代谢综合征大鼠胰岛素敏感性低下高血压和氧化应激及卡托普利干预作用

The effects of captopril on insulin sensitivity,hypertension and oxidative stress in rat model of metabolic syndromie fed high salt-fat-sucrose-diet

目的观察卡托普利(Cap)对代谢综合征(MetS)大鼠胰岛素敏感性及血压、肾素-血管紧张系统、一氧化氮(NO)及其合成、血糖和血脂以及氧化应激作用。方法Sprague-Dawley大鼠,雌雄各半,建立MetS大鼠模型;将病鼠随机分为模型对照、模型Cap 7mg/kg;3组大鼠分别肌肉注射消毒溶媒或药物,每日1次×4周;测定大鼠血压、空腹血糖(FBG)和口服糖耐量试验2h血糖(OGTT-2hBG)及血浆空腹胰岛素(FIns),血浆血糖含量(FPG),并计算胰岛素敏感指数(ISI),测血清甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、NO、肿瘤坏死因子(TNF)-α、肾素和血管紧张素含量和一氧化氮合酶(NOS)、诱导型NOS(iNOS)和超氧化物岐化酶(SOD)活性。结果与正常对照组比较,MetS大鼠血压升高、FBG和OGTT-2 hBG、FPG和FIns含量增高,ISI减弱,血清TG、TC、TNF-α和肾素、血管紧张素含量增高(P<0.05)。经Cap处理MetS大鼠后,血压降低(P<0.01),FPG,FBG,OGTT-2hBG降低和IGT改善(P<0.05),纠正高胰岛素血症(P<0.05),增强ISI(P<0.05),降低TG、TC、NO和丙二醛(MDA)含量,抑制NOS和iNOS活性,提高SOD活性(P<0.05),下调血管紧张素和TNF-α含量(P<0.05);但比较LDL-C,HDL-C和肾素含量,差异无统计学意义(P>0.05)。结论Cap对抗MetS大鼠胰岛素抵抗、增强胰岛素敏感性、纠正高胰岛素血症,降低血压、血糖和血脂,拮抗肾素、血管紧张素Ⅱ转换以及增强抗氧化作用。

Objective To investigate the effects and effective mechanisms of captopril on decreasing blood pressure, improving insulin sensitivity, lowering blood glucose, reducing blood lipid and inhibiting oxidative stress in metabolic syndromic （MetS） rat model fed with high salt-fat-sucrose-diet. Methods Male and female for half and half Sprague-Dawley （SD） rats were used to establish Mets rat model; and then the rats were randomly divided into model control group, captopril group 7 mg/kg, except normal group fed standard rat chow; sterilized solvent or the drugs intramuscularly injected qd for 4 weeks. The blood pressure （BP） , fasting plasma glucose（FPG） and fasting insulin （Fins） as well as insulin sensitivity index （ISI） were measured; fasting blood glucose （FBG）, 2-hours blood glucose （2hBG） after oral glucose tolerance test（OGTT）, the contents of triglyceride （TG）, total cholesterol （TC）, low- or high-density lipoprotein-cholesterol （LDL-C or HDL-C）, rennin, angiotensin, tumor necrosis factor （TNF）-α, nitric oxide（NO）, malondialdehyde （MDA）, and the activities of nitric oxide synthase（NOS）, inducible nitric oxide synthase （iNOS）, superoxide dismutase（SOD） were determined after treatment. Results In MetS rats, the BP were elevated, FBG and OGTT- 2hBG, FPG and Fins were increased, ISI weakened, the concentrations of TG, TC, rennin, angiotensin, TNF-α were increased compared with the normal control rats （P〈0.05-0.01）. BP were decrease （P〈0.01）, FPG, FBG, OGTT-2hBG lowered and 1GT improved （P〈0.05-0.01）, hyperinsulinemia moderated （P〈0.05-0.01）, ISI strengthened （P〈0.01） , contents of TG, TC ,NO, MDA and the activities of NOS, iNOS reduced （P〈0.05- -0.01）, activity of SOD promoted （P〈0.05） concentrations of angiotensin and TNF-α downregulated （P〈0.05-0.01）, the data above mentioned in the MetS rats treated by captopril were significant difference; whereas the concentrations of rennin, LDL-C and HDL-C were not significant （P〉0.05）. Conclusion Captopril appeared to suppress insulin resistance, enhance the insulin sensitivity, modify hyperinsulinemia, depress blood pressure, adjust metabolic dysfunction of blood glucose aM lipids, and antagonize rennin converted to angiotensin Ⅱ, increase antioxidation in MetS rats.