姜黄素对高胆固醇血症模型大鼠脑微循环障碍的改善作用及其机制  

Improvement effect of curcumin on cerebral microcirculation disorder in hypercholesterolemia model rats and its mechanism

作　　者：李红芳[1] 杨绍 曹莫寒 袁丽丽 李晓琎 史才兴 王茁桠 亚白柳 LI Hongfang;YANG Shao;CAO Mohan;YUAN Lili;LI Xiaojin;SHI Caixing;WANG Zhuoya;YA Bailiu(Department of Neurology,Affiliated Hospital,Jining Medical University,Jining 272029,China;School of Integrated Chinese and Western Medicine,Jining Medical University,Jining 272067,China;School of Basic Medical Sciences,Jining Medical University,Jining 272067,China;Department of Histology and Embryology,School of Basic Medical Sciences,Jining Medical University,Jining 272067,China;Department of Physiology,School of Basic Medical Sciences,Jining Medical University,Jining 272067,China)

机构地区：[1]济宁医学院附属医院神经内科,山东济宁272029 [2]济宁医学院中西医结合学院,山东济宁272067 [3]济宁医学院基础医学院,山东济宁272067 [4]济宁医学院基础医学院组织学与胚胎学教研室,山东济宁272067 [5]济宁医学院基础医学院生理学教研室,山东济宁272067

出　　处：《吉林大学学报（医学版）》2021年第1期53-58,共6页Journal of Jilin University：Medicine Edition

基　　金：国家自然科学基金项目(81703490);山东省科技厅自然科学基金项目(ZR2015HQ019);山东省卫健委中医药科技发展计划项目(2019-0489);济宁医学院大学生创新训练计划项目(cx2019053,cx2019063,cx2017031,cx2020023,cx2020071,S201910443013);济宁医学院教师科研扶持基金项目(JY2017KJ011,JY2017KJ016)。

摘　　要：目的:探讨姜黄素对高胆固醇饮食致高胆固醇血症模型大鼠脑微循环氧化应激和炎症状态的影响,阐明其作用机制。方法:30只SD大鼠随机分为对照组、模型组和姜黄素组,每组10只。对照组大鼠每日给予普通饲料,其余2组大鼠每日给予高胆固醇饲料,连续喂饲28 d。造模同时灌胃给药,姜黄素组大鼠给予姜黄素200 mg·kg^-1·d^-1,对照组和模型组大鼠给予等量1%羧甲基纤维素钠溶液,每日1次。连续给药28 d后,取大鼠血清,采用酶法检测各项血脂水平。提取大鼠脑微血管,采用黄嘌呤氧化酶法检测大鼠脑微血管组织中超氧化物歧化酶(SOD)活性,硫代巴比妥酸法测定丙二醛(MDA)水平,Western blotting法检测大鼠脑微血管内皮细胞中细胞间黏附因子1(ICAM-1)、血管间黏附因子1(VCAM-1)和E-选择素(E-selectin)蛋白表达水平。结果:与对照组比较,模型组大鼠血清中总胆固醇(TC)、甘油三酯(TG)和低密度脂蛋白胆固醇(LDL-C)水平明显升高(P<0.01),高密度脂蛋白胆固醇(HDL-C)明显降低(P<0.01),大鼠脑微血管组织中SOD活性明显降低(P<0.01)、MDA水平明显升高(P<0.05),大鼠脑微血管内皮细胞中ICAM-1、VCAM-1和E-selectin蛋白表达水平均明显升高(P<0.05或P<0.01);与模型组比较,姜黄素组大鼠血清中TC、TG和LDL-C水平明显降低(P<0.05),HDL-C水平明显升高(P<0.05),大鼠脑微血管组织中SOD活性明显升高(P<0.05)、MDA水平明显降低(P<0.05),大鼠脑微血管内皮细胞中ICAM-1、VCAM-1和E-selectin蛋白表达水平明显降低(P<0.05)。结论:姜黄素可以通过改善高胆固醇血症模型大鼠的血脂状况,增加脑微血管抗氧化酶能力,减低氧化应激损伤,减少脑微循环内皮细胞中黏附因子表达,进而改善脑微循环障碍。Objective:To study the effects of curcumin on the oxidative stress and inflammation status of cerebral microcirculation in the hypercholesterolemia model rats induced by high cholesterol diet,and to elucidate their mechanisms.Methods:Thirsty SD rats were randomly divided into control group,model group and curcumin group(n=10).The rats in control group were given ordinary diet and the rats in other two groups were given high cholesterol diet daily for 28 d.At the same time,the rats in curcumin group were given 200 mg·kg^-1·d^-1 curcumin by gavage,and the rats in control group and model group were given 1%sodium carboxymethylcellulose solution;once a day for 28 d.The sera of rats were taken and the levels of blood lipids were detected by enzyme method.The cerebral microvessels of rats were extracted;the activity of superoxide dismutase(SOD)in cerebral microvessel was detected by xanthine oxidase method;the level of malondialdehyde(MDA)was detected by thiobarbituric acid method;the expression levels of intercellular adhesion molecule-1(ICAM-1),vascular cell adhesion molecule-1(VCAM-1)and E-selectin proteins in the cerebral microvessel endothelial cells of the rats were detected by Western blotting method.Results:Compared with control group,the total cholesterol(TC),triglyceride(TG),and low density lipoprotein-cholesterol(LDL-C)in serum of the rats in model group were significantly increased(P<0.01),the high density lipoprotein-cholesterol(HDL-C)in serum was significantly decreased(P<0.01),the SOD activity in cerebral microvessel was significantly decreased(P<0.01),the level of MDA was significantly increased(P<0.05),and the expression levels of ICAM-1,VCAM-1 and E-selectin proteins in cerebral microvessel endothelial cells were significantly increased(P<0.05 or P<0.01).Compared with model group,the TC,TG,LDL-C in serum of the rats in curcumin group were significantly decreased(P<0.05),the HDL-C in serum was significantly increased(P<0.05),the SOD activity in cerebral microvessel was significantly increased(P<0.05)

关 键 词：姜黄素 高胆固醇血症 脑微循环 氧化应激 黏附因子 

分 类 号：R285.5[医药卫生—中药学] R743[医药卫生—中医学]