摘要
目的研究局部亚低温对脑缺血后半胱天冬氨酸酶-3(caspase-3)、细胞凋亡诱导因子(AIF)和微管相关蛋白-2(MAP-2)表达的影响,并探讨亚低温脑保护的机制。方法采用改良的Longa法制备永久性大鼠大脑中动脉闭塞(MCAO)模型。低温组于缺血后立即给予贴敷式局部亚低温(33℃)治疗2 h。于缺血后2、6、12、24 h及3 d、1周和2周取脑,进行HE染色,并采用SABC法进行免疫组化染色,检测大鼠脑缺血区caspase-3、AIF和MAP-2的表达。结果脑缺血后2 h,脑梗死病灶周围区即出现caspase-3和AIF免疫阳性细胞,24 h达高峰,之后开始逐渐减低,但在2周时仍可见少量免疫阳性细胞。caspase-3在缺血中心区和周围区均有表达,而AIF主要表达于脑梗死周围区。与常温组相比,低温组caspase-3和AIF表达显著减低,而MAP-2显著增加。结论亚低温能抑制caspase-3和AIF表达,促进MAP-2表达,并可抑制caspase介导的细胞凋亡,亦可抑制不依赖于caspase的AIF介导的细胞凋亡。
Objective To investigate the effect of local mild hypothermia on the expressions of caspase-3, apoptosis-inducing factor （AIF） and microtubule-associated protein-2 （MAP-2） after focal cerebral ischemia in rats, and to disclose the possible mechanism of neuroprotection by mild hypothermia. Methods Permanent middle cerebral artery occlusion （MCAO） was induced in Wistar rats. Intraischemic local mild hypothermia was applied for 2 hours （33℃） in the hypothermia group. Normal body temperature was maintained （37℃） in the normothermia group. After survival periods of 2, 6, 12, 24 h, 3 d, 1 week and 2 weeks, the rats were anesthetized and the brains were sampled. Hematoxylin ＆ eosin staining was used to identify cerebral infarcts. Immunohistochemical analysis was used to detect the expressions of caspase-3, AIF and MAP-2, Results The immunoreactivity of caspase-3 and AIF was detectable after 2-hour ischemia in the penumbra region, and was significantly increased after 24 hours, then decreased gradually. There were a few immunoreactivity positive neurons after 2 weeks. Immunoreactivity positive neurons of caspase-3 were detected in both ischemic core and penumbra. AIF was mainly expressed in the nucleus in penumbra. Compared with normothermia group, the expressions of caspase-3 and AIF were significantly lower, and MAP-2 was significantly higher in hypothermia group. Conclusions Mild hypothermia decreases expressions of caspase-3 and AIF, and increases expression of MAP-2. Mild hypothermia may diminish apoptosis through inhibition of both caspase-dependent and caspaseindependent neuronal cell death pathways and promotpromote cell survival by upregulative expression of MAP-2.
出处
《中国神经免疫学和神经病学杂志》
CAS
2007年第1期23-27,共5页
Chinese Journal of Neuroimmunology and Neurology
基金
黑龙江省博士后基金资助项目(LBH-Z05165)
作者简介
张艳（1972-），女，黑龙江省人，博士，主治医师，主要从事脑血管病和神经系统变性病的基础与临床研究。通讯地址：哈尔滨医科大学第一临床医学院神经内科，哈尔滨150001。联系电话，（0451）53643849—5025。
