通瘀煎对ApoE基因敲除小鼠动脉粥样硬化斑块形成的影响及机制  

Effect and mechanism of Tongyu decoction on atherosclerotic plaque formation in ApoE knockout mice

作　　者：卢素宏 姚丽梅[1] 刘瑶[1] 杨雅琴[1] 林华景[1] LU Su-Hong;YAO Li-Mei;LIU Yao(Guangdong Food and Drug Vocational College,Guangzhou 510520,Guangdong,China)

机构地区：[1]广东食品药品职业学院,广东广州510520

出　　处：《中国老年学杂志》2020年第8期1745-1750,共6页Chinese Journal of Gerontology

基　　金：广东省中医药局科研项目(20172024);广东省医学科学技术研究基金项目(A2017401)。

摘　　要：目的探讨通瘀煎对ApoE基因敲除小鼠动脉粥样硬化斑块形成的影响及其作用机制。方法50只ApoE基因敲除小鼠随机分为模型组、阳性药物组(立普妥组)、通瘀煎低、中、高剂量组各10只,以高脂饲料喂养12 w构建动脉粥样硬化模型。另取10只C57BL/6雄性小鼠为空白组,普通饲料喂养。立普妥组给予立普妥5 mg/(kg·d)灌胃,通瘀煎低、中、高剂量组分别以6.5、13.0、26.0 g/(kg·d)剂量灌胃给药,空白组和模型组以等量生理盐水灌胃。末次给药后,处死取材。苏木素-伊红(HE)染色观察主动脉管腔内粥样斑块;透射电镜摄片观察主动脉管腔内的超微结构变化;酶联免疫吸附试验检测血脂、血液流变学、黏附分子、主动脉组织炎症因子的含量;Western印迹法检测主动脉内细胞内信号传导及转录活化子(STAT)3、磷酸化(p)-STAT3、细胞因子信号转导抑制蛋白(SOCS)1的蛋白表达。结果与空白组相比,模型组主动脉病变相对面积、血脂水平、黏附分子及炎症因子含量显著增加(P<0.01);与模型组相比,立普妥组、通瘀煎低、中、高剂量组主动脉病变相对面积明显降低(P<0.01,P<0.05);通瘀煎高剂量组血脂水平、黏附分子、炎症因子含量、p-STAT3蛋白表达均明显降低,而STAT3、SOCS1的蛋白含量明显升高(均P<0.01)。结论通瘀煎能有效抑制ApoE基因敲除小鼠动脉粥样硬化斑块的形成,其机制可能通过降脂、抑制黏附分子聚集、减少炎症反应,抑制增生信号通路白细胞介素-6/STAT3的激活,有效保护主动脉血管壁,从而发挥抗动脉粥样硬化作用。Objective To investigate the effect of Tongyu decoction on atherosclerotic plaque formation in ApoE knockout mice and its mechanism.Methods Fifty ApoE knockout mice were randomly divided into model,positive drug,low,medium and high dose Tongyu decoction groups,10 mice in each group.Atherosclerosis model was established by feeding high-fat diet for 12 weeks.Another 10 C57BL/6 male mice were taken into blank control group and fed with normal feed.The positive drug group was given lipitor at 5 mg/(kg·d),while the Tongyu decoction group at 6.5 g/(kg·d),13 g/(kg·d)and 26 g/(kg·d)respectively.The blank control group and the model group were given normal saline at the same volume.After the last administration,mice were sacrificed for samples.Atherosclerotic plaques were observed by HE staining in the active vascular lumen of mice.Transmission electron microscopy was used to observe the ultrastructural changes in the active vascular lumen of mice.The contents of serum lipids,hemorheology,adhesion molecules and inflammatory factors in aortic tissue were determined by ELISA.Protein expressions of STAT3,p-STAT3 and SOCS1 in aorta were detected by Western blot.Results Compared with the blank group,the relative area of aortic lesions,blood lipid level,adhesion molecules and inflammatory factors in mice of the model group were significantly increased(P<0.01).Compared with the model group,the relative area of aortic lesions was significantly reduced in the lipitor group,the Tongyu decoction group,the medium and high dose groups(P<0.01 or P<0.05).Compared with the model group,the levels of blood lipid,adhesion molecules,inflammatory factors and p-STAT3 protein expression were significantly decreased,while the protein levels of STAT3 and SOCS1 were significantly increased in the high dose group of Tongyu decoction(P<0.01).Conclusions Tongyu decoction could effectively inhibit the formation of atherosclerotic plaques in ApoE knockout mice.Its mechanism might be to reduce lipid,inhibit adhesion molecule aggregation,reduce infla

关 键 词：通瘀煎 脂质代谢 炎症反应 白细胞介素-6/细胞内信号传导及转录活化子3 

分 类 号：R285.5[医药卫生—中药学]