三七总皂苷抗动脉粥样硬化作用的实验研究  

Effect of Panax Notoginseng Saponins in Attenuating Atherosclerosis

作　　者：熊敏琪[1] 崔金刚[1] 陈瑜[1] 张腾[1] XIONG Minqi;CUI Jingang;ZHANG Teng;CHEN Yu(Yueyang Hospital of Integrated Chinese-Western Medicine Affiliated to Shanghai Chinese Medicine University,Clinical Institute of Integrative Chinese-Western Medicine of Shanghai Academy of Chinese Medicine,Shanghai 20043)

机构地区：[1]上海中医药大学附属岳阳中西医结合医院,上海市中医药研究院中西医结合临床研究所,上海200437

出　　处：《中国中医药科技》2018年第5期656-660,共5页Chinese Journal of Traditional Medical Science and Technology

基　　金：上海市东方学者跟踪计划(GZ2015011);上海市优秀学术带头人(1XD1403500);上海市高校特聘教授(东方学者)人才计划(沪教委人[2010]84号;沪教委人[2011]88号);上海市085一流学科建设科技创新支持计划(085ZY1212;085ZY1221);上海市曙光计划(13SG42);国家中医药管理局中西医结合临床重点学科建设项目(国中医药发[2009]30号)

摘　　要：目的:探讨三七总皂苷抗动脉粥样硬化的效应。方法:在体动物实验:以Apo E基因敲除(ApoE^(-/-))小鼠为研究对象,喂饲高脂饲料模拟动脉粥样硬化发病过程,将9周龄ApoE^(-/-)小鼠随机分为模型组、PNS低剂量组(50 mg/kg)、PNS中剂量组(100 mg/kg)、PNS高剂量组(200 mg/kg)。接受溶剂治疗的C57BL/6J小鼠及ApoE^(-/-)小鼠分别作为正常对照及模型对照组,腹腔注射进行干预8周。通过H&E染色、Masson’s trichrome染色和油红O染色分别观察主动脉病理形态学改变、血管纤维化及脂质沉积。体外细胞学实验:用LPS诱导小鼠巨噬细胞系RAW264.7细胞产生炎症反应和氧化应激,用不同浓度的PNS进行干预(50、100、200、400 mg/L),采用Real Time-PCR测定RAW264.7细胞炎症相关因子(IL1-β、IL-6、TNF-α和ICAM1)和氧化应激相关基因(Nrf2、HO-1、SOD1和SOD2)的表达水平。结果:主动脉H&E染色、油红O染色和Masson’s trichrome染色结果显示,与模型组比较,PNS低、中、高剂量均能不同程度减小斑块面积、减少斑块上的脂质沉积和减小斑块纤维化面积(P<0.05)。Real timePCR结果显示:与空白组对比,模型组的炎症相关基因IL-1β、IL-6、TNF-α和ICAM1的表达显著上调(P<0.01),氧化应激相关基因Nrf2、HO-1和SOD1的表达无差异,仅SOD2的表达有反应性上调(P<0.01);与模型组对比,PNS各浓度均能显著下调IL-1β、IL-6、TNF-α和ICAM1的表达(P<0.01),不同程度上调Nrf2、HO-1、SOD1和SOD2的表达(P<0.05或P<0.01)。结论:三七总皂苷具有体内抗动脉粥样硬化斑块形成作用和显著的体外抗炎、抗氧化作用。Objective： To explore the effects of Panax Notoginseng Saponins in attenuating atherosclerosis.Methods： In vivo experiment： Apo E deficient（ ApoE^（-/-）） m ice fed with high fat diet which spontaneously develop atherosclerotic lesions recapitulating human pathologies. ApoE^（-/-）mice were randomly divided to model group and PNS grouse at the dose of 50,100,200 mg/kg bw. C57 BL/6 J wild type mice were included as normal control and treated with vehicle,the treatment was delivered by intraperitoneal injection for 8 weeks. HE staining,Oil Red O staining and Masson＇s trichrome staining were performed to characterize the gross morphology,fibrosis and lipid deposition in the aorta. In vitro experiment： RAW264. 7 cells were challenged with LPS to induce inflammation and oxidative stress,PNS was applied at 50,100,200,400 mg/L,the expressions of genes encoding proinflammatory cytokines（ IL-1β,I L-6,TNF-α,I CAM1） and oxidative stress-related genes such as Nrf2,HO-1,SOD1,SOD2 were examined by real time-PCR. Results： HE staining,Oil Red O staining and Masson ＇s trichrome staining revealed significant attenuation of atherosclerotic development,lipid deposition and artery intimal fibrosis as a result of PNS treatment in ApoE^（-/-）mice compared to that from vehicle-treated ApoE^（-/-）mice（ P〈0. 05）. Real time-PCR analysis showed that compared to that from vehicle-treated cells in the absence of LPS incubation,the mRNA expression levels of IL-1β,I-L6,TNF-α and ICAM1 were significantly increased in the RAW264. 7 cells in response to LPS incubation（ P〈0. 01）.No significant changes were observed in the mRNA expression levels of Nrf2,HO-1 and SOD1 as a result of LPS incubation,but increased level of SOD2 was observed（ P〈0. 01）. In contrast,significantly decreased expressions of IL1-β,IL-6,TNF-αand ICAM1（ P〈0. 01） and increased expression of Nrf2,HO-1,SOD1,SOD2（ P〈0. 05 or P〈0. 01） were observed in LPS-challenged cells treated with PNS.-Conclusions： PNS can at

关 键 词：三七总皂苷 动脉粥样硬化 炎症因子 氧化应激 小鼠 巨噬细胞 体内实验 体外实验 

分 类 号：R285.5[医药卫生—中药学]