雌激素减轻脑缺血-再灌注损伤的可能机制探讨

The neuroprotective mechanism of estrogen in brain ischemia-reperfusion

目的 :研究雌激素对脑缺血 再灌注损伤后细胞凋亡 (又称细胞程序性死亡 )的影响。 方法 :大鼠分三组 :对照组、双侧卵巢切除 (OVX)组和OVX加 17β E2 组 (2 0 0 μg/kg体重 ,皮下注射每周 1次 ,连续 4周 )。 4周后用线栓法建立右侧大脑中动脉闭塞 1h ,闭塞 2h再灌注 0、1、3、6、2 2和 70h模型。采用放免法测定血浆雌激素水平 ,免疫组化方法检测Bax表达 ,TUNEL法标记凋亡细胞。 结果 :外源性雌激素替代可以对抗OVX引起的Bax过度表达 ,减少凋亡细胞数目。 结论 :雌激素的神经保护作用可能涉及降低氧化应激。

Objectives:In the present study,we observed whether chronic estrogen depletion and repletion affects apoptosis induced by cerebral ischemia reperfusion,and explore the potential mechanisms. Methods:Adult female rats were randomly assigned to 3 groups(ie,control,ovariectomized,and estrogen replacement groups).In the last group,E 2 valerate(200 microgram/kg) was subcutaneousely injected once a week after the OVX.Four weeks later,all rats were subjected to MCAO,and then killed at various points of time.We examined expressions of Bax by using immunohistochemistry method,analyzed serum estrogen concentration by radioimmunoassay, and detected apoptosis by TUNEL,in all rats. Results:Serum estrogen level was (0.185±0.124)pg/ml in intact female rats,(0.138±0.065)pg/ml in OVX rats, and (0.404±0.156)pg/ml in E 2 treated OVX rats.OVX increased focal expression of Bax and number of apoptotic cell,but those changs were inhibited by estrogen replacement. Conclusions:It strongly suggests that estrogen,whether exogenous or endogenous,play an important role in inhibiting neuromal degeneration induced by ischemia.