The effects of different doses of estradiol (E2) on cerebral ischemia in an in vitro model of oxygen and glucose deprivation and reperfusion and in a rat model of middle carotid artery occlusion.
The effects of different doses of estradiol (E2) on cerebral ischemia in an in vitro model of oxygen and glucose deprivation and reperfusion and in a rat model of middle carotid artery occlusion.
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不同剂量雌二醇（E2）对体外缺氧、缺糖再灌注模型和颈中动脉闭塞大鼠模型脑缺血的影响
DOI：
10.1186/1471-2202-14-118
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发表时间：
2013-10-09
期刊：
影响因子：
2.4
通讯作者：
Xiong LZ
中科院分区：
文献类型：
--
作者：
Ma YL;Qin P;Li Y;Shen L;Wang SQ;Dong HL;Hou WG;Xiong LZ
本研究通过体外和体内实验，探讨不同剂量的雌二醇（E2）对脑缺血的保护作用。5-溴脱氧尿苷（Brdu）掺入和流式细胞术分析结果表明，生理剂量的E2促进细胞增殖，药理剂量的E2抑制细胞增殖。缺氧缺糖（OGD）4 h再灌注20 h后，3-（4，5-二甲基噻唑-2-基）2，5-二苯基溴化四唑（MTT）测定、乳酸脱氢酶（LDH）释放测定、流式细胞术分析和Western印迹分析显示生理剂量的E2增强细胞活力，减少细胞凋亡，降低促凋亡蛋白caspase-3的表达。相反，药理剂量的E2降低细胞活力和诱导细胞凋亡。在体内，成年卵巢切除（OVX）雌性大鼠接受连续皮下注射不同剂量的E2 4周。采用大脑中动脉闭塞（MCAO）技术诱导短暂性脑缺血2 h，然后再灌注22 h。Garcia试验、TTC染色结果显示，与去卵巢组相比，6 μg/kg和20 μg/kg E2组大鼠神经功能缺损评分增加，梗死体积缩小，caspase-3表达减少。而50 μg/kg E2替代治疗组神经功能缺损评分较对照组、6 up/kg或20 μg/kg E2替代组明显降低，梗死体积明显增加，caspase-3表达明显增加。而药理或超生理剂量的E2对脑缺血后神经元有损伤作用。
BackgroundBecause neuroprotective effects of estrogen remain controversial, we aimed to investigate the effect of different doses of estradiol (E2) on cerebral ischemia using bothin vivoandin vitroexperiments.ResultsPC12 cells were cultured at physiological (10 nM and 20 nM) or pharmacological (10 μM and 20 μM) dosages of E2 for 24 hours (h). The results of 5-bromodeoxyuridine (Brdu) incorporation and flow cytometric analysis showed that physiological doses of E2 enhanced cell proliferation and pharmacological doses of E2 inhibited cell proliferation. After the cells were exposed to oxygen and glucose deprivation (OGD) for 4 h and reperfusion for 20 h, the results of 3-(4, 5-dimethylthiazol-2-yl) 2, 5-diphenyl tetrazolium bromide (MTT) assay, lactate dehydrogenase (LDH) release assay, flow cytometric analysis and Western blot analysis showed that physiological doses of E2 enhanced cell viability, reduced cell apoptosis and decreased the expression of pro-apoptotic protein caspase-3. In contrast, pharmacological doses of E2 decreased cell viability and induced cell apoptosis.In vivo, adult ovariectomized (OVX) female rats received continuous subcutaneous injection of different doses of E2 for 4 weeks. Transient cerebral ischemia was induced for 2 h using the middle cerebral artery occlusion (MCAO) technique, followed by 22 h of reperfusion. The results of Garcia test, 2, 3, 5-triphenyltetrazolium chloride (TTC) staining showed that 6 μg/kg and 20 μg/kg E2 replacement induced an increase in neurological deficit scores, a decrease in the infarct volume and a reduction in the expression of caspase-3 when compared to animals in the OVX group without E2 treatment. However, 50 μg/kg E2 replacement treatment decreased neurological deficit scores, increased the infarct volume and the expression of caspase-3 when compared to animals in the control group and 6 up/kg or 20 μg/kg E2 replacement group.ConclusionWe conclude that physiological levels of E2 exhibit neuroprotective effects on cerebral ischemia; whereas, pharmacological or supraphysiological doses of E2 have damaging effects on neurons after cerebral ischemia.
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影响因子：
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