中国脑血管病杂志2018，Vol.15Issue(4)：187-192,6.DOI:10.3969/j.issn.1672-5921.2018.04.004
G蛋白偶联雌激素受体介导的缺血性卒中大鼠模型的神经保护作用和机制探讨
G protein-coupled estrogen receptor mediated neuroprotective effect and mechanism discussion in a rat model of ischemic stroke
摘要
Abstract
Objective To investigate G protein-coupled estrogen receptor(GPER)mediated neuroprotective effect and mechanism in an ischemic stroke model. Methods Bilateral ovariectomy (OVX)was used to establish a castrated model of adult SPF grade female SD rats. Enzyme-linked immunosorbent assay was used to detect serum estrogen level at 4 weeks after procedure.Middle cerebral artery occlusion(MCAO)was use to prepare a stroke model.The rats were randomly divided into sham operation(n=6),MCAO(n=7),MCAO+estrogen(MCAO+E2,n=8),MCAO+agonist(MCAO+G1,n=8)and MCAO +antagonist G15(MCAO +G15,n =7)groups. The neurological severity score (NSS),2,3,5-triphenyltetrazolium chloride(TTC)staining were used to measure the volume of cerebral infarction in order to assess the effects of different interventions.Western blot was used to detect the protein expression of hypoxia inducible factor-1α(HIF-1α),c-Jun N-terminal kinase(JNK),and Caspase-3 in the ischemic penumbra. Results (1)Estrogen level:after OVX,The level of serum estrogen in rats was significantly lower than that before castration(20 ± 9 ng/L vs. 73 ± 21 ng/L,P <0. 01).(2)NSS score:the NSS score of MCAO in each group was significant higher than that in the sham operation group (P<0.01);The NSS score of the MCAO+G1 group was significantly lower than that of the MCAO group and the MCAO+G15 group(6.0 ±1.8 vs.11.9 ±2.0 and 10.0 ±2.1).The difference was statistically significant (all P<0.05).(3)Cerebral infarct volume:there was significant difference in infarcted volume between the sham operation group and all other groups(all P<0.01);Compared with the MCAO group and the MCAO+G15 group,the infarct volume of the MCAO+E2 group and MCAO+G1 group was significantly reduced(19.8 ± 4.0%,14.0 ± 2.9%)vs.29.7 ± 5.8% and 27.6 ± 3.6%).The difference was statistically significant (all P<0.05).(4)Results of Western blot:the relative optical density values of HIF-1α,JNK,and Caspase-3 of the MCAO group were higher than those of the MCAO + G1 group(all P <0.01). Conclusions GPER mediates the neuroprotective effect of estrogen in the ischemic stroke model.This protective effect is associated with the regulation of the expression levels of HIF-1α,JNK,and Caspase-3.关键词
卒中/雌激素/缺血性卒中/G蛋白偶联雌激素受体/细胞凋亡Key words
Stroke/Estrogen/Ischemic stroke/G-protein coupled estrogen receptor/Apoptosis引用本文复制引用
柳威,陈晓青,孙磊,胡强,董朝霞,王博,张梦莹,舒细记..G蛋白偶联雌激素受体介导的缺血性卒中大鼠模型的神经保护作用和机制探讨[J].中国脑血管病杂志,2018,15(4):187-192,6.基金项目
国家自然科学基金(81100988) （81100988）
湖北省自然科学基金(2015CFB561) （2015CFB561）
