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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 a rabbit model of atherosclerosis and to study the effect of dancao tablet on the expression of BIP in rabbits with atherosclerotic lesions and endoplasmic reticulum stress (ERS) The application of experimental basis. Methods: Twenty-four male Japanese white rabbits were randomly divided into normal group, model group, fixed group and fixed + Dan Dan tablet combination group, 6 in each group. The normal group fed normal feed, the model group in the general feed by adding 2% cholesterol and 0.02% methionine; can be fixed group, can be set + Dan Jian tablet group in the general feed with 2% cholesterol and 0.02% methionine and the corresponding control drug , Copy the model of atherosclerosis in rabbits. The levels of cholesterol, triglyceride, LDL-C, HDL-C and apolipoprotein A (Apo A) and apolipoprotein B (Apo B). After 9 weeks of feeding, the upper thoracic aorta and the hematoxylin and eosin (HE) were stained to observe the histological changes. The expression of BIP gene was detected by in situ hybridization. Results: Compared with the normal group, the levels of TC, TG, LDL-C and Apo B in the model group were significantly increased, while the levels of HDL-C and Apo A in the model group were significantly decreased (P <0.05) Tanshin tablet combined treatment group significantly reduced blood lipids TC, TG, LDL-C, Apo B levels, significantly increased HDL-C, Apo A content (P <0.01). The normal intima of HE staining was in normal morphology. Intimal hyperplasia and endothelial cell injury were observed in model group. Mild hyperplasia of vascular intima was found in the model group. In situ hybridization results showed that the expression of BIP protein in the model group was significantly increased; the expression of BIP protein was down-regulated in the model group and in the Dan Dan tablet group. Conclusion: The combination of danji tablet can delay the development of atherosclerosis, and the effect is remarkable.