JAK2/STAT3信号通路在右美托咪定抗小鼠脑缺血/再灌注损伤中的作用  

Role of JAK2/STAT3 Pathway in the Protective Effects of Dexmedetomidine Against Cerebral Ischemia/Reperfusion Injury in Mice

作　　者：门运政 童旭辉 胡淼 王雪如 刘刚[2] 董淑英 Men Yunzheng;Tong Xuhui;Hu Miao(School of Pharmacy,Bengbu Medical College,Bengbu 233030,China)

机构地区：[1]蚌埠医学院药学院药理学教研室,蚌埠233030 [2]蚌埠医学院第一附属医院麻醉科,蚌埠233004

出　　处：《华中科技大学学报（医学版）》2020年第6期662-666,699,共6页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：国家自然科学基金资助项目(No.81402930);蚌埠医学院研究生科研创新计划资助项目(No.Byycx1959)。

摘　　要：目的探讨JAK2/STAT3信号通路在右美托咪定(dexmedetomidine,DEX)抗小鼠脑缺血/再灌注(ischemia/reperfusion,I/R)损伤中的作用。方法将ICR小鼠随机分为4组:假手术(sham)组、I/R组、I/R+DEX组、I/R+DEX+JAK2/STAT3抑制剂AG490(I/R+DEX+AG490)组。采用改良线栓法制备小鼠大脑中动脉栓塞(middle cerebral artery occlusion,MCAO)模型,缺血1 h,再灌注24 h;采用Longa五分法对小鼠进行神经行为学评分;TTC染色法检测小鼠脑梗死体积,并计算脑梗死体积百分比;TUNEL染色法检测小鼠大脑皮层组织细胞凋亡情况;免疫印迹法检测脑组织中p-STAT3、STAT3、Bax、Bcl-2蛋白的表达变化。结果与sham组相比,I/R组小鼠神经行为学评分、脑梗死体积百分比、TUNEL染色阳性率、p-STAT3/STAT3及Bax/Bcl-2比值均增加;与I/R组相比,I/R+DEX组小鼠神经行为学评分、脑梗死体积百分比、TUNEL染色阳性率、Bax/Bcl-2比值均明显降低,p-STAT3/STAT3明显增加;在使用DEX的基础上使用AG490抑制JAK2/STAT3信号通路后,与I/R+DEX组相比,小鼠神经行为学评分、脑梗死体积百分比、TUNEL染色阳性率、Bax/Bcl-2比值显著增加,p-STAT3/STAT3降低。结论右美托咪定抗脑缺血/再灌注损伤的作用可能与JAK2/STAT3信号通路介导的细胞凋亡有关。Objective To investigate the role of JAK2/STAT3 pathway in the protective effects of dexmedetomidine(DEX)against cerebral ischemia/reperfusion(I/R)injury in mice.Methods ICR mice were randomly divided into 4 groups:sham group,I/R group,I/R+DEX group and I/R+DEX+AG490(JAK2/STAT3 signaling pathway inhibitor)group.The model of cerebral ischemia/reperfusion mice was established by middle cerebral artery occlusion(MCAO)with ischemia for 1 h and reperfusion for 24 h.Longa’s scores were used to evaluate the neurobehavioral deficiency of mice.The volume of cerebral infarction of mice was detected by TTC staining.TUNEL staining was used to detect the apoptosis of cortical cells of mice.Western blotting was performed to detect the expression levels of p-STAT3,STAT3,Bax and Bcl-2 protein.Results Compared with sham group,neurobehavioral score,cerebral infarction volume percentage,positive rate of TUNEL staining,p-STAT3/STAT3 protein expression and the ratio of Bax/Bcl-2 of mice in I/R group were significantly increased.While compared with I/R group,neurobehavioral score,cerebral infarction volume percentage,positive rate of TUNEL staining and the ratio of Bax/Bcl-2 of mice in I/R+DEX group were significantly decreased,and the expression of p-STAT3/STAT3 protein was significantly increased.When JAK2/STAT3 was inhibited by DEX combined with AG490,neurobehavioral score,cerebral infarction volume percentage,positive rate of TUNEL staining and the ratio of Bax/Bcl-2 of mice were significantly increased,and the expression of p-STAT3/STAT3 protein was significantly decreased.Conclusion The protective effects of dexmedetomidine against cerebral ischemia/reperfusion injury by reducing cell apoptosis may be related to the activation of the JAK2/STAT3 signaling pathway.

关 键 词：右美托咪定 脑缺血/再灌注损伤 JAK2/STAT3信号通路 细胞凋亡 

分 类 号：R364.12[医药卫生—病理学]