卵巢切除与老龄两种动物模型在研究GPR30心肌保护机制中的比较

Comparison of two animal models establishing by ovariectomy and aging to study the myocardial protective mechanism of GPR30

目的通过比较卵巢切除(ovariectomized,OVX)及老龄(Old)两种模型的心血管相关指标,明确模拟雌激素缺乏的两种模型的相同点及不同点,为研究G蛋白偶联受体30(G protein-coupled receptor 30,GPR30)的心肌保护机制选取合适的动物模型提供依据。方法建立OVX和Old两种动物模型,通过超声心动图、ELISA、Western blot、形态学以及透射电镜等方法,比较各组的心功能、雌激素水平,心肌组织雌激素受体水平、心肌纤维化程度以及心肌组织线粒体变化。结果OVX组的心脏功能、雌激素水平及雌激素受体蛋白水平具有时间依赖性,OVX-8W的心脏功能显著低于正常对照组,雌激素水平及雌激素受体蛋白水平呈持续性下降;Old组的心脏功能显著低于正常对照组及OVX组,雌激素水平以及雌激素受体蛋白水平均显著低于正常对照组及OVX-4W组;Old模型组可见明显的心肌纤维化,心肌细胞显著变大,心体比显著增高,心肌细胞线粒体结构肿胀变形、嵴断裂,有空泡化。结论OVX及Old两种动物模型均可成功模拟雌激素水平降低。在与纤维化相关的心肌梗死、心力衰竭以及线粒体等能量代谢的相关研究中,建议选择Old动物模型;如果选择OVX模型,建议实验观察终点在OVX后4周以上;雌激素与血压、肥胖、缺血再灌等研究建议选择OVX模型。

Objective To clarify the similarities and differences between two models simulating estrogen deficiency by comparing cardiovascular indicators of Ovariectomized(OVX)and Old animals,and to provide evidence to study the myocardial protective mechanism of estrogen receptor G protein-coupled estrogen receptor 30(GPR30)in selected animal models.Methods OVX and Old animal models were established.Echocardiography,ELISA,Western blot,morphology,and transmission electron microscopy were used to compare the cardiac functions,estrogen level,estrogen receptor protein level in myocardial tissue,myocardial fibrosis,and mitochondrial changes in myocardial tissue.Results The cardiac functions,estrogen level,and estrogen receptor protein level in the OVX group were dependent on time.Cardiac functions in the OVX-8W group were significantly lower than those in the control group,and the estrogen and estrogen receptor protein levels were decreased continuously.Cardiac functions in the Old model group were significantly lower than those in control and OVX groups,and the levels of estrogen and estrogen receptor protein were significantly lower than those in control and OVX-4W groups.In the Old model group,obvious myocardial fibrosis was observed,and myocardial cells were significantly enlarged.The heart-to-body ratio was significantly increased,and the mitochondrial structure in myocardial cells was swollen and deformed.Mitochondrial cristae were broken,and vacuolation was observed.Conclusions Both OVX and Old animal models successfully simulate the decrease in the estrogen level.To study fibrosis related to myocardial infarction and heart failure,and conduct research related to mitochondria and other energy metabolism,it is recommended to choose the Old animal model.If the OVX model is selected,it is recommended that the experimental observation endpoint is more than 4 weeks after OVX.Studies on estrogen,blood pressure,obesity,ischemia and reperfusion should use the OVX model.