冠心舒通对脑缺血再灌注大鼠学习记忆能力及脑组织Bcl-2、Bax蛋白表达的影响

摘要

目的：观察冠心舒通对脑缺血再灌注（ I/R）大鼠学习记忆能力及脑组织Bcl-2、Bax蛋白表达的影响，以探究冠心舒通对I/R损伤脑组织的保护机制。方法：以健康Wistar大鼠为研究对象，随机分为假手术组、脑I/R模型组、冠心舒通高剂量（1 g/kg）组和低剂量（0.5 g/kg）组，每组各15只。采用大鼠左侧颈总动脉结扎方法建立I/R模型，造模前每组分别每日灌胃给予生理盐水、生理盐水、冠心舒通高剂量和冠心舒通低剂量，连续7d；术后每天上午灌胃给予生理盐水、生理盐水、冠心舒通高剂量和冠心舒通低剂量，3 d后水迷宫训练同时继续给药，连续7 d，第8天进行Morris水迷宫测试；测试结束后处死大鼠取血液及脑组织，采用ELISA检测大鼠血清中Bcl-2和Bax的蛋白变化水平，采用HE染色观察大鼠脑组织的病理改变；采用免疫组织化学法检测大鼠脑组织中Bcl-2和Bax蛋白变化水平。结果：与假手术组比较，冠心舒通高剂量组大鼠测试潜伏期略延长、经过平台次数和平台象限停留时间略减少、血清及脑组织中Bax蛋白水平略升高、Bcl-2蛋白水平略降低但无显著差异（ P＞0.05），冠心舒通低剂量组大鼠测试潜伏期延长、经过平台次数和平台象限停留时间减少、血清及脑组织中Bax蛋白水平升高、Bcl-2蛋白水平降低有显著差异（ P＜0.01），I/R模型组大鼠测试潜伏期明显延长、经过平台次数和平台象限停留时间明显减少、血清及脑组织中Bax 蛋白水平明显升高、Bcl-2蛋白水平明显降低有显著差异（ P＜0.01）。结论：冠心舒通能明显提高Wistar大鼠空间记忆能力，并能通过降低Bax蛋白水平和提高Bcl-2蛋白水平，抑制脑I/R损伤后的细胞凋亡，从而对I/R脑组织具有保护作用。%Objective:Guanxinshutong on cerebral ischemia reperfusion ( I/R) in rats learning and memory ability and brain Bcl-2,Bax protein expression to explore the protection mechanisms of Guanxinshutong on cerebral I /R injury in brain tissue.Methods:Healthy Wistar rats for the study were randomly divided into sham operation group ,I/R model group,high dose Guanxinshutong (1 g/kg) and low dose Guanxinshutong (0.5 g/kg) group,n=15.cerebral I/R model was estabhished by using the left commom cartid artery ligation method,modeling each group were fed daily before saline ,saline,Guanxinshutong (1 g/kg) and Guanxinshutong (0.5 g/kg), continuous 7 days;3 d after water maze training while continuing administration ,continuous 7 d,the eight day ,Morris water maze test;after the test,the rats were sacrificed blood and brain tissue ,serum by ELISA of Bcl-2 and Bax protein levels change;using HE staining of rat brain pathology;using immunohistochemistry assay in rat brain organization of Bcl-2 and Bax protein levels changes.Results:Compared with the sham group ,Guanxinshutong high-dose group test latency slightly longer timers after platform and platform quadrant dwell decreased slightly ,serum and brain tissue slightly elevated levels of Bax protein ,Bcl-2 protein levels decreased slightly but not significantly different ( P>0.05 ) ,low-dose group Guanxinshutong through latency test in rats ,after the number of platforms and platform quadrant dwell time decreased , serum and brain tissue elevated levels of Bax protein , Bcl-2 protein content decreased significantly different(P<0.01),cerebral I/R model group was significantly prolonged latency test ,after the number of platforms and platform quadrant dwell time significantly reduced serum and brain tissue was significantly increased Bax protein ,Bcl-2 protein content decreased with significant differences ( P<0.01 ).Conclusion: Guanxinshutong can significantly improve spatial memory , and by reducing Bax protein content and increased Bcl-2 protein,inhibition of cerebral I/R injury of apoptosis,and thus the brain tissue I/R has a protective effect.