Effects of ghrelin on myocardial remodeling matrix metalloproteinases expression in post-myocardial infarction rats with diabetes mellitus

Wang Li; Li Guiqiong; Chen Qingwei; Ke Dazhi

您当前的位置：

首页 >

文章列表页 >

Effects of ghrelin on myocardial remodeling matrix metalloproteinases expression in post-myocardial infarction rats with diabetes mellitus

更新时间：2023-12-18

- Effects of ghrelin on myocardial remodeling matrix metalloproteinases expression in post-myocardial infarction rats with diabetes mellitus
- Journal of Chongqing Medical University Vol. 40, Issue 4, Pages: 493-500(2015)
- 作者机构：
  
  重庆医科大学附属第二医院老年心血管科
- 作者简介：
- 基金信息：
- DOI：
  CLC：
- Published：2015，
扫描看全文
Wang Li, Li Guiqiong, Chen Qingwei, et al. Effects of ghrelin on myocardial remodeling matrix metalloproteinases expression in post-myocardial infarction rats with diabetes mellitus. [J]. Journal of Chongqing Medical University 40(4):493-500(2015)
DOI：

Wang Li, Li Guiqiong, Chen Qingwei, et al. Effects of ghrelin on myocardial remodeling matrix metalloproteinases expression in post-myocardial infarction rats with diabetes mellitus. [J]. Journal of Chongqing Medical University 40(4):493-500(2015) DOI：

摘要

目的：探讨生长激素促分泌物受体（growth hormone secretagogue receptor，GHSR）的内源性配体 ghrelin对糖尿病大鼠心肌梗死后心室重塑基质金属蛋白酶（matrix metalloptoteinases，MMPs）表达的影响。方法：选取7~8周龄的SD大鼠随机分为4组：①单纯心肌梗死组；②糖尿病合并心肌梗死组；③糖尿病合并心肌梗死+ghrelin干预组；④糖尿病合并心肌梗死+ghrelin+GHSR1a特异性拮抗剂[D-Lys3]-GHRP-6干预组。建立链脲佐菌素糖尿病大鼠模型，12周后所有大鼠均结扎冠状动脉左前降支建立急性心肌梗死模型。 Ghrelin干预组大鼠腹腔注射 ghrelin[200 ?滋g/（kg·d）]，ghrelin+[D-Lys3]-GHRP-6干预组大鼠分别腹腔注射 ghrelin[200 ?滋g/（kg·d）]+[D-Lys3]-GHRP-6[50 ?滋g/（kg·d）]，其余2组分别腹腔注射等量生理盐水。4周后苦味酸天狼猩红染色检测其心肌纤维化情况，Masson染色检测心肌梗死面积，免疫组织化学和 Western blot分别检测左心室心肌组织基质金属蛋白酶2（matrix metalloptoteinase-2，MMP-2）、基质金属蛋白酶9（matrix metalloptoteinase-9，MMP-9）和金属蛋白酶组织抑制因子1（tissue inhibitor of metalloprotroteinase-1，TIMP-1）分布与表达变化。结果：与单纯心肌梗死组相比，糖尿病合并心肌梗死组心肌胶原容量分数（P=0.003）、心肌梗死面积明显增加（P=0.001），MMP-2（P=0.000）和MMP-9（P=0.000）明显增高，心肌间质纤维增生。Ghrelin腹腔注射干预后可明显降低糖尿病心肌梗死大鼠胶原容量分数（P=0.001）、心肌梗死面积（P=0.005），MMP-2（P=0.001）和MMP-9（P=0.001）表达减少，心肌间质纤维增生减轻。TIMP-1在合并糖尿病的组别中均明显升高（P=0.000），但3组间无统计学意义（P ＞0.05）。Ghrelin的上述效应均被 [D-Lys3]-GHRP-6阻滞。结论：Ghrelin可通过抑制糖尿病心梗大鼠心肌组织 MMP-2和 MMP-9的表达，从而抑制糖尿病心梗大鼠心肌间质纤维化、减少心肌梗死面积，抑制心肌细胞外基质重塑。

Abstract

Objective：To investigate the effects of ghrelin on myocardial remodeling matrix metalloproteinases expression in post-my－ocardial infarction diabetic rats. Methods：Adult male SD rats were divided into four groups：myocardiac infarction（ＭＩ），diabetes mellitus+myocardiac infarction（DM+MI），DM+MI+ghrelin，DM+MI+ghrelin+GHSR1a inhibitor[D-Lys3]-GHRP-6. Diabetes was in－duced by injection of streptozotocin（STZ，60 mg/kg）. After three months，left anterior descending artery（LAD） ligation was performed in all groups. DM+MI+ghrelin group received ghrelin，200 ?滋g/（kg·d）. DM+MI+ghrelin+[D-Lys3]-GHRP-6 group received ghrelin， 200 ?滋g/（kg·d） and [D-Lys3]-GHRP-6，50 mg/（kg·d）. The other two groups received the same amount sterile normal saline only. Four weeks later，Sirius red staining was used to detect myocardial fibrosis. Myocardial infarct size was detected by Masson staining. The distribution and expressions of matrix metalloptoteinase-2（MMP-2），matrix metalloptoteinase-9（MMP-9） and tissue inhibitor of metalloprotroteinase-1（TIMP-1） were detected by immunohis－tochemistry and Western blot，separately. Results：Myocardial collagen volume fraction（P=0.003），myocardial infarct size（P=0.001），the expression of MMP-2（P=0.000） and MMP-9（P=0.000） were significantly increased in DM+MI group than in MI group. After ghrelin administration，myocardial collagen volume fraction（P=0.001），myocardial infarct size（P=0.005），the expres－sion of MMP-2（P=0.001） and MMP-9（P=0.001） were significantly decreased in diabetic rats complicated with MI. TIMP-1 was sig－nificantly higher in diabetic groups than in MI group（P=0.000），without significant difference among these groups（P ＞0.05）. However，[D-Lys3]-GHRP-6 blocked the above effects of ghrelin. Conclusion：Ghrelin can inhibit myocardial extracellular matrix remodeling and reduce myocardial infarct size by suppressing the expressions of MMP-2 and MMP-9.

关键词

ghrelin生长激素促分泌物受体糖尿病心肌重塑基质金属蛋白酶

Keywords

ghrelingrowth hormone secretagogue receptordiabetesmyocardial remodelingmatrix metalloproteinase

references

Views

357

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Endothelial-overexpressed lipopolysaccharide-associated factor 1 promotes skin wound healing in diabetic mice by affecting the nuclear factor-kappa B signaling pathway

Human amniotic epithelial cells promote diabetic wound healing by inhibiting neutrophil extracellular traps

Analysis of the prevalence and influencing factors of diabetes in the natural population of Bai nationality in Dali

Risk factors of contrast-induced nephropathy in patients with diabetes after percutaneous coronary intervention and its prognosis

Ten-years variant prevalence of diabetes and pre-diabetes in a community of Chongqing

Related Author

Zhang Xing

Leng Weiling

Lei Xiaotian

He Yu

Liang Ziwen

Zhang Chunlin

Cheng Qingfeng

Zhang Yingxiao

Related Institution

Department of Endocrinology，The First Affiliated Hospital of Army Medical University

Department of Endocrinology,The Second Affiliated Hospital of Army Medical University

Department of Endocrinology,The First Affiliated Hospital of Chongqing Medical University

School of Public Health, Kunming Medical University

Baoshan College of Traditional Chinese Medicine

⁰