染料木素对大鼠食饵性高脂血症PON1及CRP的影响

目的探讨染料木素(genistein,Gen)对大鼠食饵性高脂血症对氧磷酶(paraoxonase,PON1)活性及C-反应蛋白(C-reactive protein,CRP)的影响。方法健康SD大鼠40只,♀♂各半,随机分为以下5组:①普食组;②高脂血症模型组;③低剂量Gen(0.5 mg.kg-1.d-1)组;④高剂量Gen(5 mg.kg-1.d-1)组;⑤辛伐他汀(5 mg.kg-1.d-1)阳性药物对照组;除普食组给以普通饲料喂养外,其他组均饲以高脂饲料喂养加敌百虫(10 mg.kg-1.d-1)腹腔注射,建立食饵性高脂血症模型。各组大鼠连续喂养及同时用药8周,每2周测1次体重,根据体重调整用药量;定期取血检测胆碱酯酶(acetylcholine esterase,AChE)、血脂、丙二醛(ma-lonaldehyde,MDA)、PON1和CRP的含量,用苏木精/伊红(hematoxylin/eosin,HE)染色检测大鼠肝脏及主动脉弓病理形态变化。结果与模型组相比,高剂量Gen组与辛伐他汀组大鼠总胆固醇(total cholesterol,TC)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)及动脉粥样硬化指数(atherosclerotic index,AI)明显降低,高密度脂蛋白胆固醇(high density lipoprotein cholesterol/total cholesterol,HDL-C)与TC比值(HDL-C/TC)明显升高,血清MDA含量也明显降低,同时还能明显降低高脂饲料喂养加低剂量敌百虫腹腔注射致高脂血症大鼠血清CRP含量,提高PON1活性,改善大鼠肝与主动脉弓形态变化。结论Gen可以减轻高脂饲料喂养加敌百虫诱发的大鼠高脂血症;其作用机制可能与逆转血脂障碍,抑制过氧化脂质作用抗氧化,降低炎症因子CRP抗炎及通过PON1酶的调节有关。

Effect of genistein on paraoxonase and C-reactive protein of the rats with food-induced hyperlipidemia

Aim To investigate the effect of genistein on paraoxonase(PON1) activity and inflammatory factor C-reactive protein(CRP) of the hyperlipidemic rats induced by high-lipid food.Methods Healthy Sprague-Dawley rats,twenty male and twenty female,were randomly divided into five groups:control group,hyperlipidemic model group,low-dose genisein(0.5 mg·kg-1 per day) group,high-dose genisein(5 mg·kg-1 per day) group and simvastatin group.All groups were fed with high fat food and intraperitoneally injected trichlorfon(10 mg·kg-1·day-1,ip) except for the control group,setting up the food-induced hyperlipidemic model.The drug dose was adjusted according to the body weight of each rat measured every other week and the drug administration lasted for eight weeks consecutively.The contents of the cholinesterase,the blood lipid,malonaldehyde,PON1 and CRP were measured on regular blood testing.Hematoxylin/eosin(HE) staining was used to test the pathological changes within the rat liver and aortic arch.Results Compared to the hyperlipidemic model group,the levels of TC,LDL-C and AI decreased significantly in the simvastatin group and the high-dose genistein group,while the HDL-C/TC increased significantly in this two groups.The level of MDA as well as that of CRP was reduced significantly,while the PON1 activity was enhanced and the morphological changes of the liver and the aortic arch were improved in the rats that were treated with the intraperitoneal trichlorfon injection and the high-lipid food.Conclusions Genistein can suppress the development of hyperlipidemia induced by high-lipid food and the intraperitoneal trichlorfon injection.The mechanism may relate to the reversion of dyslipidemia,the inhibition of lipid peroxidation,the lowering effect on the CRP,and the regulation of PON1 system.