丹参酮ⅡA通过5-脂氧酶/白三烯通路治疗动脉粥样硬化的作用机制研究  

Clinical Effects and Mechanism of TanshinoneⅡA in the Treatment of Atherosclerosis through 5-Lipoxygenase/Leukotriene

作　　者：何德全 陈友权[1] HE Dequan;CHEN Youquan(Third Affiliated Hospital of Guangzhou Medical University,Guangzhou 510150,Guangdong,China)

机构地区：[1]广州医科大学附属第三医院,广州510150

出　　处：《中西医结合心脑血管病杂志》2020年第23期3959-3962,3967,共5页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：广东省中医药局科研课题(No.20191211)。

摘　　要：目的探讨丹参酮ⅡA通过5-脂氧酶(5-LO)/白三烯通路改善动脉粥样硬化(AS)的作用机制。方法以体质量180~220 g SD大鼠45只为研究对象,随机分为对照组、AS模型组、丹参酮ⅡA组;苏木精-伊红(HE)染色观察腹主动脉内膜病理表现情况,全自动生化分析仪检测各组大鼠血清中总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)含量变化;酶联免疫吸附法检测各组大鼠血清中5-LO、白三烯B4(LTB4)和白三烯C4(LTC4)含量变化;免疫组化法测定各组大鼠腹主动脉中5-LO阳性的表达情况;实时荧光定量聚合酶链式反应(qPCR)和蛋白质印迹法(Western Blot)法检测各组大鼠腹主动脉中5-LO、白三烯A4H(LTA4H)和LTB4 mRNA和蛋白的表达。结果与对照组比较,AS模型组大鼠腹主动脉出现明显的AS病理变化,表明AS造模成功;与对照组比较,AS模型组大鼠血液中TC、TG和LDL含量均增加(P<0.05),HDL含量减少(P<0.05),与AS模型组比较,丹参酮ⅡA组大鼠血液中TC、TG和LDL含量均减少(P<0.05),HDL含量增加(P<0.05);与对照组比较,AS模型组大鼠血清中5-LO、LTB4和LTC4含量均增加(P<0.05),与AS模型组比较,丹参酮ⅡA组大鼠血清中5-LO、LTB4和LTC4含量均减少(P<0.05);与对照组比较,AS模型组大鼠主动脉中5-LO、LTA4H和LTB4 mRNA和蛋白表达均上调(P<0.05),与AS模型组比较,丹参酮ⅡA组大鼠主动脉中5-LO、LTA4H和LTB4 mRNA蛋白表达均下调(P<0.05);对照组动脉管壁均匀,为淡蓝色浅染,AS模型组动脉管壁周围棕黄色深染,丹参酮ⅡA组管壁内膜脂质浸润较AS模型组轻。结论丹参酮ⅡA抑制5-LO/白三烯通路的活化,从而发挥抗AS的作用。Objective To investigate clinical effects and mechanism of tanshinoneⅡA in the treatment of atherosclerosis through 5-lipoxygenase/leukotriene pathway.Methods SD rats were randomly divided into control group,AS model group and tanshinoneⅡA group.HE staining was used to observe the pathological manifestations of the intima of the abdominal aorta.The contents of total cholesterol(TC),triglyceride(TG),low density lipoprotein(LDL),high density lipoprotein(HDL)in each group were detected by automatic biochemical analyzer.The levels of 5-LO,Leukotriene B4(LTB4)and Leukotriene C4(LTC4)in each group were detected by enzyme-linked immunosorbent assay.The expression of 5-LO positive in the abdominal aorta was determined by immunohistochemistry.The expressions of 5-LO,LTA4H and LTB4 mRNA and protein in abdominal aorta were detected by qPCR and Western Blotting.Results Compared with the control group,the AS model group showed obvious AS pathological changes in the abdominal aorta,indicating that the AS model was successfully replicated.Compared with the control group,the levels of TC,TG and LDL in the blood of the AS model group increased(P<0.05)and the HDL content decreased(P<0.05).Compared with the AS model group,the levels of TC,TG and LDL in the blood of the tanshinoneⅡA group decreased(P<0.05),and the HDL content was increased(P<0.05).Compared with the control group,the levels of 5-LO,LTB4 and LTC4 in the AS model group were increased(P<0.05).Compared with the AS model group,the levels of 5-LO,LTB4 and LTC4 in the tanshinoneⅡA group were creased(P<0.05);Compared with the control group,the mRNA and protein expressions of 5-LO,LTA4H and LTB4 in the aorta of the AS model group were up-regulated(P<0.05).Compared with the AS model group,the mRNA and protein expressions of 5-LO,LTA4H and LTB4 in the aorta of the tanshinoneⅡA group were down-regulated(P<0.05).The arterial wall in the control group was uniform and light blue stained,and the arterial wall in the AS model group was surrounded by brownish yellow and deep

关 键 词：动脉粥样硬化 丹参酮ⅡA 5-脂氧酶 白三烯 实验研究 

分 类 号：R543[医药卫生—心血管疾病] R285.5[医药卫生—内科学]