小檗碱抑制胰岛素抵抗-高血压大鼠心室重构作用

目的观察小檗碱（berberine,Ber）和卡托普利（captopril,Cap）对高糖-高盐-高果糖诱导胰岛素抵抗-高血压（IRH）模型大鼠血压、血糖、胰岛素抵抗和心室重构作用。方法 Sprague-Dawley大鼠,雌雄各半,除空白对照组食用标准饲料外,其余动物随机喂饲富含高盐（4%）、高脂肪（25%）和高蔗糖（10%）饲料,并交替饮用5%蔗糖-1%食盐水与6%果糖水造模8周;当造模动物出现高血压、糖耐量减退,即建立IRH病理模型。然后将大鼠随机分为模型对照、卡托普利（Cap）25 mg/kg和Ber 300 mg/kg、150 mg/kg两个剂量组;分别灌胃给药或蒸馏水,每天1次共4周,测定大鼠血压及血清胰岛素（Fins）、血糖（FSG）,并计算胰岛素敏感指数（ISI）;计算心脏重量系数（CMI）和心肌增殖系数（MPI）以及作左心室组织学检测。结果 IRH大鼠血压升高,FPG和Fins含量增高,ISI减弱,MPI升高,与正常对照组比较,差异有显著性（P〈0.05或P〈0.01）,以及左心室组织呈心肌肥厚、重构和纤维化等病理改变。Ber 300 mg和150 mg/kg或Cap处理IRH大鼠后,降低IRH大鼠血压和FSG,纠正高胰岛素血症,增强ISI,差异有高度显著性（P〈0.01）;降低MPI（P〈0.01）,以及不同程度地改善左心室组织的病理改变。结论 Ber和Cap能对抗IRH大鼠胰岛素抵抗、增强胰岛素敏感性、纠正高胰岛素血症,降低血糖,降低血压,抑制心室重构。Ber上述效应呈量效关系。

The effects of berberine intervening insulin resistance, hypertension and ventricular remodeling in rats fed high salt-fat-sucrose- fructose-diet

Objective To investigate the effects of berberine（Ber） and captopril（Cap） on blood pressure,blood glucose,insulin resistance and ventricular remodeling in insulin resistant-hypertensive（IRH） rat fed high salt-fat-sucrose-fructose-diet. Methods Male and female for half and half Sprague-Dawley（SD） rats were randomized to receive feeding a high salt（4%）-fat（25%）-sucrose（10%）-enriched diet and alternately drinking 1% salt-5% sucrose water or 6% fructose water everyotherday,exception blank control fed standard rat chow and drinking distilled water,qd for 8 weeks,IRH rat model that the rats were exposed hypertension and impaired glucose tolerance（IGT） essentially established,and then the rats were randomly divided into model control group,Cap group 25 mg/kg,and Ber 300 mg/kg,150 mg/kg,solvent or the drugs were adiministered by intragastric administration（ig） qd for 4 weeks.The systolic pressure（SP）,the levels of fasting serum glucose（FSG） and fasting insulin（Fins） were be measured as well as insulin sensitivity index（ISI）,cardiac mass index（CMI）,myocardial proliferation index（MPI） were be counted,the histopathology in left ventricle was observed after experiment. Results In IRH rats,the SP were raised,the concentrations of FSG and Fins were increased,ISI weakened,MPI was raised compared with the blank control rats（P〈0.05 or P〈0.01）,as well as a series of histopathologic variety in left ventricle such as myocardial hypertrophy,ventricular remodeling and fibrosis were appeared.All above data in the IRH rats treated by Cap and Ber 300 mg/kg,150 mg/kg,SP were decreased（P〈0.01）,FSG lowered（P〈0.01）,hyperinsulinemia moderated（P〈0.01）,ISI strengthened（P〈0.01）.MPI reduced（P〈0.01）,histopathologic variety in left ventricle ameliorated. Conclusion Ber and Cap are able to antagonist insulin resistance,enhance the insulin sensitivity,modify hyperinsulinemia,reduce blood glucose and depress blood pressure,inhibit or suspend ventricular remodeling in IRH rats.The effects of berberine show dose-effect relationships.