白藜芦醇对高血脂模型小鼠的预防作用和对模型金黄地鼠的改善作用研究

摘要

OBJECTIVE:To study the preventive effect of resveratrol on model mice and improvement effect on model golden hamsters (shorter for hamsters) with hyperlipidemia. METHODS:Hyperlipidemia animal models were induced by using high-fat and high-cholesterol diet. Mice and hamsters were both randomly divided into model group and resveratrol low-dose, medi-um-dose,high-dose groups(40,80,160 mg/kg for mice,25,50,100 mg/kg for hamsters),10 in each group. 10 corresponding animals were selected as normal control group. Except that normal control group was fed normal diet and intragastrically administrat-ed normal saline,other mice were intragastrically administrated relevant medicines when fed high-fat and high-cholesterol diet;oth-er hamsters were firstly modeled for 2 weeks and intragastrically administrated relevant medicines after modeling. High-fat and high-cholesterol diet was fed during administration. It was administrated for 4 weeks. Total cholesterol(TC)and low density lipo-protein cholesterol(LDL-C)levels in serum of mice and hamsters were detected every week. After 4 weeks,pre-protein converting enzyme subtilisin 9(PCSK9)mRNA and protein expression,microRNA-27a(miRNA-27a)expression in serum of mice and ham-sters,and low density lipoprotein receptor(LDLR)protein expression in liver tissue of mice were detected. RESULTS:Compared with normal control group,the TC,LDL-C,PCSK9 mRNA and protein,miRNA-27a levels of mice in model group were obvious-ly increased after 2 weeks of administration (P<0.05);LDLR protein level in liver tissue was obviously decreased (P<0.05). TC,LDL-C,PCSK9 mRNA and protein,miRNA-27a levels of hamsters in model group were obviously increased (P<0.05). Compared with model group,above-mentioned indexes of mice and hamsters in each administration group were obviously im-proved(P<0.05),which were positively correlated with dose. CONCLUSIONS:Resveratrol has preventive effect on model mice and improvement effect on model golden hamsters with hyperlipidemia. The mechanism may be down-regulating miRNA-27a ex-pression and PCSK9 protein expression in serum,to increase LDLR protein level in liver tissue,and finally reduce LDL-C level.%目的:研究白藜芦醇对高血脂模型小鼠的预防作用和对模型金黄地鼠(以下简称地鼠)的改善作用.方法:以高脂高胆固醇饲料饲养诱导高血脂动物模型.将小鼠和地鼠均分为模型组和白藜芦醇低、中、高剂量组(小鼠给予40、80、160 mg/kg,地鼠给予25、50、100 mg/kg),每组10只,同时设立10只相应动物为正常对照组.除正常对照组动物喂食正常饲料和ig生理盐水外,其余小鼠在喂食高脂高胆固醇饲料的同时ig相应药物;其余地鼠先建模2周,成模后再ig相应药物,给药期间继续喂食高脂高胆固醇饲料.持续给药4周,每周检测各组小鼠和地鼠血清中总胆固醇(TC)和低密度脂蛋白胆固醇(LDL-C)水平,给药4周后检测各组小鼠和地鼠血清中前蛋白转化酶枯草溶菌素9(PCSK9)mRNA及蛋白、微小RNA-27a(miRNA-27a)表达,以及小鼠肝组织中低密度脂蛋白受体(LDLR)蛋白表达.结果:与正常对照组比较,模型组小鼠从给药2周后开始血清中TC、LDL-C、PCSK9 mRNA及蛋白、miRNA-27a水平均明显升高(P<0.05),肝组织中LDLR蛋白水平明显降低(P<0.05);模型组地鼠给药期间血清中TC、LDL-C、PCSK9 mRNA及蛋白、miRNA-27a水平均明显升高(P<0.05).与模型组比较,各给药组小鼠和地鼠上述指标均明显改善(P<0.05),且与剂量呈正相关.结论:白藜芦醇对高血脂模型小鼠有预防作用,对模型地鼠有改善作用.其机制可能是通过下调血清中miRNA-27a表达与PCSK9蛋白表达,进而升高肝组织中LDLR蛋白水平,最终降低血清中LDL-C水平.