Apelin-13侧脑室注射对大鼠脑缺血再灌注损伤的影响及机制研究

Effects and Underlying Mechanisms of Apelin-13 Injected by Intarcerebroventricular on Cerebral Ischemia-reperfusion Injury in Rat

目的研究Apelin-13侧脑室注射对大鼠脑缺血再灌注损伤的保护作用及相关机制。方法侧脑室埋管后,采用线栓法制备大鼠大脑中动脉栓塞模型,脑缺血2 h后侧脑室注射给药。再灌注24 h后进行Zea-Longa神经功能评分;TTC染色法测定大鼠脑梗死面积;试剂盒测定大鼠脑组织内诱导型一氧化氮合酶(inducible nitric oxide synthase,i NOS)和谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-PX)的活性;Western blot法测大鼠脑组织Bcl-2、Bax和Caspase-3三种蛋白的表达水平。结果 Apelin-13(1.0μg·kg-1)侧脑室给药能改善大脑的神经功能,减少脑缺血面积,降低i NOS活性,增加GSH-PX活性,增加Bcl-2的表达,减少Bax和Caspase-3的表达。结论Apelin-13对缺血再灌注脑组织保护的可能机制包括降低NO水平,加强自由基清除,以及调节凋亡相关蛋白表达。

Objective To investigate the effects and underlying mechanisms of Apelin-13 injected by intarcerebroventricular on cerebral ischemia-reperfusion injury in middle cerebral artery occlusive（ MCAO） rats.Method Focal cerebral ischemia in rats was established by 2 h occlusion of the middle cerebral artery and 24 h reperfusion. After 2h ischemia,Apelin-13 and NS were administrated intracerebroventricularly. The neurologic deficient scores were investigated according to Zea-Longa＇s Standard. The infarct areas were assessed with software Imagepro Plus 6. 0 after TTC staining. The activities of inducible nitric oxide synthase（ i NOS） and glutathione peroxidase（ GSH-PX） were determined by specific kit. And the levels of Bcl-2、Bax and Caspase-3 in central neutral system were measured by western blot. Result Apelin-13（1. 0 μg·kg^-1） could decrease the neurologic deficient score,reduce the infarct areas of the brain in CIRI rats,depressed the activity of i NOS,enhance the activity of GSH-PX,increase the expression of Bcl-2,and decrease the expression of Bax and Caspase-3. Conclusion Apelin-13 can protect the ischemia-reperfusion injury,the mechanism may be related to depressing the level of NO,getting rid of more ROS,adjusting the expression of apoptotic and anti-apoptotic proteins.