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目的探讨雌激素对脑缺血再灌注神经干细胞(neural stem cell,NSC)内源性激活的作用。方法将44只雄性大鼠随机分成假手术组、对照组和实验组。采用传统的线栓法制备大鼠大脑中动脉闭塞再灌注模型,实验组大鼠腹腔注射苯甲酸雌二醇,对照组腹腔注射生理盐水,通过免疫组织化学技术标记大鼠海马齿状回颗粒下层(subgranular zone,SGZ)、侧脑室室下层(subventricular zone,SVZ)以及梗死皮质周边区在缺血再灌注3、7、111、8 d的5-溴脱氧尿嘧啶核苷(bromodeoxyuridine,BrdU)阳性细胞,并采用HPIAS图像分析系统进行分析。结果正常成年大鼠脑组织SGZ和SVZ存在少量Brdu阳性细胞,对照组脑缺血再灌注3 d SGZ、SVZ和梗死皮质周边Brdu阳性细胞的数量开始增多,7 d达到高峰,11 d后开始减少,18 d进一步下降。实验组与对照组相比,在各个时间点均能显著提高BrdU阳性细胞的数量(P<0.01),而且增殖可以持续11 d。结论脑缺血再灌注可激活脑内NSC的增殖,雌激素可以促进脑缺血再灌注多个区域NSC的增殖。
Objective To investigate the effect of estrogen on endogenous activation of neural stem cells (NSC) after cerebral ischemia-reperfusion. Methods Forty-four male rats were randomly divided into sham operation group, control group and experimental group. The middle cerebral artery occlusion and reperfusion model was established by the traditional method of thread occlusion. The rats in the experimental group were intraperitoneally injected with estradiol benzoate, the control group were injected with saline, and the hippocampal dentate gyrus granule was marked by immunohistochemistry Subcranular zone (SGZ), subventricular zone (SVZ) and the peripheral area of infarct cortex were positive for bromodeoxyuridine (BrdU) at 3,7,111 and 8 d after ischemia / reperfusion Cells were analyzed by HPIAS image analysis system. Results There were a few Brdu positive cells in SGZ and SVZ of normal adult rats. In the control group, the numbers of Brdu positive cells in SGZ, SVZ and infarct cortex began to increase on the 3rd day after cerebral ischemia-reperfusion, reached the peak on the 7th day and decreased on the 11th day , 18 d further decline. Compared with the control group, the numbers of BrdU positive cells in the experimental group and the control group increased significantly (P <0.01) at all time points, and the proliferation could last for 11 days. Conclusion Cerebral ischemia-reperfusion can activate the proliferation of NSC in the brain. Estrogen can promote the proliferation of NSC in multiple regions of cerebral ischemia-reperfusion.