化合物IMM-H004对大鼠急性全脑缺血/再灌注损伤的保护作用

Neuroprotective effect of compound IMM-H004 against transient global brain ischemia/reperfusion in rats

目的评价化合物IMM-H004不同剂量(1.5、3、6 mg·kg-1)对大鼠急性全脑缺血/再灌注损伤的保护作用。方法使用四血管结扎法(4VO,20 min)制作大鼠急性全脑缺血/再灌注损伤模型,造模前3天开始尾静脉注射给药(每天1次),参照25分评分法对大鼠进行行为学评分,用尼氏染色方法考察化合物IMM-H004对大鼠海马CA1区、CA3区神经元病理损伤的影响,Western blot检测Bax、Bcl-2表达。结果化合物IMM-H004(1.5、3、6 mg·kg-1)对大鼠急性全脑缺血/再灌注损伤后的行为学有明显的改善作用。假手术组海马CA1区、CA3区神经细胞层次较多,排列紧密,细胞形态完整,核仁清晰,全脑缺血/再灌注明显导致神经元数目减少,细胞皱缩,细胞带分布不均,甚至出现脱失和带中断,而化合物IMM-H004给药组可明显改善神经元形态及数量,逆转缺血/再灌注损伤引起的Bax/Bcl-2比值的升高,并且具有一定剂量依赖性。结论化合物IMM-H004对大鼠急性全脑缺血/再灌注损伤具有保护作用,可作为一种潜在的神经保护剂进行开发。

Aim To evaluate the protective effect of compound IMM-H004 （ 1.5,3,6 mg · kg^-1 ） against transient global brain ischemia/reperfusion in rats. Methods Adult male Sprague-Dawley rats were sub- jected to transient global cerebral ischemia for 20 rain by four-vessel occlusion. Compound IMM-H004 （1.5, 3,6 mg· kg^-1） was administrated by tail vein injec- tion three days before surgery （once per day）. Behav- ior deficits were detected by a 25-point scale （Table 1 ） modified from the previous literature. Nissl staining was applied to assess the neuronal injury after ischemi- a/reperfusion,the protein levels of Bax, Bcl-2 and ^- actin were detected by western blot. Results Com- pound IMM-H004 significantly improved the behavioral deficits and alleviated neuronal loss in the hippocampus （CA1, CA3） at 72 h after global cerebral ischemia/reperfusion. In the sham group, the neurons in CA1 and CA3 regions of hippocampus were tightly packed with complete structure and the nucleolus was clear. Global cerebral ischemia/reperfusion significantly de- creased the number of neurons, the relict neurons were shrunk, unevenly distributed. Pretreated with com- pound IMM-H004 significantly protected the neurons both in number and morphology, and IMM-H004 de- creased the ratio of Bax/Bcl-2 in a dose-dependent manner. Conclusions Compound IMM-H004 exerts a neuroprotective effect against transient global cerebral ischemia/reperfusion injury in rats and improves be- havior deficits.