气血并治方组分配伍防治兔动脉粥样硬化的实验研究

Study of Component Compatibility from Qixue Bingzhi Recipe in Preventing and Treating Rabbit Arteriosclerosis

目的从脂质代谢、血管内皮功能、炎症介质水平和斑块稳定性等方面探讨气血并治方组分配伍防治免疫损伤结合高脂饲料致兔实验性动脉粥样硬化(AS)模型的药理效应和作用机制。方法日本大耳白兔70只,雄性,经耳缘静脉注射牛血清白蛋白生理盐水溶液(250 mg·kg-1)造成免疫应激损伤,注射后即喂食高脂饲料复制AS模型,气血并治方组分配伍分为A、B、C、D、E、F共6个部位。实验分为1正常对照组(普通颗粒饲料);2模型组(高脂颗粒饲料,以下各组相同);3阳性对照药组,辛伐他汀3.60 mg·kg-1;4全方提取物配伍组,气血并治方1.11 g·kg-1;5D+E配伍组,0.247 g·kg-1;6D+E优化组,0.247 g·kg-1;7D+E原方配伍+F部位提取物组(D+E+F配伍组),0.26 g·kg-1。所试药物用自来水稀释所需浓度,连续灌胃72 d,实验结束后测定兔主动脉斑块病理、血脂水平、血浆内皮素(ET)和降钙素基因相关肽(CGRP)含量、白介素-6(IL-6)和白介素-8(IL-8)水平等指标。结果病理图像分析表明,全方提取物组、D+E+F配伍组、辛伐他汀组与模型组的斑块管腔面积比较,差异有统计学意义(P<0.01),各给药组的兔主动脉斑块积分值均较模型组显著降低(P<0.01,P<0.05)。与模型组比较,D+E配伍组、D+E优化组、D+E+F配伍组能显著降低甘油三酯(TC)、低密度脂蛋白(LDL-C)和载脂蛋白(Apo B)的水平(P<0.05,P<0.01);全方提取物组、D+E配伍组、D+E优化组及D+E+F配伍组均有降低ET和升高一氧化氮(NO)的作用(P<0.05,P<0.01),全方提取物组、D+E+F配伍组可显著降低IL-6水平(P<0.05,P<0.01)。结论气血并治方全方提取物和D+E+F配伍对兔AS的诸多环节均有一定的药理作用,不同提取物配伍对防治AS的环节不尽相同,综合效果,气血并治全方提取物组和D+E+F配伍组具有一定的优势。

Objective To evaluate the pharmacological effect and mechanism of Qixue Bingzhi Recipe（QBR）effective constituents for preventing and treating rabbit arteriosclerosis（AS）induced by immune injury combined with high-fat forage through observing the related indexes of lipid metabolism,vascular endothelial function,inflammatory mediator and plaque vulnerability. Methods Seventy Japanese male white rabbits were used in the study. After intravenous injection of bovine serum albumin（250 mg·kg^-1） through auricular vein,the rabbits were given high fat feeding to establish AS model. The QBR effective constituents were divided to six parts,A,B,C,D,E and F. The rabbits were divided into 7 group,normal control group,hyperlipidemia model group,positive control group（simvastatin 3.60mg·kg^-1）,QBR extract group（QBR 1.11 g·kg^-1）,QBR effective constituent D,E combination group（0.25 g·kg^-1）,QBR effective constituent D,E optimized combination group（0.25 g·kg^-1）,and QBR effective constituent D,E and F combination group（0.26 g·kg^-1）. The normal control group was fed with ordinary forage and was given gastric perfusion of normal saline, and the other groups were fed with high fat forage and treated with gastric perfusion according to drug compatibility proportion for 72 continuous days. At the end of the experiment, the rabbits were sacrificed to observe the pathology of aortic plaques, and to measure the levels of blood lipid, plasma endothelin（ET）,calcitonin gene-related peptide（CGRP）,interleukin-6（IL-6）and interleukin-8（IL-8）. Results Pathological image analysis showed that aortic plaque area and plaque value in simvastatin group,QBR extract group,and QBR effective constituent D,E and F combination group were decreased（P〈0.01 or P〈0.05 compared with the model group）. After treatment,triglyceride（TC）,low-density lipoprotein cholesterol（LDL-C）and apolipoprotein B（Apo B）were decreased in QBR effective constituent D, E combination group, QBR effective constituent D, E optimized combination group,and QBR effective constituent D,E and F combination group（P〈0.01 or P〈0.05 compared with the model group）. Compared with the model group,ET was decreased and NO was increased in QBR extract group, QBR effective constituent D, E combination group, and QBR effective constituent D, E optimized combination group（P〈0.05, P〈0.01）, and IL-6 was decreased in QBR extract group, and QBR effective constituent D, E and F combination group（P〈0.01）. Conclusion The QBR effective constituents compatibility shows pharmacological action on rabbit AS at different levels,and QBR extract and QBR part D,E and F combination have obvious comprehensive pharmacological action for rabbit AS.