30）。术后2周，将手术组大鼠随机分成模型组、抗纤灵组、氯沙坦钾组，各组10只。抗纤灵组给予抗纤灵方（21 g·kg

－1

），氯沙坦钾组给予氯沙坦钾（33.3 g·kg

－1

），其他组给予等体积的生理盐水，每天1次，持续16周。测定生化指标血肌酐、尿素氮及24 h尿蛋白；苏木素-伊红（HE）染色观察肾组织病理改变；马松（Masson）染色观察肾纤维化程度；免疫组化检测ACE1，AT1R表达；蛋白免疫印迹法（Western blot）测定ACE1，AngⅡ，AT1R蛋白表达水平。

结果：

与正常组和假手术组比较，模型组的血肌酐、尿素氮及24 h尿蛋白均显著增加 (

0.01)；与模型组比较，抗纤灵组及氯沙坦钾组血肌酐、尿素氮及24 h尿蛋白水平均明显降低，差异具有统计学意义 (

0.05，

0.01)。HE及Masson染色显示，与模型组相比较，抗纤灵组及氯沙坦钾组肾脏纤维化程度都减轻。Western blot显示抗纤灵组及氯沙坦钾组ACE1，AngⅡ，AT1R明显低于模型组，差异有统计学意义 (

0.01)；免疫组化结果显示，ACE1，AT1R水平显示出与Western blot一样的变化。

结论：

抗纤灵方可延缓5/6肾切除大鼠肾纤维化的进展，该机制与抑制ACE-AngⅡ-AT1R轴的激活密切相关。

Abstract

Objective:

To study the therapeutic effect of Kangxianling decoction on renal fibrosis induced by 5/6 nephrectomy

and angiotensin converting enzyme-angiotensin Ⅱ-angiotensin Ⅱ 1 receptor (ACE-AngⅡ-AT1R) axis.

Method:

Totally 50 SD rats were randomly divided into the following groups: control group (

=10)

sham-operation group (

=10)

5/6 nephrectomized renal fibrosis model group (

=30). After two weeks

the rats in operation group were divided into the model group

Kangxianling group

and losartan potassium group

=10 in each group. Rats in losartan potassium group were administered with losartan potassium by gastrogavage

and rats in Kangxianling group were administered with Kangxianling by gastrogavage. Equal volume of saline was administered to rats in the other groups. The rats were put to death after 16 weeks of consecutive medication

and serum creatinine(SCr)

blood urea nitrogen(BUN)

24 h urine protein(24 h-Pro) were measured in each group. Hematoxylin-eosin(HE) staining was used to observe the pathological changes of kidney tissues

and the degree of renal fibrosis was observed by Masson staining. The expressions of ACE1 and AT1R were detected by immunohistochemistry. The protein expression levels of ACE1

AngⅡ and AT1R were determined by Western blot.

Result:

Compared with control and sham-operation groups

SCr

BUN and 24 h-Pro in model group were significantly increased (

0.01). Compared with model group

SCr

BUN and 24 h-Pro levels in the Kangxianling group and the losartan potassium group were significantly lower

with statistically significant differences (

0.05

0.01). HE and Masson staining showed that the degree of renal fibrosis was reduced in Kangxianling group and losartan potassium group compared with model group. Western blot showed that ACE1

AngⅡ and AT1R in Kangxianling group

and the losartan potassium were significantly lower than the model group

with statistically significant differences (

0.01). Immunohistochemistry results showed that the levels of ACE1 and AT1R showed the same changes as Western blot.

Conclusion:

Kangxianling decoction can delay the progress of renal fibrosis in 5/6 nephrectomized rats

which is closely related to the inhibition of ACE-AngⅡ-AT1R axis activation .

关键词

Keywords

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