大鼠脑缺血再灌注模型ICAM-1表达与白细胞浸润关系及亚低温干预治疗的研究

目的　研究大鼠局灶性脑缺血再灌注后不同时程脑组织中的细胞间粘附分子 1 (ICAM 1 )表达规律 ,及其与白细胞浸润的关系 ,并探讨亚低温的治疗作用。方法　采用大鼠大脑中动脉 (MCA)线拴闭塞 /再通法建立大鼠局灶性脑缺血 再灌注模型 ,常温组分别于脑缺血 3小时再灌注 2小时、8小时、2 4小时、48小时、72小时后断头取脑 ;假手术组及亚低温组于脑缺血 3小时再灌注 2 4小时断头取脑 ,行ICAM 1免疫组化及组织HE染色 ,测定ICAM 1表达阳性微血管数及白细胞计数。结果　⑴脑缺血再灌注后 2小时 ,脑缺血的坏死周边区的微血管内皮细胞表达ICAM 1出现增高趋势 ,并于 2 4小时达到高峰 ,各组之间及各组与假手术组间均有显著差异 (均P <0 0 5) ;⑵脑缺血再灌注 8小时出现白细胞浸润 ,且浸润高峰也在 2 4小时 (P <0 0 1 ) ;⑶ICAM 1的表达与白细胞浸润呈正相关 (r =0 .82 7,P <0 0 1 ) ;⑷缺血早期进行亚低温治疗能明显减轻缺血再灌注后ICAM 1的表达及减少白细胞浸润 (P <0 0 1 )。结论　脑缺血再灌注后ICAM 1可介导白细胞和内皮细胞的粘附 ,加速白细胞的浸润 ,提示ICAM 1是造成脑缺血损伤的重要因素之一 ;亚低温的干预治疗能明显减轻缺血再灌注后脑组织病理形态学的损害程度。

Study on the interference therapy of mild hypothermia and correlation between ICAM-1 expression and leukocyte infiltration on cerebral ischemia-reperfusion in rats

Objective To study the correlation between the expression of intercellular adhesion molecule 1(ICAM 1) and leukocyte infiltration, and explore the effects of mild hypothermia.Methods ICAM 1 positive expression and leukocyte infiltration in the ischemic regions were determined using immunohistochemitry and histological HE staining techniques at different reperfusion time(2 h,8 h,24 h,48 h and 72 h) after middle cerebral artery occlusion (MCAO) for 3h in rats, and mild hypothermia was given after MCAO followed by 24h reperfusion.Results (1)The expression of ICAM 1 raised obviously 2h after cerebral ischemia reperfusion, and peaked at 24h ( P <0 01);There was a remarkable difference between the various groups and the sham operative group( P < 0 05 ).(2)At 8h,there was a slight expression of leukocyte infiltration, but they also peaked at 24h ( P <0 01);(3)There was a positive correlation between the expression of ICAM 1 and leukocyte infiltration( r =0.827, P <0 01);(4)Mild hypothermia could reduced the expression of ICAM 1 and leukocyte infiltration ( P <0 01).Conclusion ICAM 1 may mediate leukocyte endothlial adhesion and progression of leukocyte infiltration after cerebral ischemia reperfusion.The study suggests ICAM 1 may play an important roles in ischemic cerebral damage .We also find that mild hypothermia could decrease the pathological feature of brain damage after cerebral ischemia reperfusion.