G蛋白抑制肽改善醋酸脱氧皮质酮-高盐诱导的小鼠心肌肥厚和纤维化

汤克成; 刘巧; 杨胜乾; 钟斌; 罗清曼; 李晓辉

doi:10.16016/j.2097-0927.202112283

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G蛋白抑制肽改善醋酸脱氧皮质酮-高盐诱导的小鼠心肌肥厚和纤维化

基础医学 | 更新时间：2026-01-09

- G蛋白抑制肽改善醋酸脱氧皮质酮-高盐诱导的小鼠心肌肥厚和纤维化
- GCIP attenuates DOCA/salt-induced cardiac hypertrophy and fibrosis in mice
- 陆军军医大学学报 2022年44卷第6期页码：533-540
- 作者机构：
  
  400038 重庆，陆军军医大学(第三军医大学)药学与检验医学系药物研究所
- 作者简介：
  
  [李晓辉，E-mail：lpsh008@aliyun.com LI Xiaohui, E-mail: lpsh008@aliyun.com
- 基金信息：
  
  国家自然科学基金面上项目(81773742)
- DOI：10.16016/j.2097-0927.202112283
  中图分类号： R542.2;R965;R977.4
- 收稿：2022-01-05，
  
  修回：2022-02-04，
  
  纸质出版：2022-03-30
- 稿件说明：
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汤克成, 刘巧, 杨胜乾, 等. G蛋白抑制肽改善醋酸脱氧皮质酮-高盐诱导的小鼠心肌肥厚和纤维化[J]. 陆军军医大学学报, 2022,44(6):533-540.

Kecheng TANG, Qiao LIU, Shengqian YANG, et al. GCIP attenuates DOCA/salt-induced cardiac hypertrophy and fibrosis in mice[J]. Journal of Army Medical University, 2022, 44(6): 533-540.
汤克成, 刘巧, 杨胜乾, 等. G蛋白抑制肽改善醋酸脱氧皮质酮-高盐诱导的小鼠心肌肥厚和纤维化[J]. 陆军军医大学学报, 2022,44(6):533-540. DOI： 10.16016/j.2097-0927.202112283.

Kecheng TANG, Qiao LIU, Shengqian YANG, et al. GCIP attenuates DOCA/salt-induced cardiac hypertrophy and fibrosis in mice[J]. Journal of Army Medical University, 2022, 44(6): 533-540. DOI： 10.16016/j.2097-0927.202112283.

摘要

目的

探讨G蛋白抑制肽(G alpha q-protein carboxyl terminus imitation polypeptide

GCIP)对醋酸脱氧皮质酮(deoxycorticosterone acetate

DOCA)-高盐诱导的心肌肥厚和纤维化的改善作用。

方法

将61只雄性C57BL/6小鼠行单侧肾切除手术后通过完全随机分组法分为5组：空白对照组(

=10)、DOCA-高盐处理组(

=14)、GCIP 0.1 mg/kg组(

=12)、GCIP 0.3 mg/kg组(

=12)及GCIP 1.0 mg/kg组(

=13)。除空白对照组外，其余每组喂养1%氯化钠水溶液以及每隔1 d皮下注射DOCA(100 mg/kg)制备心肌肥厚和纤维化模型，同时GCIP 0.1、0.3、1.0 mg/kg组每日2次皮下注射相应剂量的GCIP。给药期间监测小鼠存活率；每4天采用无创血压测量系统检测小鼠血压；小动物超声成像系统检测小鼠心脏功能；HE染色、麦胚凝集素(wheat germ agglutinin

WGA)染色评估小鼠心肌肥厚；天狼星红染色评估小鼠心肌纤维化；Western blot分析心脏组织α-SMA、p38及ERK1/2蛋白表达或蛋白磷酸化水平。

结果

与空白对照组相比，DOCA-高盐处理组小鼠生

存率降低43%，血压升高25.61%，左心收缩功能降低且心肌组织可见肥厚和纤维化(

0.05)。GCIP处理能提高小鼠生存率(35%)，降低血压(12.40%)，改善左心收缩功能以及心肌肥厚和纤维化(

0.05)。DOCA-高盐处理组小鼠心脏组织中α-SMA蛋白含量以及p38和ERK1/2磷酸化蛋白的含量明显升高(

0.05)，GCIP处理能抑制α-SMA的表达和p38、ERK1/2的磷酸化(

0.05)。

结论

GCIP能明显改善DOCA-高盐诱导的小鼠心肌肥厚和纤维化，其机制与抑制p38和ERK1/2的磷酸化有关。

Abstract

Objective

To determine the effects of improvement of G alpha q-protein carboxyl terminus imitation polypeptide (GCIP) on deoxycorticosterone acetate (DOCA)/salt-induced cardiac hypertrophy and fibrosis in mice.

Methods

After unilateral nephrectomy

61 male C57BL/6 mice were randomly divided into control group (

=10)

DOCA-salt group (

=14)

GCIP 0.1 mg/kg group (

=12)

GCIP 0.3 mg/kg group (

=12) and GCIP 1.0 mg/kg group (

=13). Except control group

the mice in other groups were given subcutaneous injection of deoxycorticosterone acetate (100 mg/kg) every 2 d and replacement of drinking water with 1% NaCl to prepare cardiac hypertrophy and fibrosis model. At the same time

the GCIP groups were given subcutaneous injection of GCIP at corresponding doses

twice a day. Their survival rate was observed every day. The blood pressure (BP) was measured by a tail-cuff blood pressure system every 4 days

and cardiac function was assessed by echocardiography. Hematoxylin-Eosin (HE) and wheat germ agglutinin (WGA) staining in heart tissue were used to evaluate cardiac hypertrophy. Sirius red staining in heart tissue was used to evaluate cardiac fibrosis. Moreover

Western blot analysis was used to detect the expression of α-SMA

p38 and ERK1/2.

Results

Compared with the control group

the DOCA-salt group had obviously decreased survival rate (43%)

increased BP level (25.61%)

decreased le

ft ventricular systolic function

and obvious hypertrophy and fibrosis in hear tissue (

0.05). GCIP treatment significantly increased survival rate (35%)

decreased BP (12.40%)

improved left ventricular systolic function and attenuated cardiac hypertrophy and fibrosis (

0.05). Furthermore

the expression of α-SMA and phosphorylation of p38 and ERK1/2 were increased in the heart tissue of the DOCA/salt-treated mice (

0.05)

while GCIP treatment reversed above phenomena (

0.05).

Conclusion

GCIP can effectively inhibit DOCA/salt-induced hypertensive cardiac hypertrophy and fibrosis

which is associated with its inhibition on phosphorylation of p38 and ERK1/2.

关键词

Keywords

references

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