泻心汤及其有效成分组合物抗动脉粥样硬化作用的比较研究

Comparative study on anti-atherosclerosis effect of Xiexin decoction and its compositions of effective components

目的:在抗动脉粥样硬化(atherosclerosis, AS)主要药理作用环节比较泻心汤(XXD)与有效成分组合物(CECs)的效应,为阐明泻心汤抗AS效应物质基础提供依据。方法:选用转基因Fli1:eGFP品系斑马鱼幼鱼,通过喂食高胆固醇饲料10 d建立AS模型,实验分为空白组、模型组、阳性对照组(辛伐他汀,0.1μmol·L^(-1))、泻心汤组(50,250,500 mg·L^(-1))及有效成分组合物组(2.962、14.81、29.62 mg·L^(-1)),实验结束后,测定斑马鱼甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-c)、高密度脂蛋白胆固醇(HDL-c)、丙二醛(MDA)及超氧化物岐化酶(SOD)的含量,观察斑马鱼血管中胆固醇积累的情况。结果:与模型组比较,泻心汤及有效成分组合物能够明显降低斑马鱼TG、TC、LDL-c水平,提高HDL-c水平(P<0.05或P<0.01);降低MDA水平,提高SOD水平(P<0.05或P<0.01);抑制血管中胆固醇的积累(P<0.05或P<0.01),且有效成分组合物的效应强度可达到泻心汤的80%以上。结论:有效成分组合物在调节脂质水平、改善抗氧化能力及抑制血管中胆固醇积累等药理作用环节能较好的代表泻心汤发挥抗AS作用,可认为是泻心汤抗AS的主要效应物质。

OBJECTIVE To compare the effect of Xiexin decoction(XXD)with that of compositions of effective components(CECs)in main pharmacological processes against atherosclerosis(AS)and provide rationales for clarfying the anti-AS effective substance basis of XXD.METHODS Transgenic Fli1:eGFP zebrafish larvae was selected as an experimental object and AS zebrafish model established by feeding a high-cholesterol diet for 10 days.The zebrafishes were divided into nine groups of blank control, model, positive control(simvastatin, 0.1 μmol·L^(-1)),XXD(50/250/500 mg·L^(-1))and CECs(2.962/14.81/29.62 mg·L^(-1)).Upon the completion of experiment, the levels of triglyceride(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-c),high-density lipoprotein cholesterol(HDL-c),malondialdehyde(MDA)and superoxide dismutase(SOD)were determined.And the accumulation of cholesterol in zebrafish blood vessels was observed.RESULTS Compared with model group, XXD and CECs could significantly lower the levels of TG,TC,LDL-c, boost the level of HDL-c(P<0.05 or P<0.01);reduce the level of MDA and enhance the level of SOD(P<0.05 or P<0.01);suppress the accumulation of cholesterol in zebrafish blood vessels(P<0.05 or P<0.01).Also the efficacy of CECs could reach>80% of XXD.CONCLUSION CECs may achieve bioactive equivalence with XXD in main pharmacological processes against AS,including regulating lipid level, improving antioxidant activity and suppressing the accumulation of cholesterol in blood vessels.Thus CECs is a major anti-AS effective component of XXD.