氯化镧对大鼠脑缺血细胞凋亡保护作用的研究

The Protective Effect of Lanthanum Chloride on Apoptosis During Cerebral Ischemia in Rats

目的 探讨氯化镧对大鼠脑缺血诱导的细胞凋亡是否具有保护作用。方法 雄性SD大鼠 30只随机分为3组 :( 1)假手术组 ;( 2 )缺血组 ;( 3)氯化镧组。每组各 10只。采用线栓法制备大鼠局灶性脑缺血再灌注模型。Tunel染色观察 3组脑皮质凋亡细胞数 ;二苯胺法测定脑皮质DNA裂解率。结果 Tunel染色显示假手术组仅有散在的 0～ 3个凋亡细胞 ,而缺血组及氯化镧组均可见大量的凋亡细胞 ,但氯化镧组细胞凋亡数 14 0± 13明显低于缺血组 170± 9,有显著性差异 (P <0 .0 1)。缺血组再灌注后缺血区脑皮质DNA裂解率 ( 33.4± 1.3) %明显高于假手术组 ( 2 2 .1± 1.5 ) %及氯化镧组 ( 2 8± 2 .4 ) % ,有显著性差异 (P <0 .0 1)。结论 氯化镧对缺血再灌注诱导的脑皮质细胞凋亡具有一定的抑制作用。

Objective To investigate the effect of lanthanum chloride on apoptosis during cerebral ischemia.Methods Thirty male Sprague Dawley rats(weight 250～270 g)were randomly divided into sham operated rats(in which a 15 mm long nylon monofilament was inserted into the internal carotid artery for two hours),Ischemia group,and lanthanum chloride treated group.Focal cerebral ischemia was induced in rats of Ischemia group and lanthanum chloride group by transient occlusion of the right middle cerebral artery(MCAO)using an intraluminal thread model.All animals underwent ischemia for 2 h,followed by 24 h of reperfusion.lanthanum chloride(5 mg/kg)was administrated intravenously at 2 hours after MCAO in the lanthanum chloride group.The brains were taken at 24 h after reperfusion.Diphenylamine reaction was used to observe the change of the DNA fragment rate of cerebral cortex in five rats of every group.The brains of the other five rats in every group were paraffined and sectioned within 3 microns thick coronal slices.The slices were stained with the TdT smediated dUTP biotin nick end labeling(TUNEL)technique and the adjacent sections were stained with hematoxylin and eosin for analysis of ischemic cell damage,Results The DNA fragment rate increased after ischemia and reperfusion(0.334± 0.013 versus 0.221±0.015, P <0.01).Compared with Ischemia group lanthanum chloride could decrease the DNA splitting rate(0.28±0.024 versus 0.334±0.013, P <0.01).0 to 3 apoptotic cells presented in each hemisphere of sham operated rats as well as in the contralateral hemisphere of ischemic rats.The number of apoptotic cells of cortex was statistically lower in the lanthanum chloride group versus Ischemia group(140±13vernus170±9, P <0.01).Conclusion This study indicates that lanthanum chloride could provide neuroprotection by preventing the apoptotic components of cell from death after transient focal cerebral ischemia and may be effective as neuroprotective drugs.