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小檗碱抑制胰岛素抵抗-高血压大鼠心室重构作用
The effects of berberine intervening insulin resistance,hypertension and ventricular remodeling in rats fed high salt-fat-sucrose-fructose-diet
【Author】 FENG Rui-er1,LIN Jia 2,Lü Jun-hua3,LI Bo-ping2,PAN Jing-qiang4 (1 Advanced Medical Service Center,The Second Affilliated Hospital of Guangzhou Medical College,Guangzhou 510260,China; 2 Dep of Pharmacy,Guangzhou Hospital Traditional Chinese medicine,Guangzhou 510130,China; 3 Dep of pharmacology,College of Pharmacy in Jinan University,Guangzhou 510632,China; 4 Dept. of Pharmacology,Guangzhou Institute of Traditional Chinese Medicine & Materia Medica,Guangzhou,510130,China.)
【机构】 广州医学院第二附属医院高级医疗服务中心; 广州市中医医院药剂科; 暨南大学药学院药理教研室; 广州市中医中药研究所药理研究室;
【摘要】 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,♀♂各半,除空白对照组食用标准饲料和饮用蒸馏水外,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、Cap25mg·kg-1和Ber300mg·kg-1,150mg·kg-1两个剂量组;分别灌胃给药或蒸馏水,qd×4w,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。Ber300mg和150mg·kg-1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以上效应呈量效关系。
【Abstract】 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 25mg·kg-1, and Ber 300mg·kg-1, 150mg·kg-1; 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 300mg·kg-1, 150mg·kg-1, 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. Conclusions 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.
【Key words】 berberine; captopril; insulin resistance; hypertension; rats; ventricular remodeling;
- 【会议录名称】 2010年中国药学大会暨第十届中国药师周论文集
- 【会议名称】2010年中国药学大会暨第十届中国药师周
- 【会议时间】2010-11
- 【会议地点】中国天津
- 【分类号】R285.5
- 【主办单位】中国药学会(Chinese Pharmaceutical Association)、天津市人民政府