Expression of Gsα in mice with cardiac hypertrophy and effects of cardiac-specific Gsα deletion on heart development in young mice

Ping YIN; Qi ZHAO; Yujun SHI; Li SU

doi:10.16016/j.1000-5404.202101167

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Expression of Gsα in mice with cardiac hypertrophy and effects of cardiac-specific Gsα deletion on heart development in young mice

Basic Medicine | 更新时间：2026-01-09

- Expression of Gsα in mice with cardiac hypertrophy and effects of cardiac-specific Gsα deletion on heart development in young mice
- Journal of Third Military Medical University Vol. 43, Issue 14, Pages: 1319-1325(2021)
- 作者机构：
  
  1.400014 重庆，重庆医科大学附属第二医院心血管内科
  2.610041 成都，四川大学华西医院病理研究室
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81974036)
- DOI：10.16016/j.1000-5404.202101167
  CLC： R363.21;R394.3;R542.2
- Received：20 January 2021，
  
  Revised：2021-03-23，
  
  Published：30 July 2021
- 稿件说明：
移动端阅览
Ping YIN, Qi ZHAO, Yujun SHI, et al. Expression of Gsα in mice with cardiac hypertrophy and effects of cardiac-specific Gsα deletion on heart development in young mice[J]. Journal of Third Military Medical University, 2021, 43(14): 1319-1325.
DOI：

Ping YIN, Qi ZHAO, Yujun SHI, et al. Expression of Gsα in mice with cardiac hypertrophy and effects of cardiac-specific Gsα deletion on heart development in young mice[J]. Journal of Third Military Medical University, 2021, 43(14): 1319-1325. DOI： 10.16016/j.1000-5404.202101167.

摘要

目的

通过主动脉缩窄术(transverse aortic constriction，TAC)建立压力超负荷诱导心肌肥厚的小鼠模型，检测肥厚心肌组织中Gsα表达变化，同时构建诱导性心肌特异性Gsα缺失小鼠，观察Gsα缺失对幼鼠心肌发育的影响。

方法

10只健康雄性C57BL/6小鼠，按随机数字表法分为手术组(TAC组，

=5)和假手术组(Sham组，

=5)，TAC组小鼠行主动脉弓缩窄术，Sham组小鼠仅穿线而不缩窄主动脉。术后4周，采用超声心动图检测小鼠左心功能，运用病理组织染色观察小鼠心肌结构变化，利用RT-qPCR及Western blot检测小鼠心肌组织中Gsα表达；采用Cre-Loxp系统，将Gsα

fl/fl

小鼠与Myh6-MerCreMer小鼠杂交获得诱导性Myh6-MerCreMer

+/-

/Gsα

fl/fl

(MCM/Gsα

fl/fl

)小鼠。哺乳期MCM/Gsα

fl/fl

小鼠予腹腔注射他莫昔芬(tamoxifen

TMX

20 mg/mL)，连续10 d，通过哺乳方式将TMX传递给幼鼠，构建诱导性心肌特异性Gsα缺失幼鼠。记录幼鼠体质量增长以及生存率，利用病理组织染色观察心肌的结构变化。

结果

术后4周，超声心电图结果显示TAC组小鼠较Sham组小鼠舒张末期左室后壁增厚(

0.01)、舒张末期室间隔增厚(

0.05)、舒张末期左室内径减小(

0.05)，提示心肌发生了代偿性肥厚；组织病理学检测提示TAC组小鼠心肌横截面积显著增大(

0.01)，血管周围纤维化明显增加(

0.01)；RT-qPCR以及Western blot结果提示Gsα mRNA及蛋白表达水平增加(

0.05)。与玉米油诱导对照组相比，TMX诱导Gsα缺失的幼鼠出现生长迟缓、体质量显著降低(

0.05)；组织学染色提示TMX诱导的幼鼠心脏大小明显减小。

结论

Gsα在压力超负荷诱导心肌肥厚心肌中的表达上调。Gsα敲除后幼鼠生长延迟、心脏发育受阻，提示Gsα可能参与心脏生理发育及后负荷增加所致代偿性心肌肥厚过程。

Abstract

Objective

To detect the expression profile of alpha-subunit of the stimulatory G protein (Gsα) in a mouse model of pressure overload-induced cardiac hypertrophy by transverse aortic constriction (TAC)

and investigate the effects of cardiac-specific Gsα deletion on the cardiac development in young mice.

Methods

Ten healthy adult male C57BL/6 mice were randomized equally into model group (TAC) and sham operation (Sham) group. The mice of the TAC group were inflicted with TAC to construct a mouse model of pressure overload induced myocardial hypertrophy. Four weeks after surgery

echocardiography was employed to assess the left cardiac function

histopathological staining was used to observe the myocardial structure

and RT-qPCR as well as Western blotting were performed to detect the expression of Gsα in the myocardial tissues of the mice. In addition

a Myh6-MerCreMer

+/-

/Gsα

fl/fl

(MCM/ Gsα

fl/fl

) mouse model was established by hybridization of Gsα

fl/fl

mice and Myh6-MerCreMer mice using Cre/Loxp system. Then lactating female MCM/Gsα

fl/fl

mice were intraperitoneally injected with tamoxifen (TMX

20 mg/mL) for 10 consecutive days from the delivery day

transferring TMX to the young mice through lactation to construct inductive cardiac-specific Gsα-deficient pups. The body weight and survival rate of the pups were subsequently recorded

and the myocardial structural changes were detected using histological staining.

Results

As compared with the Sham group

the mice in the TAC group showed significantly increased thickness of end-diastolic left ventricular posterior wall (LVPWd) (

0.01) and end-diastolic interventricular septum (IVSd) (

0.05)

while decreased end-diastolic left ventricular internal diameter (LVIDd) (

0.05)

suggesting the onset of compensatory cardiac hypertrophy. Histopathological analysis indicated greater cross-sectional area of myocardium and higher perivascular fibrosis progression rate (

0.01)

and the mRNA and protein levels of Gsα were significantly increased in the TAC group (

0.05). Compared to the control group

the TMX-induced Gsα-deficient pups showed significant growth retardation and reduction of body weight (

0.05)

as well as reduced overall heart size.

Conclusion

The expression of Gsα is up-regulated in cardiac hypertrophy induced by pressure overload. Postnatal cardiac Gsα deletion retards the growth of young mice and inhibits their heart development

indicating that Gsα may be involved in heart physiological development and process of compensatory cardiac hypertrophy.

关键词

Keywords

references

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