摘要
目的探究神经调节素1β(NRG1β)/JNK信号通路在大鼠脑缺血再灌注损伤的作用机制。方法选取40只6周龄SPF级SD大鼠,随机分为4组,空白对照组、模型组、神经调节素1β组、JNK信号通路抑制剂组。空白对照组不建模,其他三组采用改良线栓法制作大鼠大脑中动脉闭塞(MCAO)模型。造模成功后神经调节素1β组按照2μg/kg的注射比例给大鼠注射NRG1β,JNK信号通路抑制剂组将抑制剂用10%DMSO溶解稀释,向大鼠血管内注入5μl浓度为4 mg/kg的JNK信号通路抑制剂-SP600125。模型组和空白组使用等量的生理盐水处理。采用HE将大鼠脑组织细胞染色,观察缺血脑组织病理改变;采用原位末端标记法(TUNEL)检测缺血后神经细胞凋亡情况;采用改良神经功能缺损评分评价大鼠神经行为功能;检测大鼠脑组织含水量;采用Western blot法检测脑组织JNK表达水平。结果HE染色结果显示,相比空白对照组,模型组大鼠脑细胞列紊乱、细胞固缩且被染色加深,坏死细胞较多;相比模型组,神经调节素1β组和JNK信号通路抑制剂组大鼠脑细胞显著改善。相比空白对照组,模型组大鼠脑细胞凋亡指数、神经功能缺损评分、大鼠脑组织含水量、p-JNK蛋白表达水平显著升高,且差异有统计学意义(P<0.01);大鼠脑组织JNK蛋白表达水平无显著变化(P>0.05);相比模型组,神经调节素1β组和NK信号通路抑制剂组大鼠细胞凋亡指数、神经功能缺损评分、大鼠脑组织含水量、p-JNK蛋白表达水平显著降低,且差异有统计学意义(P<0.01);大鼠脑组织JNK蛋白表达水平无显著变化(P>0.05)。结论经NRG1β可以通过抑制JNK信号通路,从而缓解大鼠脑缺血再灌注损伤。
Objective To investigate the mechanism of NRG1β(neuregulin 1β)/JNK signaling pathway in rats with cerebral ischemia-reperfusion injury.Methods A total of 40 6-week-old SPF SD rats were randomly divided into four groups,including control group(control),model group(model),neuromodulin 1βgroup(NRG1β)and JNK signaling pathway inhibitor group(JNK inhabitor).The blank control group was not modeled,and the other three groups were treated with a modified suture method to make a rat middle cerebral artery occlusion(MCAO)model.After successful modeling,the rats in the neuromodulin 1βgroup were injected with NRG1βat a dose of 2μg/kg.The JNK signaling pathway inhibitor group was diluted with 10%DMSO and injected into the blood vessels of rats to a concentration of 5μl.Mg/kg of JNK signaling pathway inhibitor-SP600125.The model group and the blank group were treated with an equal amount of physiological saline.Rats brain tissue cells were stained with HE to observe the pathological changes of ischemic brain tissues.The apoptosis of neurons after ischemia was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling(TUNEL).The neurobehavioral function of rats was evaluated by modified neurological deficit score.The water content of rat brain tissue was detected.The expression level of JNK in brain tissues was detected by Western blot.Results The results of HE staining showed that compared with blank control group,the brain cell line was disordered,and the cells were pyknotic and deepened by staining,and there were more necrotic cells in model group.Compared with model group,the brain cells in neuromodulin 1βgroup and JNK signaling pathway inhibitor group were significantly improved.Compared with blank control group,the brain cell apoptosis index,neurological deficit score,water content of brain tissue and p-JNK protein expression level in model group were significantly increased(P<0.01).There was no significant change in the expression level of JNK protein in rat brain tissue(P>0.05).Compared with
作者
梁勇
谢子莎
毛文
LIANG Yong;XIE Zi-sha;MAO Wen(Department of Neurology,3201 Hospital Affiliated to Medical College of Xi'an Jiaotong University,Hanzhong Shaanxi 723000,China.)
出处
《临床和实验医学杂志》
2019年第11期1137-1141,共5页
Journal of Clinical and Experimental Medicine
