神经调节素对大鼠脑缺血再灌注损伤后炎症反应的抑制作用和机制研究

Research on Inhibition and Mechanisms of Neuregulin for Inflammatory Response to Cerebral Ischemic Injury in Rats

目的:研究神经调节素及基质金属蛋白酶-9对于小鼠大脑缺血再灌注损伤后炎症反应的抑制作用和机制。方法:选取100只成年雄性大鼠,随机分成对照和治疗组。采用线栓方法由颈内到颈外进行插线处理,造成大脑中动脉处于闭塞状态的再灌注动物模型。治疗组颈动脉进行注射少量NRG-1β干预性治疗,通过氯化三苯基四氮唑(TTC)检查脑梗塞范围,细胞凋亡采用原位脱氧核糖核苷酸末端转移酶介导缺口末端进行标记,采用免疫组织化学、免疫荧光双标记法及免疫印迹法观察脑组织基质金属蛋白酶-9(MMP-9)表达。结果:脑缺血再灌注损伤后,随时间延长及缺氧,对照组大鼠大脑皮质和纹状体区脑组织细胞凋亡,并且胶质细胞MMP-9蛋白表达逐渐增加。治疗组大鼠经注射NRG-1β干预性治疗后,缺血脑组织梗死范围及其细胞凋亡数量相对呈明显下降趋势,胶质细胞MMP-9表达呈降低趋势。结论:大鼠脑缺血再灌注损伤后体内NRG-1β抑制胶质细胞MMP-9的表达,控制缺血脑组织梗死的范围并抑制正常细胞的凋亡,发挥了重要的抗炎作用,可作为对于大脑缺血再灌注损伤的研究新靶点。

Objective： To study the inhibitory effect and mechanism of the nerve regulation element and matrix metalloproteinase- 9 on the inflammatory response in mice after brain ischemia reperfusion injury. Methods： According to the randomized principle, 100 adult male rats were randomly divided into the control group and the treatment group. The animal model was made by means of Line plug which was from the intemal jugular to the outside of the neck that was used to induce the brain artery reperfusion. Rats in the treatment group were given the carotid beta interventional therapy by injected with a small dose of NRG -1 ~, the cerebral infarction range was detected by TTC, the cell apoptosis was calculated by TUNEL. The brain tissue matrix metalloproteinase-9 （MMP-9） was observed by the immunohistochemistry and immunofluorescence double labeling method and western blot. Results： After cerebral ischemia reperfusion injury as well as the extension of time and lack of oxygen, the rats brain tissues which were in the areas of the brain cortex and striatum represented apoptosis and the expression of MMP-9 protein of colloid cells gradually increased in the control group. While in the treatment group, the ischemic cerebral infarction range and the apoptosis number relatively appeared downward trend and the expression of MMP-9 protein of colloid cells showed a trend of decrease after the interventional treatment by injection of NRG-1 beta. Conclusions： After the ischemia reperfusion injury in rats, the expressions of MMP-9 in colloid cells of the rats inhibited by NRG 1 [3 that could control the scope of ischemia cerebral infarction and inhibit apoptosis of normal cells, and it is important for the antiinflammatory that can be used for the research of new targets on brain ischemia reperfusion injury.