高血脂通过低密度脂蛋白胆固醇受体与p38-MAPK信号通路加重脑缺血  

Low density lipoprotein receptor and p38-MAPK signaling pathway in mechanism of cerebral ischemia with high blood lipid

作　　者：王蕾[1] 郝迪[1] 王宏[1] 王梓[1] 刘伟伟[1] 聂卫[1] 刘洪斌[1] 

机构地区：[1]天津市医药科学研究所心脑血管药物研发中心,天津市300020

出　　处：《中国动脉硬化杂志》2017年第3期224-229,共6页Chinese Journal of Arteriosclerosis

基　　金：国家自然科学基金青年基金项目(81202801);天津市卫生和计划生育委员会科技基金项目(2015KR04)

摘　　要：目的初步探索p38-丝裂原激活蛋白激酶(p-38MAPK)与低密度脂蛋白胆固醇受体(LDLR)在高血脂加重脑缺血的作用。方法将大鼠分为假手术组(正常饲料)、正常+大脑中动脉栓塞(MCAO)组(正常饲料)与高脂+MCAO组(高脂饲料),喂养30天,行大脑中动脉线栓法(MCAO)造成局灶性脑缺血。测定血脂水平,通过神经活动评分、缺血脑组织梗死重量、TUNEL细胞凋亡、Western Blot测定p-p38蛋白表达、免疫荧光对LDLR与p-p38双染等指标,观察高脂饲料对脑缺血程度的影响。结果高脂+MCAO组血清甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDLC)均显著高于正常+MCAO组(P<0.01)。高脂+MCAO组与正常+MCAO组比较,神经活动评分明显升高(P<0.01),且程度随时间加重(P<0.01),缺血脑组织重量明显增加(P<0.01);脑皮层细胞凋亡率明显增加(P<0.01),海马组织p-p38蛋白表达显著增加(P<0.01),位于海马组织CA1区;LDLR荧光染色明显增加,位于海马组织锥体细胞层。结论 LDLR与p-p38在高血脂加重脑缺血的作用位点不同,LDLR染色定位于海马组织锥体细胞层,p-p38定位在CA1区非锥体细胞层,提示高血脂加重脑缺血可能从LDLR受体和p38-MAPK信号通路途径(与巨噬细胞炎性环节有关)两个环节起作用。Ahn The relationship between p38 mitogen activated protein（p38-MAPK） and low density lipoprotein receptor （LDLR） in high blood lipid and cerebral ischemia is not clear. This study aims to explore the prob- lem. Methods SD rats were divided into normal diet group and high fat diet group feeding for 30 days and the middle cerebral artery occlusion （MCAO）was induced by the middle cerebral artery occlusion. Serum lipid levels were determined. Neural activity score, infarct weight of ischemic brain tissue and apoptosis, p-p38 expression, LDLR and p- p38 double staining index were determined to observe the effect of high fat diet on the extent of cerebral ischemia. Re- suits Serum TG, TC, LDL of fat diet group were significantly higher than normal diet group. Neural activity score, infarct weight of ischemic brain tissue and apoptosis, p-p38 expression, LDLR and p-p38 expression were significantly higher than normal diet group. Conclusion p-p38 was located in the CA1 region. This experiment from LDLR receptor pathway and p38 MAPK signal pathway （ and macrophage inflammatory link ） of two link annotation high blood lipids as risk factors of cerebral ischemiaessence, provides pharmacology reference for the treatment of hyperlipidemia induced by cerebral ischemia.

关 键 词：局灶性脑缺血 低密度脂蛋白胆固醇受体 p38-丝裂原激活蛋白激酶信号通路 

分 类 号：R363[医药卫生—病理学]