氯苯氧异丁酸甲氧基苯丙烯酸酯衍生物对高脂血症模型大鼠的降血脂及抗氧化作用研究

Lipid-lowering and Anti-oxidation Effects of(E)-3-[4-[2-(4-chlorophenoxy)-2-methylpropanoyloxy]-3-methoxyphenyl] Acrylic Acid Derivatives on Hyperlipidemia Model Rats

目的:研究氯苯氧异丁酸甲氧基苯丙烯酸酯(AZ)衍生物对高脂血症模型大鼠的降血脂及抗氧化作用。方法:取10只大鼠作为空白对照组,另80只大鼠建立高脂血症模型后随机均分为模型组、AZ(83 mg/kg)组、AZ甲醇酯(86.3 mg/kg)组、AZ乙醇酯(89.3 mg/kg)组、AZ苯酚酯(99.5 mg/kg)组、AZ对氯苯酚酯(106.8 mg/kg)组、AZ对甲基苯酚酯(102.5 mg/kg)组和阳性对照(非诺贝特100 mg/kg)组。除空白对照组和模型组大鼠灌胃0.5%羧甲基纤维素钠生理氯化钠溶液外其余各组大鼠给予相应药物,每日1次,连续2周,每周称体质量2次。末次给药后禁食12 h静脉取血,测定血清中总胆固醇(TC)、高脂血症(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)水平和超氧化物歧化酶(SOD)、丙二醛(MDA)、过氧化氢酶(CAT)活性。结果:与空白对照组比较,其他各组大鼠的体质量差异无统计学意义(P>0.05);模型组大鼠血清中TC、TG、LDL-C、MDA水平均明显增加(P<0.05或P<0.01),HDL-C、SOD、CAT水平明显降低(P<0.01)。与模型组比较,AZ组及其衍生物组大鼠血清中TC、TG、LDL-C、MDA水平均明显降低(P<0.05或P<0.01),SOD、CAT水平明显升高(P<0.01),HDL-C水平仅阳性对照组明显增加(P<0.01)。结论:AZ及其衍生物对高脂血症模型大鼠有一定的降血脂和抗氧化作用。

OBJECTIVE：To investigate the lipid-lowering and anti-oxidation effects of chlorophenoxyacetic isobutyrate methoxy acrylate {（E）-3-[4-[2-（4-chlorophenoxy）-2-methylpropanoyloxy]-3-methoxyphenyl] acrylic acid,AZ} derivatives on hyperlipidemia model rats. METHODS：10 rats were included into blank control group,and other 80 hyperlipidemia model rats were induced and randomly divided into model group,AZ（83 mg/kg）group,AZ methanol acetate（86.3 mg/kg）group,AZ ethanol ester（89.3 mg/kg）group,AZ phenol（99.5 mg/kg）group,AZ chlorophenol ester（106.8 mg/kg）group,AZ methyl phenol ester（102.5mg/kg）group and positive control（fenofibrate 100 mg/kg）group. Except blank control group and model group were given 0.5%Sodium tvlose sodium chloride physiological solution intragastrically,other groups were given relevant medicine once a day for consecutive 2 weeks. Body weights of rats were weighed twice a week,and blood samples were collected from vein after fasting for12 h following last administration. The serum levels of TC,TG,LDL-C and HDL-C,and the activities of SOD,MDA and CAT were determined. RESULTS：Compared with blank control group,body weight of rats had no statistically significant difference（P〉0.05）;the serum levels of TC,TG,LDL-C and MDA were increased significantly in model rats（P〈0.05 or P〈0.01）,while the serum levels of HDL-C,SOD and CAT were decreased significantly（P〈0.01）. Compared with model group,the serum levels of TC,TG,LDL-C and MDA were decreased significantly in AZ group and other derivatives group（P〈0.05 or P〈0.01）,while the serum levels of SOD and CAT were increased significantly（P〈0.01）;the level of HDL-C was increased significantly in positive control group（P〈0.01）. CONCLUSIONS：AZ and its derivatives have certain lipid-lowering and anti-oxidation effect in hyperlipidemic model rats.