摘要
目的:观察小檗碱(berberine)和卡托普利(captopril)对高脂-高盐-高果糖诱导代谢综合征(metabolic symptom,MetS)-高血压(MetS-H)心室重构大鼠胰岛素抵抗(insulin resistance,IR)、血压、血糖、糖基化产物和氧化应激及炎性细胞因子的影响。方法:Sprague-Dawley大鼠,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MetS-H病理模型。然后将大鼠随机分为模型对照、captopril 25mg/kg以及berberine 300mg/kg和150mg/kg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)、糖化血清蛋白(GSP)、糖化血红蛋白(GHb)、丙二醛(MDA)、一氧化氮(NO)、血管紧张素Ⅱ(AngⅡ)、肿瘤坏死因子-α(TNF-α)、转化生长因子-β1(TGF-β1)的含量和一氧化氮合酶(NOS)、诱导型一氧化氮合酶(iNOS)、超氧化物歧化酶(SOD),心脏ATP酶的活性,并计算胰岛素敏感指数(ISI);光学显微镜下观察左心室心肌组织及血管的病理学改变。结果:MetS-H大鼠血压升高,FSG和Fins含量升高,ISI减弱,AngⅡ、血清TNF-α、TGF-β1明显升高,NOS活性明显升高、GSP、GHb、MDA和NO含量明显升高、血清SOD活性显著降低(P<0.01或P<0.05)。berberine 300mg/kg和150mg/kg以及captopril 25mg/kg处理MetS-H大鼠后,降低MetS-H大鼠血压和FSG、GHb、AngⅡ、TNF-α、TGF-β1、MDA、NO含量及NOS、ATP酶活性,纠正高胰岛素血症,增强ISI,提高SOD活性,差异有显著性(P<0.05或P<0.01),但只有berberine 300mg/kg降低GSP含量(P<0.01)。结论:berberine和captopril对抗MetS-H大鼠IR、增强胰岛素敏感性,抑制糖基化-氧化应激反应,下调炎性细胞因子、降低血压,以及不同程度地改善左心室组织和血管的病理改变,berberine以上效应呈量效关系。
Objective：To investigate the effect of berberine（Ber） on insulin resistance,blood pressure,glycation-oxidative stress and inflammatory cytokines in metabolic syndrome and hypertensive（MetS-H） rat models with ventricular remodeling.Methods：Male and female for half and half Sprague-Dawley（SD） rats exception blank control fed standard rat chow and drinking distilled water qd for 8 weeks,and the others were received feeding a high salt（4%）-fat（25%）-sucrose（10%）-enriched diet and alternately drinking 1% salt-5% sucrose water or 6% fructose water everyotherday,qd for 8 weeks,MetS-H rat model was essentially established.And then the rats were randomly divided into model control group,Cap group 25mg/kg,Ber 300mg/kg and 150mg/kg.Solvent or the drugs were adiministered by intragastric administration（ig） qd for 4 weeks.After 12 weeks the systolic pressure（SP）,levels of fasting insulin（Fins）,fasting serum glucose（FSG）,glycosylated serum protein（GSP）,glycosylated hemoglobin（GHb）,malondialdehyde（MDA）,nitric oxide（NO）,angiotensin（Ang）Ⅱ,tumor necrosis factor（TNF）-α,transforming growth factor（TGF）-β1 were be measured;and activities of superoxide dismutase（SOD）,nitricoxide synthase（NOS） were be determinated;as well as insulin sensitivity index（ISI） was be counted,pathology changes on the left ventricle cardiac muscle organization and blood vessel were observed under the optical microscope.Results：Compared with the blank control rats,the SP and the components of AngⅡ,TNF-α,TGF-β1 were increased obviously,the concentrations of Fins,FSG,MDA,NO,GSP and GHb were increased,NOS were increased but SOD was decreased significantly,ISI was weakened in MetS-H rats（P0.05 or P0.01）;MetS-H rats treated by Cap25mg/kg,Ber 300mg/kg and 150mg/kg,SP was lowered（P0.01）,levels of FSG,GHb,AngⅡ,TNF-α,TGF-β1,MDA,NO and activity of NOS were reduced（P0.01）,hyperinsulinemia was moderated（P0.01）,ISI was strengthened（P0.01）,activity of SOD were increased（P0.01）,but content of the GSP was curbed by Ber 300mg/kg only（P0.01）.Conclusion ：The results suggest that Ber and Cap can antagonist insulin resistance,enhance the insulin sensitivity,modify hyperglycemia,inhibit glycation-oxidative stress,down-regulate inflammatory cytokines,depress blood pressure in MetS-H rats,which are some parts of pharmaceutical mechanism for intervening metabolic syndrome,hypertension and ventricular remodeling.The effects of berberine show dose-effect relationships.
出处
《中药药理与临床》
CAS
CSCD
北大核心
2011年第6期13-17,共5页
Pharmacology and Clinics of Chinese Materia Medica
基金
广东省社会发展领域科技计划项目(№:73111)
广东省中医药局项目(№:2040047)
广州市中医药
中西医结合项目(№:2004A027)基金资助
关键词
小檗碱
代谢综合征
高血压
心室重构
糖氧化应激反应
炎性细胞因子
berberine
metabolic syndrome
hypertension
ventricular remodeling
glycoxidative stress
inflammatory cytokines
