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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 observe the effect of berberine and captopril on insulin-induced metabolic syndrome (MetS-H) -induced ventricular remodeling in rats with hyperlipidemia-high salt-high fructose Insulin resistance (IR), blood pressure, glucose, glycosylation products and oxidative stress and inflammatory cytokines. METHODS: Sprague-Dawley rats were fed a diet rich in salt (4%), high fat (25%) and high sucrose (10%) with the exception of standard diet and drinking distilled water. Alternate consumption of 5% sucrose -1% saline and 6% fructose water modeling for 8 weeks; when the model animals appear high blood pressure, impaired glucose tolerance, the establishment of MetS-H pathological model. The rats were then randomly divided into two groups: model control, captopril 25mg / kg and berberine 300mg / kg and 150mg / kg. The rats were intragastrically administrated with distilled water or qd for 4 weeks, and the blood pressure and serum insulin (Fins) FSG, GSP, MDA, NO, AngⅡ, TNF-α (TNF-α ), The content of TGF-β1 and the activities of nitric oxide synthase (NOS), inducible nitric oxide synthase (iNOS), superoxide dismutase (SOD), cardiac ATPase, Insulin sensitivity index (ISI) was calculated. Pathological changes of left ventricular myocardium and blood vessels were observed under light microscope. Results: The blood pressure of MetS-H rats increased, the content of FSG and Fins increased, the ISI decreased, the levels of AngⅡ, serum TNF-α and TGF-β1 increased significantly, the activity of NOS increased obviously and the content of GSP, GHb, MDA and NO significantly increased Elevated serum SOD activity was significantly lower (P <0.01 or P <0.05). MetS-H rats were treated with berberine 300mg / kg and 150mg / kg and captopril 25mg / kg, respectively, to reduce the content of blood pressure and the contents of FSG, GHb, AngⅡ, TNF-α, (P <0.05 or P <0.01). However, only berberine 300 mg / kg decreased the level of GSP (P <0.01). CONCLUSION: Berberine and captopril antagonize IR of MetS-H rats, enhance insulin sensitivity, inhibit glycosylation-oxidative stress, down-regulate inflammatory cytokines, decrease blood pressure, and improve pathological changes of left ventricular tissues and blood vessels to varying degrees , berberine above effect was dose-effect relationship.