Establishment of rat model of sarcopenia by ovariectomy and estrogen replacement therapy

Yubin HUANG; Li LING; Zheng'ai XIONG

doi:10.16016/j.2097-0927.202303072

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Establishment of rat model of sarcopenia by ovariectomy and estrogen replacement therapy

Basic Medicine | 更新时间：2026-01-09

- Establishment of rat model of sarcopenia by ovariectomy and estrogen replacement therapy
- Journal of Army Medical University Vol. 45, Issue 18, Pages: 1937-1946(2023)
- 作者机构：
  
  400010 重庆，重庆医科大学附属第二医院妇产科
- 作者简介：
- 基金信息：
- DOI：10.16016/j.2097-0927.202303072
  CLC： R589.305;R711.51;R977.12
- Received：14 March 2023，
  
  Revised：2023-05-30，
  
  Published：30 September 2023
- 稿件说明：
移动端阅览
Yubin HUANG, Li LING, Zheng'ai XIONG. Establishment of rat model of sarcopenia by ovariectomy and estrogen replacement therapy[J]. Journal of Army Medical University, 2023, 45(18): 1937-1946.
DOI：

Yubin HUANG, Li LING, Zheng'ai XIONG. Establishment of rat model of sarcopenia by ovariectomy and estrogen replacement therapy[J]. Journal of Army Medical University, 2023, 45(18): 1937-1946. DOI： 10.16016/j.2097-0927.202303072.

摘要

目的

建立SD大鼠绝经后肌肉衰减症模型，观察雌激素补充对肌肉衰减症的治疗作用。

方法

① 44只12周龄雌性SD大鼠(体质量220±20 g)按体质量分层随机抽样分为假手术(SHAM)组、去卵巢(ovariectomized

X)组，每组22只。OVX组行双侧卵巢切除术，SHAM组行假手术，监测体质量，电子抓力仪测量大鼠前肢抓力，12周后通过双能X射线分析仪(DXA)分析身体成分，通过相对瘦质量判定建模是否成功，而后每组各处死10只取腓肠肌，用腓肠肌质量/体质量得出肌肉衰减症指数(sarcopenia index

SI)，HE染色观察腓肠肌肌纤维横截面积，电镜下观察肌原纤维超微结构。②余下大鼠进一步分为假手术(SHAM)组、假手术+油剂注射(SHAM+O)组、去卵巢(OVX)组、去卵巢+雌激素补充(OVX+E

)组，每组6只，OVX+E

组每日予以17β-雌激素腹部皮下注射，SHAM+O组每日予以10% DMSO+90%芝麻油皮下注射，监测体质量、前肢抓力，干预8周后DXA分析体成分，ELISA法测量血清E

、FSH，HE染色观察腓肠肌肌纤维横截面积，电镜下观察肌原纤维超微结构，免疫荧光染色分析Bax、Bcl-2的表达。

结果

① 建模12周后，OVX组相对瘦质量显著降低(

0.001)，提示建模成功，体质量(

0.001)、体脂率显著升高(

0.001)，相对抓力(

0.001)、SI值、肌纤维横截面积显著降低(

0.01)，电镜下线粒体密度降低(

=0.012)。②经雌激素补充治疗后，OVX+E

组抓力、相对瘦质量、体质量、体脂率、肌纤维横截面积、电镜下线粒体密度均恢复到SHAM组水平；免疫荧光显示OVX组较SHAM与OVX+E

组Bcl-2/Bax显著降低(

0.01)。

结论

成功建立了大鼠绝经后肌肉衰减症模型，雌激素补充治疗能显著改善去卵巢大鼠的肌肉衰减，可能与雌激素抑制肌细胞凋亡有关。

Abstract

Objective

To establish a rat model of postmenopausal sarcopenia and explore the therapeutic effect of estrogen supplementary therapy on the disease.

Methods

① Forty-four 12-week-old female SD rats (220±20 g) were randomly divided into sham group and ovariectomized (OVX) group by stratified random sampling based on body weight

with 22 rats in each group. The rats of the OVX group were given bilateral ovariectomy

while those of the SHAM group underwent sham surgery. The body weight was monitored

and the grip strength of the forelimb was measured using an electronic grip strength meter. In 12 weeks after surgery

the body composition was analyzed by X-ray absorptiometry (DXA) to identify the model establishment by relative lean mass. Ten rats in each group were sacrificed to harvest the gastrocnemius

and then sarcopenia index (SI) was calculated as the ratio of gastrocnemius mass to body weight. HE staining and transmission ele

ctron microscopy were applied respectively to observe the cross-sectional area of the muscle fibers and the structure of myofibrils were determined. ② The remaining rats were further divided into SHAM group

SHAM+O group

OVX group and OVX+E

group

with 6 rats in each group. 17β-estradiol was injected subcutaneously in OVX+E

group

while control solvent (10% DMSO+90%sesame oil) was injected subcutaneously in SHAM+O group. The grip strength and body composition were measured and body composition was analyzed. ELISA was used to measure the serum levels of E

and FSH

HE staining was employed to observe the cross-sectional area of gastrocnemius muscle fibers

electron microscopy was conducted to observe the ultrastructure of myofibrils

and immunofluorescence staining was applied to analyze the expression of Bax and Bcl-2.

Results

① After 12 weeks of modeling

the rats in the OVX group had significant lower relative lean mass (

0.001)

indicating the successful establishment of sarcopenia model

and had obviously increased body weight (

0.001) and body fat rate (

0.001)

but decreased relative grip (

0.001)

SI value

average cross sectional area of the muscle fibers (

0.01)

and mitochondrial density (

=0.012). ② Estrogen supplementary therapy resulted in similar body weight

body fat rate

grip strength

relative lean mass

SI value

average cross sectional area of the muscle fibers

and mitochondrial density in the rats in OVX+E

group when compared with those of SHAM group. Immunofluorescence assay re vealed that OVX group had a notably lower Bcl-2/Bax ratio than the SHAM and OVX+E

groups (

0.01).

Conclusion

A rat model of postmenopausal sarcopenia is successfully established. Estrogen supplementary therapy can significantly improve the muscle mass loss in ovariectomized rats

which may be associated with estrogen inhibiting myocyte apoptosis.

关键词

Keywords

references

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