异丙酚调控miR-21改善脑缺血/再灌注小鼠学习记忆能力以及对MAPK信号通路的影响  

Propofol regulates miR-21 to improve the learning and memory ability of cerebral ischemia-reperfusion mice and its effect on MAPK signaling pathway

作　　者：王明程 刘丽丹[1] 马晨光[1] 周南 吴秀英[1] WANG Ming-cheng;LIU Li-dan;MA Chen-guang;ZHOU Nan;WU Xiu-ying(Department of Anesthesiology,Shengjing Hospital,China Medical University,Shenyang 110004;Department of Anesthesiology,General Hospital of the Northern Theater Command,Shenyang 110016,China)

机构地区：[1]中国医科大学附属盛京医院麻醉科,辽宁沈阳110004 [2]北部战区总医院麻醉科,辽宁沈阳110016

出　　处：《解剖科学进展》2021年第4期440-444,共5页Progress of Anatomical Sciences

基　　金：辽宁省自然基金(20180551091)。

摘　　要：目的探讨异丙酚对脑缺血/再灌注(Cerebral ischemia reperfusion, CIR)损伤小鼠学习记忆能力的影响及其可能的作用机制。方法将40只10周龄C57BL/6小鼠随机分为假手术组(Sham)、模型组(CIR)、异丙酚组(CIR+PRO)及异丙酚+miR-21抑制剂组(inhibitor),每组10只,建立脑缺血/再灌注损伤小鼠模型,异丙酚组小鼠在灌注前被给予2 mg/kg异丙酚,miR-21抑制剂组进行病毒液脑室注射(1010 pfu/只)后3天建立CIR模型并给予2 mg/kg异丙酚。评价各组小鼠神经功能障碍评分;Morris水迷宫检测各组小鼠的学习记忆能力;测定小鼠脑梗死体积;检测各组小鼠脑组织含水量;qPCR检测小鼠脑内miR-21的表达;Western blot检测小鼠脑内丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)相关蛋白p-JNK、JNK、p-ERK1/2、ERK1/2、p-P38及P38表达。结果与CIR组相比,PRO能改善CIR小鼠神经功能障碍,提高CIR小鼠学习与记忆能力,降低CIR小鼠脑梗死体积和脑含水量,上调CIR小鼠梗死组织中miR-21表达,并抑制CIR小鼠脑组织梗死处p-JNK、pERK1/2和p-P38蛋白表达(P<0.05),但是异丙酚的上述作用均被miR-21抑制剂所抑制。结论异丙酚可改善脑缺血/再灌注小鼠的学习与记忆能力,其作用机制可能与调控miR-21表达,从而抑制MAPK信号通路活性有关。Objective To investigate the effect of propofol on l earning and memory of mice with ischemia reperfusion(CIR) injury and its possible mechanism. Methods forty C57 BL/6 mice(10 weeks old) were randomly divided into sham operation group(Sham), model group(CIR), propofol group(PRO) and propofol+miR-21 inhibitor group(inhibitor), with 10 mice in each group. A mouse model of cerebral ischemia reperfusion injury was prepared. Mice in the phenol group were given 2 mg/kg propofol before perfusion, and those in miR-21 inhibitor group were injected intraventricular. After 3 days, CIR model was established and propofol 2 mg/kg was given. The neurological dysfunction score of each group of mice was evaluated;Morris water maze was uesd to detect the learning and memory ability of each group of mice;The volume of mouse cerebral infarction was measured;The water content of the brain tissue of each group of mice were measured;qPCR was used to detect the expression of miR-21 in brain;Western blot was used to detect the expression of MAPK pathway related proteins p-JNK, JNK, p-ERK1/2, ERK1/2, p-P38 and P38 in brain. Results Compared with the CIR group, PRO significantly improved the neurological dysfunction of CIR mice, improved the learning ability and memory ability of CIR mice, reduced the cerebral infarction volume and brain water content, increased MiR-21 expression in infarcted tissues, and inhibits the expression of p-JNK, p-ERK1/2 and p-P38 proteins in infarcted brain tissues of CIR mice(P<0.05). However, the above effects of propofol were all attenuated or inhibited by miR-21 inhibitors. Conclusion Propofol can improve the learning and memory ability of CIR mice and exert neuroprotective effects. Its mechanism may be related to the regulation of miR-21 expression, thereby inhibiting the activity of MAPK signaling pathway.

关 键 词：异丙酚 脑缺血/再灌注 学习记忆能力 MIR-21 MAPK信号通路 

分 类 号：R743.31[医药卫生—神经病学与精神病学]