大鼠脑局灶性缺血再灌注后梗死体积变化与低分子肝素的保护效应

Protective effect of low molecular heparin on infarct volume after focal cerebral ischemia/reperfusion in rats

目的:观察低分子肝素对大鼠脑缺血再灌注后不同时间点脑梗死体积的影响。方法:实验于2005-03/2005-06在华北煤炭医学院动物实验中心完成。①选用雄性SD大鼠90只,体质量280～330g。应用随机数字表法将大鼠分为3组:假手术组、缺血再灌注组、低分子肝素组,每组30只。假手术组:只游离右侧颈总动脉、颈内动脉、颈外动脉。缺血再灌注组和低分子肝素组:均采用改良Longa法制作大鼠右侧大脑中动脉闭塞局灶性脑缺血再灌注模型。缺血2h后分别腹腔注射生理盐水1mL和皮下注射低分子肝素(200IU/kg)生理盐水稀释液1mL。2组均于缺血2.5h后开始再灌注3,6,12,24,48h,每个时间点取6只进行观察。②分别称重应用四氮唑红染色法染成白色的梗死组织与染成红色的正常组织,以梗死组织占全脑湿重的百分比表示脑梗死体积。③采用两样本均数的t检验对两组间数据进行分析。结果:大鼠90只均进入结果分析。缺血再灌注组大鼠脑缺血再灌注3,6,12,24,48h时脑梗死体积分别为(17.28±2.69)%,(22.66±2.16)%,(30.17±4.17)%,(38.83±4.54)%,(43.75±2.66)%,低分子肝素组分别为(12.54±1.35)%,(19.83±2.32)%,(23.83±3.19)%,(30.33±2.50)%,(36.25±2.54)%,假手术组均为0。随着缺血再灌注时间的延长,缺血再灌注组脑梗死体积逐渐增大,低分子肝素组梗死体积较缺血再灌注同一时间组明显缩小(t=-2.376,-2.191,-2.96,-4.019,-4.446,P<0.05)。结论:脑缺血再灌注损伤随再灌注时间延长而加重,低分子肝素能减少脑梗死体积,缩小梗死范围,对大鼠脑缺血再灌注损伤后具有保护作用。

AIM： To study the effect of low molecular weight heparin on the cerebral infarct volume after local cerebral ischemia/raperfusion in rats at different time point. METHODS： The experiment was performed at the Animal Experimental Center of North China Coal Medical College from March to June 2005. ①Totally 90 male SD rats, with the body mass of 280-330 g were selected and randomly assigned into 3 groups： sham operation group, ischemia/reperfusion group, low molecular weight heparin group with 30 in each group. Sham operation group only received common carotid artery, internal carotid artery, and external carotid artery of right side isolation. Middle cerebral artery occlusion and focal cerebral ischemia/raperfusion models were established with modified Longa method in the right side of rats in the ischemia/reperfusion group and low molecular weight heparin group. 2 hours after ischemia 1 mL saline was injected with intraperitoneal injection and 1 mL（200 IU/kg） low molecular heparin saline dilution was injected with subcutaneous injection. Six rats were observed at each time point for reperfusion at hours 3, 6, 12, 24 and 48 after ischemia for 2.5 hours in the two groups. ②Infarcted tissues stained white and normal tissues stained red with TTC stain were weighed, respectively. Cerebral infarct volume was expressed with the percentage of infarcted tissues to wet weight of the whole brain. ③All data in the two groups were analyzed with t test. RESULTS： Totally 90 rats were involved in the result analysis. The cerebral infarct volume was （17.28±2.69）%,（22.66± 2.16）%,（30.17±4.17）%,（38.83±4.54）%,（43.75±2.66）%, respectively in the ischemia/reperfusion group, and （12.54± 1.35）% ,（19.83±2.32）% ,（23.83±3.19）% ,（30.33±2.50）%,（36.25±2.54）% in the low molecular heparin group, and it was 0 in the sham operation group at hours 3, 6, 12, 24 and 48 after cerebral ischemia/reperfusion. With the prolongation of ischemia/reperfusion duration, the cerebral infarct volume became large gradually in the ischemia/reperfusion group, and the volume became small markedly in the low molecular heparin group as compared with the ischemia/reperfusion group at the same time point （t =-2.376,-2.191 ,-2.96,-4.019,-4.446,P 〈 0.05）. CONCLUSION： The cerebral ischemia/reperfusion injury becomes severe with the prolongation of reperfusion duration. Low molecular heparin can reduce cerebral infarct volume, contract infarct range, and and have the protective effects after cerebral ischemia/reperfusion injury in rats.