摘要
目的:建立兔动脉粥样硬化模型,研究丹蒌片对兔粥样硬化病变及内质网应激(ERS)相关基因免疫球蛋白重链结合蛋白(BIP)表达的影响,为丹蒌片临床的应用提供实验依据。方法:雄性日本大耳白兔24只随机分为正常组、模型组、可定组和可定+丹蒌片联合用药组,每组6只。正常组饲喂普通饲料,模型组在普通饲料中加入2%胆固醇及0.02%蛋氨酸;可定组、可定+丹蒌片组在普通饲料中加入2%胆固醇及0.02%蛋氨酸及相应的对照药物,复制家兔动脉粥样硬化病变模型。分别在用药前与饲养9周后检测胆固醇(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)值,载脂蛋白A(Apo A),载脂蛋白B(Apo B);饲养9周后取实验动物胸主动脉上段,苏木素-伊红(HE)常规染色后观察组织形态变化;应用原位杂交技术检测BIP基因表达。结果:与正常组比较,模型组兔血脂TC,TG,LDL-C,Apo B含量明显升高,HDL-C,Apo A含量明显降低(P<0.05);与模型组比较,可定组、丹蒌片联合用药组明显降低兔血脂TC,TG,LDL-C,Apo B含量,明显升高HDL-C,Apo A含量(P<0.01)。HE染色正常组血管内膜形态正常;模型组内膜严重增生,内皮细胞损伤;可定组血管内膜轻度增生;可定+丹蒌片组血管内膜形态接近正常。原位杂交结果显示,模型组BIP蛋白的表达明显升高;可定组及可定+丹蒌片组可下调BIP蛋白的表达。结论:丹蒌片联合可定能延缓动脉粥样硬化的发展,且效果显著。
Objective： To establish atherosclerosis rabbit models,study the effect of Danlou tablet on atherosclerosis and the expression of endoplasmic reticulum stress（ ERS） related genes immunoglobulin heavy chain binding protein（ BIP）,and provide experimental basis for clinical application of Danlou tablet. Method：The 24 male big-eared Japanese rabbits were randomly divided into normal group,model group,Rosuvastatin group,Danlou tablet ＋ Rosuvastatin group,with 6 rabbits in each group. Normal group was fed with standard diet,while in model group,2% cholesterol and 0. 02% methionine were added in standard diet. In Rosuvastatin group and Danlou tablet ＋ Rosuvastatin group,2% cholesterol,0. 02% methionine and the corresponding control drug were added in the standard diet to establish atherosclerosis rabbit models. Before medication and after 9 weeks of treatment,cholesterol（ TC）,triglyceride（ TG）,low density lipoprotein cholesterol（ LDL-C）,high density lipoprotein cholesterol（ HDL-C）,apolipoprotein A（ Apo A） and apolipoprotein B（ Apo B） values were detected.After 9 weeks of treatment,thoracic aorta segment was taken from the experiment animals to observe morphological changes by HE. In situ hybridization was used to detect BIP gene expression. Result： Compared with the normal group,TC,TG,LDL-C and Apo B levels in model group were significantly higher,while HDL-C and Apo A levels were significantly lower（ P〈 0. 05）. Compared with the model group,TC,TG,LDL-C and Apo B levels in Rosuvastatin group and Danlou tablet ＋ Rosuvastatin group were significantly lower,while HDL-C and Apo A levels were significantly higher（ P 〈0. 01）. HE staining showed normal endangium morphology in normal group,severe hyperplasia of endometrium and endothelial cell damages in model group,mild hyperplasia of endometrium in Rosuvastatin group,and close to normal endangium morphology in Danlou tablet ＋ Rosuvastatin group. In situ hybridization results showed that BIP protein expression was significantly increased in model group, and Rosuvastatin group and Danlou tablet ＋ Rosuvastatin group could down-regulate BIP protein expressions.Conclusion： Danlou tablet combined with Rosuvastatin can delay the development of atherosclerosis and have significant therapeutic effect.
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2015年第23期126-129,共4页
Chinese Journal of Experimental Traditional Medical Formulae
基金
河南省基础与前沿技术研究计划项目(112300410156)
郑州市科技创新团队项目(121PCXTD520)
河南省高等学校青年骨干教师计划项目(2013GGJS-093)
关键词
丹蒌片
动脉粥样硬化
内质网应激
免疫球蛋白重链结合蛋白
Danlou tablet
atherosclerosis
endoplasmic reticulum stress
immunoglobulin beavy chains binding protein
