Abstract: Objective To investigate the effects of different doses of BPI-1095 on the area of infarction and Bcl-2 protein expression in middle cerebral artery occlusion (MCAO) rats, as well as to explore the protection effects of BPI-1095 on ischemic brain tissue after local cerebral ischemia and its mechanism.Methods Model rats of cerebral ischemia were randomly divided into six groups. Each rat has been given different dosage of medicine and was sacrificed 24 h after treatment. The brain was removed from the skull. Iimmunohistochemistry staining was used to identify Bcl-2 expression in ischemic brain tissue, and the brain tissue was stained by 2% triphenyl-tetrazolium chloride (TTC) to measure the percentage of infarct area.Results 1. The percentage of infarct area was significantly decreased in treated rats with high or moderate dosage compared with the control group (P <0.05); 2. The expression of Bcl-2 protein increased at the boundary and cortex zone of the infarct compared with contralateral hemisphere area.The percentage of positive cells was significantly increased in rats treated with high dosage compared with control or ASA-treated rats. 3. There were no significant differences among three groups of different dosages of BPI-1095.Conclusion BPI-1095 may has a protection effect on brain, especially with high (240 mg/kg) or moderate dosage (80 mg/kg). The mechanism is closely related with the increase of Bcl-2 protein expression.

Key words: Infarction; Middle cerebral artery; BPI-1095; Cerebral ischemia; Bcl-2; Apoptosis

摘要：

目的:观察不同剂量BPI-1095对大鼠脑缺血后梗死面积百分数和神经元Bcl-2蛋白表达的影响，探讨BPI-1095对大鼠局灶性脑缺血损伤的保护作用及可能机制。

方法:建立大鼠局灶性脑缺血模型，随机分成6组：（1）BPI-1095大剂量（240 mg/kg）组；（2）BPI-1095中剂量（80 mg/kg）组；（3）BPI-1095小剂量（27 mg/kg）组；（4）阿司匹林（80 mg/kg）组；（5）安慰剂组；（6）假手术组。于模型建立10min后灌胃给予不同剂量的药物，24 h后断头取脑，应用免疫组化方法观察各组Bcl-2蛋白表达，同时用氯化三苯四唑（TTC）染色，测定大鼠大脑半球梗死面积百分数。结果:（1）BPI-1095大、中剂量治疗组梗死面积百分数明显小于安慰剂组（P <0.05）；而中小剂量组与阿司匹林组间比较没有统计学差异。（2）各组脑组织缺血周边和皮层凋亡保护蛋白Bcl-2表达阳性细胞较非缺血侧明显增多（P <0.05），以大剂量组最为明显，其阳性细胞百分数与安慰剂组和阿司匹林组比较均有统计学差异（P <0.05）。（3）BPI-1095不同剂量组之间Bcl-2蛋白表达没有统计学差异，不具有剂量依赖性。结论:BPI-1095对局灶性脑缺血有神经保护作用，以大剂量治疗组及中剂量治疗组疗效显著。其作用机制与上调Bcl-2蛋白的表达有关。

关键词: 梗死; 大脑中动脉; BPI-1095; 脑缺血; Bcl-2; 细胞凋亡