褪黑素在脑缺血动物模型中的保护作用及其机制  

Protective effects of melatonin and its mechanism in animal models of cerebral ischemia

作　　者：凌厉 李书鹏 张长宁 桂书彦 陈立波 LING Li;LI Shu-Peng;ZHANG Chang-Ning(Department of Endocrinology,Xiehe Shenzhen Hospital,Huazhong University of Science and Technology Shenzhen 518052,Guangdong,China)

机构地区：[1]华中科技大学协和深圳医院内分泌科,广东深圳518052 [2]北京大学深圳研究生院化学生物学与生物技术学院,广东深圳518055

出　　处：《吉林医学》2022年第4期871-876,共6页Jilin Medical Journal

基　　金：深圳市南山区科技计划项目[项目编号:2020079]。

摘　　要：目的:探究褪黑素通过氧化应激反应参与脑缺血损伤保护的作用机制。方法:选取SD大鼠分为假手术组、脑缺血组、褪黑素预处理组和褪黑素处理组,取脑组织切片和蛋白进行TTC染色、HE染色及Western印迹检测。检测大鼠脑梗死面积及神经元凋亡、氧化应激及炎性反应相关通路蛋白p38、JNK、Nrf2、HO-1等的表达。结果:褪黑素处理减少了脑缺血以后的梗死体积。脑缺血后p38、JNK、HO-1蛋白表达显著增高,褪黑素预处理能下调p38/JNK通路蛋白的表达;Nrf2、HO-1在脑缺血后显著增高,Trx在脑缺血后显著降低,而褪黑素处理能够提高Trx蛋白的表达,对Nrf2表达无影响。结论:补充内源性抗氧化神经激素褪黑素可以通过调节MAPK/p38/JNK通路减轻脑缺血的神经损伤效应,围绕该靶点进行深入探究对褪黑素及其在缺血性脑损伤中的临床应用具有重要意义。Objective To explore the specific mechanism of melatonin in cerebral ischemia injury protection through oxidative stress response.Method A number of SD rats were selected and divided into sham operation group,cerebral ischemia group,melatonin preconditioning group and melatonin treated cerebral ischemia group.TTC staining,H&E staining and Western Blot were performed on brain tissue sections and proteins.Cerebral infarct size,neuronal apoptosis,oxidative stress and the expression of inflammation-related pathway proteins p38,JNK,Nrf2 and HO-1 were detected in rats of different groups.Results Melatonin treatment reduced the infarct volume after cerebral ischemia.The protein expressions of p38,JNK and HO-1 were significantly increased after cerebral ischemia,and melatonin pretreatment could down-regulate the expression of p38/JNK pathway proteins.Trx was significantly decreased after cerebral ischemia,and melatonin treatment could increase the expression of this protein,thus playing a neuroprotective role.Conclusion Supplementation of endogenous antioxidant neurohormone melatonin can reduce the nerve injury effect of cerebral ischemia by regulating the MAPK/p38/JNK pathway.It is of great significance to further explore the target of melatonin and its clinical application in ischemic brain injury.

关 键 词：褪黑素 缺血性脑损伤 神经炎症 抗氧化剂 大脑中动脉阻塞 

分 类 号：R743.3[医药卫生—神经病学与精神病学] R-332[医药卫生—临床医学]