肝郁型动脉粥样硬化小鼠模型建立及与易损斑块的相关性研究  

Establishment of Atherosclerosis Mouse Model of Liver Depression Type and Its Correlation with Vulnerable Plaque

作　　者：黄曾艳 彭春丽 黄曼萍[1] 刘永源[1] 李春燕 梁东辉[1] HUANG Zeng-yan;PENG Chun-li;HUANG Man-ping;LIU Yong-yuan;LI Chun-yan;LIANG Dong-hui(ZhuJiang Hospital of Southern Medical University,Guangzhou 510280,China;The First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510515,China;Maoming People's Hospital,Guangdong Maoming 525000,China)

机构地区：[1]南方医科大学珠江医院,广州510280 [2]广州中医药大学第一附属医院,广州510405 [3]茂名市人民医院,广东茂名525000

出　　处：《中国中医基础医学杂志》2022年第1期68-73,共6页JOURNAL OF BASIC CHINESE MEDICINE

基　　金：国家自然科学基金资助项目(81774036)-SDF-1/CXCR4自噬轴介导的巨噬细胞焦亡在情志所伤加重AS斑块易损性的作用及其机制研究。

摘　　要：目的:探讨肝郁与动脉粥样硬化(atherosclerosis,AS)易损斑块形成的相关性。方法:8周龄雄性ApoE-/-小鼠30只,分为正常对照组、高脂组、肝郁组每组各10只,8周龄C57BL/6J小鼠10只作为空白对照组。对照组给予正常饮食,其余组给予高脂饮食,采用高脂饲养加慢性不可预知温和刺激(chronic unpredictable mild stress,CUMS)方法制作肝郁型动脉粥样硬化小鼠模型。采用高架十字迷宫、旷场实验、6 min强迫游泳实验评价肝郁模型小鼠行为学,各组干预12周后用苏木精-伊红、油红“O”染色观察主动脉病理损伤程度。检测小鼠外周血总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDL-C)和低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)、去甲肾上腺素(norepinephrine,NE)含量;外周血血浆中性粒细胞总数(neutrophils,NEUT)、超敏C反应蛋白(high sensitivity c-reactive protein,hs-CRP)含量,荧光定量PCR检测肝脏CRP mRNA水平。结果:行为学实验表明肝郁模型小鼠焦虑指标增高(P<0.001),自发活动和探索行为减少(P<0.001),绝望行为时间延长(P<0.001)。与空白对照组、正常对照组、高脂组比较,肝郁组小鼠主动脉AS程度加重,体质量、TC、TG、LDL-C含量升高(P<0.05),HDL-C含量降低(P<0.05),NE表达量增加(P<0.05),血浆NEUT、hs-CRP、肝脏CRP mRNA表达量升高(P<0.05),差异均有统计学意义。结论:肝郁型动脉粥样硬化小鼠存在更加严重的炎症和脂质代谢紊乱,进一步加速了AS易损斑块形成。Objective:To explore the correlation between liver depression and formation of vulnerable atherosclerotic plaque.Methods:Thirty 8-week-old male apolipoprotein E knockout(ApoE-/-)mice were equally divided into normal control group,high fat group,liver depression group.Ten 8-week-old C57BL/6/J mice were used as blank control group.Mice in control groups were given normal diet,and mice in other groups were given high-fat diet.High fat diet and chronic unpredictable mild stimulation(CUMS)were used to establish the atherosclerosis model of liver depression type in mice.After twelve weeks of intervention,Elevated plus maze,open field test and 6-minutes forced swimming test were used to evaluate the behavior of liver depression model mice.The pathological damages of aortas were observed by hematoxylin eosin(HE)and oil red"O"staining.Body weight,c-reactive protein(CRP)mRNA of liver,levels of plasma norepinephrine(NE),neutrophils(NEUT),high sensitivity c-reactive protein(hsCRP)and lipid metabolism indexes include total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C)in Apoe-/-mice were measured.Results:The behavioral experiment showed that the anxiety level increased(P<0.001),the spontaneous activity and exploratory behavior decreased(P<0.001),and time of desperate behavior prolonged(P<0.001)in liver depression model mice.The degree of aortic atherosclerosis in liver depression group was aggravated.Weight,NE,TC,TG and LDL-C levels were increased(P<0.05),HDL-C levels were decreased(P<0.05),expressions of NEUT and hsCRP in plasma and liver CRP mRNA were increased in liver depression group when compared with the blank control group,the normal group and the high fat group(P<0.05).Conclusion:There exist more serious inflammation and lipid metabolism disorders in atherosclerosis model mice of liver depression type,which further accelerate the formation of vulnerable atherosclerotic plaque.

关 键 词：肝郁证 动脉粥样硬化 易损斑块 慢性不可预知温和刺激 

分 类 号：R541.4[医药卫生—心血管疾病]