姜黄素对ApoE^(-/-)小鼠动脉粥样硬化病变的影响及机制

Study on the effect and mechanism of curcumin on atherosclerosis in ApoE^(-/-)mice

目的研究姜黄素对ApoE基因敲除(ApoE^(-/-))小鼠的动脉粥样硬化(Atherosclerosis,AS)病变的影响及机制。方法取SPF级雄性ApoE^(-/-)小鼠(4周龄)12只,随机分为:空白组(给予高脂饲料饮食+等量1%羧甲基纤维素钠灌胃)、低浓度姜黄素组[给予高脂饮食+姜黄素30 mg/(kg·d)灌胃]、高浓度姜黄素组[给予高脂饮食+姜黄素200 mg/(kg·d)灌胃],连续喂养8周;全自动生化仪检测血清总胆固醇(Total cholesterol,TC)、甘油三酯(Triglyceride,TG),低密度脂蛋白胆固醇(Low-Density Lipoprotein Cholesterol,LDL-C)水平;苏木素-伊红(HE)对主动脉弓染色并进行观察;聚合酶链式反应(Real-timeQuantitativepolymerase chain reaction,RT-qPCR)检测M1巨噬细胞主要标记物诱导型一氧化氮合酶(Inducible nitric oxide synthase,iNOS)和M2巨噬细胞主要标记物精氨酸酶-1(Arginase-1,Arg-1),白细胞介素-10(Interleukin,IL-10),以及核因子-κB(Nuclear Factor-κB,NF-κB)表达水平。结果与空白组相比,高浓度姜黄素组TC、LDL-C水平均降低,差异有统计学意义(P<0.05),低浓度姜黄素组差异无统计学意义;与空白组相比,高浓度姜黄素能够减轻动脉粥样硬化,减少动脉粥样硬化面积(P<0.05),而低浓度姜黄素组差异无统计学意义;与空白组相比,高浓度姜黄素下调动脉粥样硬化斑块中iNOS、NF-κB基因表达(P<0.05),上调Arg-1、IL-10基因表达(P<0.05),而低浓度姜黄素组差异无统计学意义。结论姜黄素可能通过MAPK/NF-κB通路抑制动脉粥样硬化斑块组织炎症反应,调控巨噬细胞向M2方向极化,增加动脉粥样硬化斑块稳定性。

Objective To investigate the effect and mechanism of curcumin on Atherosclerosis(AS)lesions in ApoE^(-/-)knockout mice.Methods 12 SPF male ApoE^(-/-)mice(4 weeks of age)were randomly divided into blank group,low concentration curcumin group and high concentration curcumin group.Automatic biochemical analyzer was used to measure serum levels of total cholesterol(TC),triglyceride(TG)and Low-density lipoprotein cholesterol(LDL-C).The aortic arch was stained with Hematoxylin-eosin(HE)and was observed.Real-time quantitative polymerase chain reaction(RT-qPCR)was used to detect the main markers such as M1 macrophages Inducible nitric oxide Expression levels of synthase(iNOS),Arginase-1(Arg-1),Interleukin(IL-10),and Nuclear factor-κB(NF-κB)in M2 macrophages.Results Compared with the blank group,TC and LDL-C levels in the high-concentration curcumin group were decreased with statistical significance(P<0.05),while there was no statistical significance in the low-concentration curcumin group.Compared with the blank group,HE staining results showed that high concentration of curcumin could reduce atherosclerosis and the area of atherosclerosis(P<0.05).There was no statistical significance in the low concentration curcumin group.Compared with the blank group,RT-qPCR results showed that the expression levels of iNOS and NF-κB genes in atherosclerotic plaques in high concentration curcumin group were decreased(P<0.05),and the expression levels of Arg-1 and IL-10 genes were increased(P<0.05),but there was no statistical significance in low concentration curcumin group.Conclusion In this study,we found curcumin can inhibit the inflammatory response of atherosclerotic plaque tissue through the MAPK/NF-κB pathway,regulate the polarization of macrophages to M2 direction,and increase the stability of atherosclerotic plaque.