丹蒌片对ApoE基因敲除小鼠动脉粥样硬化的疗效研究  

Effects of Danlou Tablet on Atherosclerosis in ApoE-gene Knockout Mice

作　　者：缪静 周鑫斌[2] 毛威[2] 陈洁[2] MIAO Jing;ZHOU Xin-bin;MAO Wei;CHEN Jie(Department of Critical Care Medicine,Sir Run Run Shaw Hospital,Zhejiang University School of Medicine,Hangzhou,310016;Department of Cardiology,First Affiliated Hospital of Zhejiang Chinese Medical University,Hangzhou,310006)

机构地区：[1]浙江大学医学院附属邵逸夫医院重症医学科,杭州310016 [2]浙江中医药大学附属第一医院心内科,杭州310006

出　　处：《中国中西医结合杂志》2020年第11期1367-1372,共6页Chinese Journal of Integrated Traditional and Western Medicine

基　　金：浙江省教育厅科研项目(No.Y201327471);浙江省中医药科技计划项目(No.2014ZB043)。

摘　　要：目的观察丹蒌片对ApoE基因敲除(ApoE-/-)小鼠动脉粥样硬化(AS)的作用。方法32只雄性ApoE-/-小鼠随机分为空白组、模型组、他汀组、丹蒌组,每组8只。空白组喂饲基础饲料,余各组采用高糖高脂饲料连续喂饲12周制备AS模型。模型组、他汀组及丹蒌组于第5周时分别给予生理盐水、阿托伐他汀混悬液(1.5 mg/mL)、丹蒌片混悬液(0.34 mg/mL)连续灌胃干预8周。干预结束后,ELISA检测血清血脂、一氧化氮(NO)、内皮素(ET)及IL-6含量;油红“O”染色观察主动脉内膜斑块;HE染色观察小鼠主动脉内膜厚度及斑块面积;透射电镜观察血管平滑肌细胞(VSMC)结构。结果与空白组比较,模型组血清TC、TG、LDL-C、IL-6、ET水平、内膜厚度、面积及内/中膜厚度面积比升高(P<0.05,P<0.01),HDL-C、NO水平下降(P<0.05,P<0.01)。与模型组比较,他汀组和丹蒌组血清TC、TG、LDL-C、ET水平、内膜厚度、面积及内/中膜厚度面积比下降(P<0.05,P<0.01),NO水平升高(P<0.05,P<0.01),丹蒌组血清IL-6水平下降(P<0.01)。模型组油红“O”染色AS区域脂肪呈鲜红色,形成广泛而典型的AS成熟斑块,透射电镜下可见VSMC胞浆内有较多的吞噬大量脂质形成的空泡,细胞间胶原纤维增生明显,呈典型合成型改变,他汀组和丹蒌组AS脂肪区域面积减少,主动脉合成型VSMC减少。结论丹蒌片可显著降低血清血脂、炎症因子水平,保护血管内皮功能,抑制VSMC异常增殖,从而延缓AS的发生发展。Objective To observe the effect of Danlou Tablet(DLT)on atherosclerosis(AS)in ApoEgene knockout(ApoE-/-)mice.Methods Totally 32 male ApoE-/-mice were randomly divided into 4 groups,blank group,model group,atorvastatin group,DLT group,8 in each group.Mice in the control group were given basic forage,while mice in the other three groups were given high fat forage 12 weeks to establish AS model.Then mice in the model group,atorvastatin group and DLT group were administered with normal saline,atorvastatin suspension(1.5 mg/mL),and DLT suspension(0.34 g/mL)by gastrogavage respectively from 5 th week to 12 th week.After intervention,serum blood lipids,nitric oxide(NO),endothelin(ET)and IL-6 levels were tested by ELISA.Intimal plaque in aorta was observed by oil red O staining.Intima thickness and area in aorta were observed by HE staining.The vascular smooth muscle cell(VSMC)structure was tested by transmission electron microscope(TEM).Results Compared with the blank group,the serum levels of TC,TG,LDL-C,IL-6,ET,intima thickeness and area,intima/medial membrane thickness and area ratio increased(P<0.05,P<0.01),levels of HDL-C and NO decreased(P<0.05,P<0.01)in the model group.Compared with the model group,the serum levels of TC,TG,LDL-C,ET,intima thickeness and area,intima/medial membrane thickness and area ratio decreased(P<0.05,P<0.01),level of NO increased(P<0.05,P<0.01)in atorvastatin and DLT group,while the serum level of IL-6 decreased(P<0.01)in DLT group.The fat of AS region stained by oil red O in model group was bright red,and it forming extensive and typical AS mature plaques.TEM showed that there were large number of vacuoles in the cytoplasm of VSMC which engulfed much lipids.The proliferation of intercellular collagen fibers was obvious,which showed typical synthetic changes.Compared with the model group,the area of AS fat area and number of VSMC in atorvastatin and DLT groups decreased.Conclusion DLT can prevent the genesis and development of AS through lowering the plasma blood lipids and inflammatory fac

关 键 词：丹蒌片 APOE基因敲除小鼠 动脉粥样硬化 

分 类 号：R285.5[医药卫生—中药学]