丹蒌片与血府逐瘀颗粒对ApoE^(-/-)小鼠动脉粥样硬化斑块影响的比较研究  

Effects of Danlou Tablet and Xuefu Zhuyu Granule on Atherosclerotic Plaques 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,Si 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》2021年第5期577-582,共6页Chinese Journal of Integrated Traditional and Western Medicine

基　　金：浙江省基础公益计划项目(No.LGF19H020003);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：目的比较丹蒌片与血府逐瘀颗粒对ApoE基因敲除(ApoE^(-/-))小鼠动脉粥样硬化(AS)斑块的影响。方法40只雄性ApoE^(-/-)小鼠随机分为正常组、模型组、他汀组、丹蒌组和血府组,每组8只。正常组ApoE^(-/-)小鼠喂食基础饲料12周,余各组均采用高糖高脂饮食制备AS模型。模型组、他汀组、丹蒌组、血府组分别给予生理盐水、阿托伐他汀片混悬液(1.5 mg/mL)、丹蒌片混悬液(0.34 g/mL)、血府逐瘀颗粒混悬液(0.64 g/mL)灌胃干预8周。干预结束后,ELISA检测各组血脂、ox-LDL、内皮素(ET-1)、IL-6及TNF-α含量;油红"O"染色观察主动脉内膜斑块;HE染色观察主动脉病理形态学改变,并计算内膜厚度及斑块面积;透射电镜观察主动脉血管平滑肌细胞(VS M C)超微结构改变。结果与正常组比较,模型组血清TC、TG、LDL-C、ox-LDL、ET-1、IL-6和TNF-α水平升高(P<0.01,P<0.05),HDL-C水平下降(P<0.05),油红"O"染色A S区域脂肪呈鲜红色,形成广泛而典型的A S成熟斑块,H E染色内膜增厚,斑块面积增大,透射电镜下可见VSMC胞浆内肌丝减少,粗面内质网、线粒体等细胞器增多,有较多脂滴形成,呈典型合成型改变;与模型组比较,他汀组和丹蒌组血清TC、TG、LDL-C、ox-LDL、ET-1和IL-6水平下降(P<0.05,P<0.01),HDL-C水平升高(P<0.05),TNF-α有下降趋势,但差异无统计学意义(P>0.05),血府组TC、TG、ox-LDL、ET-1和IL-6水平下降(P<0.05,P<0.01),LDL-C、TNF-α下降及HDL-C升高差异无统计学意义(P>0.05)。油红"O"染色可见各给药组主动脉亦有呈鲜红色的AS斑块,但AS脂肪区域面积明显减小,HE染色可见内膜增厚及斑块面积明显减小,透射电镜下可见各给药组中膜合成型VSMC较模型组明显减少。结论丹蒌片和血府逐瘀颗粒均可降低AS模型ApoE^(-/-)小鼠炎症因子的表达及稳定AS斑块,但丹蒌片调节血脂代谢异常的作用优于血府逐瘀颗粒。Objective To compare the effect of Danlou Tablet and Xuefu Zhuyu Granule on atherosclerotic plaques in ApoE-gene knockout(ApoE^(-/-))mice with atherosclerosis(AS).Methods Forty male ApoE^(-/-)mice were randomly divided into five groups,i.e.,the control group,the model group,the Atorvastatin group,the Danlou group,the Xuefu group,8 in each group.Mice in the control group were given basic forage for 12 weeks,while mice in the other four groups were given with high fat forage to build AS model.Then mice in the model group,the Atorvastatin group,the Danlou group,the Xuefu group were administered with normal saline,Atorvastatin suspension(1.5 mg/mL),Danlou Tablet suspension(0.34 g/mL)and Xuefu Zhuyu Granule suspension(0.64 g/mL)by gastrogavage for 8 successive weeks,respectively.After intervention,serum blood lipids,oxidized low-density lipoprotein(ox-LDL),endothelin1(ET-1),IL-6 and TNF-αlevels were detected by ELISA.Intimal plaque in aorta was observed by oil red"O"staining.The pathological changes,intima thickness and area in aorta were observed by HE staining.The vascular smooth muscle cell(VSMC)ultrastructure was detected by transmission electron microscope(TEM).Results Compared with the control group,the serum levels of TC,TG,LDL-C,ox-LDL,ET-1,IL-6 and TNF-αincreased(P<0.01,P<0.05),HDL-C decreased(P<0.05)in the model group.The fat in AS region stained with oil red"O"was bright red,forming extensive and typical AS mature plaques.The intima thickened and plaque area increased with HE staining.TEM demonstrated decreased intracytoplasmic filaments,increased organelles such as rough endoplasmic reticulum and mitochondria,and more lipid droplets in the cytoplasm of VSMC,which showed typical synthetic changes.Compared with the model group,the serum levels of TC,TG,LDL-C,ox-LDL,ET-1 and IL-6 decreased in the statin group and the Danlou group(P<0.05,P<0.01),and the serum levels of HDL-C increased(P<0.05),TNF-αshowed a downward trend,but the difference was not statistically significant(P>0.05).The levels of TC,TG,oxLDL,

关 键 词：丹蒌片 血府逐瘀颗粒 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]