补阳还五汤对动脉粥样硬化家兔自噬及炎症反应的影响  

Effect of Buyang Huanwu Tang on Autophagy and Inflammation in Atherosclerotic Rabbits

作　　者：赖莎 蒋永和 陈碧珊[1] 洪燕萍[1] 吴荣佳 潘芸芸 LAI Sha;JIANG Yonghe;CHEN Bishan;HONG Yanping;WU Rongjia;PAN Yunyun(The First Afiliated Hospital of Guangdong Pharmaceutical University,Guangzhou 510080 Guangdong,China;Guangzhou Dong Sheng Hospital,Guangzhou 510140 Guangdong,China)

机构地区：[1]广东药科大学附属第一医院,广东广州510080 [2]广州市东升医院,广东广州510140

出　　处：《中药新药与临床药理》2020年第4期391-395,共5页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：国家自然科学基金青年科学基金项目(81603526);广东省中医药局科研项目(20182078)。

摘　　要：目的探讨补阳还五汤对动脉粥样硬化(AS)家兔自噬及炎症反应的影响。方法将60只新西兰白兔给予普通饲料适应性喂养1周后,随机分为空白对照组、模型组、辛伐他汀组(5 mg·kg-1)及补阳还五汤低、中、高剂量组(5、10、20 g·kg-1)。采用高脂饮食连续喂养12周建立动脉粥样硬化家兔模型;同时按照设定剂量灌胃给药,每日1次,连续给药12周。采用透射电镜观察AS家兔主动脉斑块内自噬体形成情况;油红O染色后进行主动脉组织病理学观察及斑块面积测定;采用全自动生化分析仪检测家兔血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)含量;采用ELISA法检测家兔血清中一氧化氮(NO)、内皮型一氧化氮合酶(eNOS)、肿瘤坏死因子(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)水平。结果与空白对照组比较,模型组家兔的主动脉斑块面积百分比显著升高(P<0.05),主动脉斑块内自噬体形成减少;TC、TG、LDL-C水平均明显升高(P<0.05),而HDL-C水平明显降低(P<0.05);NO、eNOS水平明显降低(P<0.05),TNF-α、IL-1β、IL-6水平明显升高(P<0.05)。与模型组比较,各给药组家兔的主动脉斑块面积百分比显著降低(P<0.05),补阳还五汤中、高剂量组的自噬体形成增多;各给药组家兔的TC、TG水平均明显降低(P<0.05);补阳还五汤中、高剂量组的LDL-C水平明显降低,HDL-C水平明显升高,差异均有统计学意义(P<0.05);各给药组家兔的NO、eNOS水平明显升高(P<0.05),TNF-α、IL-1β、IL-6水平均明显降低(P<0.05)。结论补阳还五汤可能通过调节斑块内细胞自噬水平,调节eNOS活化,诱导NO释放,并减少炎症因子的释放,降低动脉硬化斑块面积,降低血脂水平,从而达到抗动脉粥样硬化的作用。Objective To explore the anti-atherosclerosis(AS)mechanism of Buyang Huanwu Tang(BYHWT)andits effect on autophagy and inflammation in rabbits. Methods Sixty SPF-grade New Zealand white rabbits aged 2 months were fed with common diet for 1 week. The rabbits were randomly divided into blank control group,modelgroup, simvastatin(5 mg · kg-1) group and BYHWT low, medium, high dose groups(5, 10, 20 g · kg-1,respectively). The control group was fed with normal diet,and the rest were fed with internationally recognized high-fat diet for 12 weeks. The AS rabbits were given drugs orally once a day for 12 weeks. The area and autophagy ofaortic plaque were observed. The level of blood lipid was measured. Levels of nitric oxide(NO),endothelial nitricoxide synthase(eNOS)and related inflammatory factors in serum were determined by ELISA. Results Compared with the blank control group,the area persentage of AS plaque,the levels of blood lipid,serum tumor necrosisfactor(TNF-α),interleukin-1β(IL-1β)and interleukin-6(IL-6)increased significantly(P < 0.05),autophagyformation and the serum levels of NO and eNOS decreased in the model group(P < 0.05). Compared with the modelgroup,the plaque area persentage of simvastatin group and BYHWT medium and high groups decreased significantlyand the autophagy formation increased(P < 0.05). The blood lipid levels decreased significantly(P < 0.05). Theserum levels of NO and eNOS increased(P < 0.05),but contents of TNF-α,IL-1β and IL-6 decreased significantly(P < 0.05). Conclusion BYHWT can significantly reduce the area of atherosclerotic plaque,the levels of TC,TGand LDL-C and increase the level of HDL-C by regulating the level of autophagy and the activation of eNOS,inducing the release of NO,and reducing the release of inflammatory factors.

关 键 词：补阳还五汤 动脉粥样硬化 血脂 炎症因子 一氧化氮 内皮型一氧化氮合酶 自噬 家兔 

分 类 号：R285.5[医药卫生—中药学]