姜黄素对ApoE^(-/-)小鼠动脉粥样硬化易损斑块的稳定作用及其机制  

Stabilization of curcumin on atherosclerotic vulnerable plaques in ApoE^(-/-) mice and its mechanism

作　　者：于悦卿[1] 苑可心[2] 李永辉[3] 王洁[1] 赵培[1,2,3] 路永刚 帖彦清[1] YU Yueqing;YUAN Kexin;LI Yonghui;WANG Jie;ZHAO Pei;LU Yonggang;TIE Yanqing(Department of Clinical Laboratory,Hebei General Hospital,Shijiazhuang 050051,China)

机构地区：[1]河北省人民医院检验科,石家庄050051 [2]河北省人民医院心内一科,石家庄050051 [3]河北省疾病预防控制中心

出　　处：《山东医药》2022年第27期15-18,共4页Shandong Medical Journal

基　　金：河北省中医药管理局课题计划(2017062)。

摘　　要：目的探讨姜黄素对ApoE^(-/-)小鼠动脉粥样硬化(AS)易损斑块的稳定作用及其机制。方法用1.25%胆固醇高脂饲料饲养ApoE^(-/-)小鼠,建立AS模型。将建模成功的AS小鼠随机分为实验组及对照组,实验组将姜黄素混悬液1 mL每天灌胃1次,连续4周;对照组以等量生理盐水1 mL每天灌胃1次,连续4周。两组各7只于第4周疗程结束后麻醉致死,留取主动脉根部,行Movat染色法测算两组小鼠主动脉根部易损斑块的面积;免疫组织化学(IHC)染色法检测两组小鼠病变组织内巨噬细胞(Mac)数量;原位细胞凋亡检测(TUNEL)法测算两组小鼠主动脉根部易损斑块内Mac的凋亡指数。Western blotting法检测两组小鼠病变组织内p-PERK、CHOP、Caspase-3、Caspase-9蛋白。结果与对照组比较,实验组小鼠主动脉根部AS斑块面积缩小,Mac数减少,Mac凋亡指数降低(P均<0.05)。与对照组比较,实验组小鼠主动脉根部组织中PERK、CHOP、Caspase-9、Caspase-3蛋白表达水平下降(P均<0.05)。结论姜黄素具有稳定ApoE^(-/-)小鼠AS易损斑块的作用,其作用机制是通过抑制与凋亡相关的ERS-PERK-CHOP通路而发挥作用的。Objective To investigate the effect of curcumin on the stability of atherosclerosis(AS)vulnerable plaque in ApoE^(-/-)mice and its mechanism.Methods Fourteen ApoE^(-/-)mice were fed with 1.25%high-fat cholesterol di‐et to establish the AS models.The successfully modeled AS mice were randomly divided into the experimental group(cur‐cumin was mixed with 1 mL suspension of 100 mg/kg,once a day,for 4 weeks)and the control group(treated with the same amount of normal saline for 4 weeks),with 7 mice in each.At the end of the fourth week of treatment,the mice were anesthetized to death and the aortic root was obtained.Part of the aortic root was placed in 10%formalin fixative solution for fixation,dehydration,paraffin embedding and pathological serial sections.Movat staining was used to observe the area of vulnerable plaques in the aortic root of mice in the two groups.The number of macrophages(Mac)in the diseased tis‐sues was detected by IHC staining in the two groups.In situ apoptosis assay(TUNEL)was used to determine the apoptosis of macrophages in vulnerable plaques in the aortic root of mice in the two groups.Western blotting was used to detect the expression levels of p-PERK,CHOP,Caspase-3 and Caspase-9 proteins in the diseased tissues of the two groups.Results Compared with the control group,the AS plaque area in the aortic root of the mice in the experimental group de‐creased,the number of Mac decreased,and the apoptosis index of Mac decreased(all P<0.05).Compared with the con‐trol group,the expression levels of PERK,CHOP,Caspase-9 and Caspase-3 proteins in the aortic root tissue of mice in the experimental group decreased(all P<0.05).Conclusion Curcumin has the effect of stabilizing atherosclerotic vul‐nerable plaques in ApoE^(-/-)mice,and it plays a role by inhibiting the apoptosis-related ERS-PERK-CHOP pathway.

关 键 词：姜黄素 动脉粥样硬化斑块 动脉粥样硬化 细胞凋亡 巨噬细胞凋亡 内质网应激 

分 类 号：R543[医药卫生—心血管疾病]