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

发布时间：2018-03-29 20:56

本文选题：局灶性脑缺血　切入点：低密度脂蛋白胆固醇受体　出处：《中国动脉硬化杂志》2017年03期

【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(P0.01)。高脂+MCAO组与正常+MCAO组比较,神经活动评分明显升高(P0.01),且程度随时间加重(P0.01),缺血脑组织重量明显增加(P0.01);脑皮层细胞凋亡率明显增加(P0.01),海马组织p-p38蛋白表达显著增加(P0.01),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。
[Abstract]:Objective to investigate the effects of p38 mitogen-activated protein kinase (p38 MAPK) and low density lipoprotein cholesterol receptor (LDLR) on hyperlipidemia and exacerbation of cerebral ischemia. Methods Rats were divided into sham operation group (normal diet group) and middle cerebral artery embolism group (MCAE). MCAO group (normal diet) and high fat MCAO group (high fat feed) were fed for 30 days. Focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO). The level of blood lipid was measured, and the expression of p-p38 protein was detected by Blot of Tunel cell apoptosis and the double staining of LDLR and p-p38 by immunofluorescence. Results the serum triglyceride, total cholesterol, low density lipoprotein cholesterol (LDL-C) in the high fat MCAO group were significantly higher than those in the normal MCAO group (P 0.01). The comparison between the high fat MCAO group and the normal MCAO group showed that the serum triglyceride triglyceride (TG), total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) in the high fat MCAO group were significantly higher than those in the normal MCAO group. The nerve activity score increased significantly with time, and the weight of ischemic brain tissue increased significantly, the apoptosis rate of cerebral cortex cells increased significantly, the expression of p-p38 protein in hippocampus increased significantly, and the fluorescence staining of p-p38 in CA1 region of hippocampus increased significantly. Conclusion LDLR and p-p38 are located in the pyramidal cell layer of hippocampal pyramidal cell layer and located in the non-pyramidal cell layer of CA1 area. These results suggest that hyperlipidemia may play an important role in exacerbating cerebral ischemia by LDLR receptor and p38-MAPK signaling pathway (related to macrophage inflammation).
【作者单位】：天津市医药科学研究所心脑血管药物研发中心;
【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)
【分类号】：R589.2;R743

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