G-1通过抑制细胞凋亡减轻大鼠心肌缺血/再灌注损伤

目的 研究雌激素受体GPR30激动剂G-1对大鼠心肌缺血/再灌注损伤的保护作用.方法 32只雌性大鼠随机分为假手术组（Sham组）、卵巢切除组（OVX组）、缺血/再灌注组（I/R组）和G-1组,每组8只.除Sham组外,其他各组大鼠均切除双侧卵巢,G-1组卵巢切除后予G-1皮下注射2周,剂量为120 μg·kg-1·d-1.2周后取各组实验动物心脏,Langendorff灌流,记录左心室收缩压（LVSP）、左心室舒张末压（LVEDP）、左心室压变化最大速率（±dp/dtmax）;I/R组和G-1组进行离体心脏缺血/再灌注;检测各组心肌梗死面积,TUNEL检测心肌细胞凋亡.结果 与Sham组和OVX组相比,I/R组左心室发展压（LVDP）和±dp/dtmax降低,LVEDP升高,心肌梗死面积增加,凋亡心肌细胞数量增多;G-1组心功能改善,心肌梗死面积减小,心肌细胞凋亡数量减少.结论 G-1通过抑制细胞凋亡减轻大鼠心肌缺血/再灌注损伤.

G-1 alleviates myocardial ischemia/reperfusion injury in rats through inhibition of cardiomyocyte apoptosis

Objective To investigate the protective effects of the estrogen membrane receptor GPR30 agonist G - 1 on myocardial ischemia/reperfusion injury in rats. Methods A total of 32 female SD rats were randomly divided into four groups （ n = 8 each） ： a sham - operated control （Sham） group, an ovariectomized （OVX） group, an ischemia/ reperfusion （I/R） group and a G - 1 group. Bilateral ovariectomy was performed in all groups except the Sham group. A selective agonist of GPR30, G - 1 （ 120 μg·kg-1·d-1） was subcutaneously injected into the rats of the G - 1 group for 2 weeks. Two weeks later, the Langendorff assay was performed in each group to detect left ventricular systolic pressure （LVSP） , left ventricular end - diastolic pressure （LVEDP） and the maximal rate of left ventricular pressure rise （ ＋ dp/ dtmax ）. Ischemia/reperfusion in isolated heart was performed in the ]JR and G - 1 groups. Myocardial infarction size was measured. TUNEL was used to examine cardiomyocyte apoptosis. Results Compared with the Sham and OVX groups, the I/R group showed decreased levels of left ventricular developed pressure （LVDP） and ＋ dp/dtmx but an increased level of LVEDP, with an enlarged infarct size and an increased number of apoptotic cells. The rats in the G - 1 group showed improvement in cardiac function and reduction of myocardial infarct size and the number of apoptotic cardiomyo- cytes. Conclusion G - 1 can alleviate myocardial ischemia/reperfusion injury in rats through inhibition of cardiomyo- cyte apoptosis.