活血方与阳和汤抗apoE^(-/-)小鼠动脉粥样硬化并发非酒精性脂肪肝的比较研究  

Comparative Study on the Anti Atherosclerosis Function of Huoxue Recipe and Yang He Decoction in apoE^(-/-) Mice Combined with Nonalcoholic Fatty Liver Disease

作　　者：姜楠[1] 袁晓雯[1] 薛欣[1] 陶旭光[1] 乔艳雪 李蕊[2,3] 陈冰 李玉梅[1] 胡镜清[1] 马雅銮[1] 

机构地区：[1]中国中医科学院中医基础理论研究所,北京100700 [2]首都医科大学附属北京地坛医院传染病研究所,北京100015 [3]新发突发传染病研究北京市重点实验室,北京100015

出　　处：《中国中医基础医学杂志》2017年第12期1705-1709,1735,共6页JOURNAL OF BASIC CHINESE MEDICINE

基　　金：国家重点基础研究发展计划(973)(2014CB542903)-中医证候临床辨证的基础研究;中国中医科学院自主选题研究项目(YZ-1407;YZ-1702)-祛痰;化瘀及祛痰化瘀对ApoE-/-动脉粥样硬化小鼠作用机制的对比研究;基于黄连解毒汤调控肠道菌群失衡抗动脉粥样硬化的机制研究

摘　　要：目的:观察活血方与阳与汤对高脂饮食导致动脉粥样硬化并发非酒精性脂肪肝的apoE^(-/-)小鼠全身、主动脉血管和肝脏免疫反应的影响。方法:10周龄雌性apoE^(-/-)小鼠给予高脂饮食,治疗组同时给予活血方或阳和汤干预18周,检测血脂肝功能水平、血浆细胞因子、外周血单核细胞比例、单核细胞亚型比例及其表面受体TLR4的表达、主动脉和肝脏的病理变化及炎性细胞因子表达。结果:18周高脂饮食导致apoE^(-/-)小鼠外周血TC和LDL水平显著增高,肝功能ALT和AST水平没有明显改变,外周血单核细胞比例、单核细胞炎症亚型Ly6C++及其表面受体TLR4的表达显著升高,血浆细胞因子IL-10、IL-1b、MCP-1、M-CSF和TNF-a水平升高;模型组小鼠主动脉血管检测到明显的AS斑块,肝脏油红O染色阳性;主动脉组织炎症因子TNF-a、MCP-1、IFN-γ、NOS2和IL-1b表达显著升高,肝组织炎症因子TNF-a、IL-6、MCP-1、IFN-γ、NOS2和IL-1b表达显著升高。18周的中药活血方和阳和汤干预并未引起血脂明显改善,肝功能ALT和AST水平也没有明显变化;但活血方降低外周血单核细胞及其Ly6C++亚型比例,活血方和阳和汤降低核细胞及其Ly6C++表面受体TLR4表达;对于血浆炎症因子,活血方降低IL-10、IL-1b、MCP-1和TNF-a水平,显著减低M-CSF水平,阳和汤仅对TNF-a水平略有降低;活血方和阳和汤干预18周肝脏油红O染色较模型组弱,活血方较阳和汤减弱更为显著。主动脉血管和肝脏实时定量PCR检测发现,活血方和阳和汤明显减低炎症因子TNF-a、MCP-1、IFN-γ、NOS2和IL-1b表达,活血方降低效果更为显著。结论:长期高脂饮食导致apoE^(-/-)小鼠动脉粥样硬化并发非酒精性脂肪肝,引发机体全身性炎症反应及主动脉血管和肝脏局部炎症反应。中药活血方和阳和汤通过不同机制、不同程度地抑制炎症反应,以独立于降脂作用的方式,调节高脂血症引发全身炎症反应�Objective： To observe and compare the effect of Huoxue-Fang and Yanghe-Decoction on AS and NAFLD of apoE-deficient mice with Western diet （WD） by modulating systemic immune responses, liver and aortic immune responses. Methods： In the present study, 10 week-old homozygous female apoE^-/- mice were fed with a normal chow diet, a high cholesterol WD and WD supplemented with Huoxue-Fang and Yanghe-Decoction. After 18 weeks, the proportions of monocyte and subtypes of monocyte, and their surface receptor TLR4 in peripheral blood were detected by flow cytometry. Serum cytokines were detected by suspension array technology. The pathogenesis of aorta was detected by HE staining, the pathogenesis liver was detected by Oil-Red O staining and cytokiues in aorta and liver were detected by real-time PCR. Results： 18-week WD increased the levels of TC and LDL in apoE^-/- mice. Hyperlipidemia increased the proportions of monocyte and Ly6C^＋＋ , and expression of their surface receptor TLR4 in apoE^ -/- mice; and induced serum IL-10, IL-1b, MCP-1, M-CSF and TNF-a levels. In aorta, 18-week WD induced atherosclerosis lesions of aorta in apoE^-/- mice, increased expressions of cytokines TNF-a, MCP-1, IFN-γ, NOS2 and IL-lb expression. In liver, 18-week WD induced NAFLD in apoE^-/- mice, increased expressions of cytokines TNF-α, IL-6, MCP-1, IFN-γ, NOS2 and IL-lb expression. After 18 weeks admistration of Houxue-Fang, Yanghe-Decoction on ApoE -/- mice with WD, these medicines did not change the serum lipid levels significantly. Houxue-Fang decreased the proportions of monocyte and Ly6C^＋＋. Huoxue-Fang and Yanghe-Decoction decreased TLR4expression in monocyte and Ly6C^＋＋ Huoxue-Fang lowered serum IL- 10, IL-lb, MCP-1, TNF-a and M-CSF level, and Yanghe-Decoction just decreased TNF-α level. In liver, Huoxue-Fang and Yanghe-Decoction decreased steatosis. Huoxue-Fang and Yanghe-Decoction decreased expressions of cytokines TNF-α, MCP-1, IFN-γ, NOS2 and IL-1b in aorta and liver. And Huoxue-Fang showed more effect

关 键 词：动脉粥样硬化 非酒精性脂肪肝 炎症 活血方 阳和汤 

分 类 号：R585.5[医药卫生—内分泌]