白芍总苷对代谢综合征-高血压大鼠改善胰岛素敏感性、降压和抗氧化作用

Effects of total glucosides of paeong on improving insulin sensitivity,lowering blood pressure and enhancing antioxidation in metabolic syndrome-hypertensive rats

目的:探讨白芍总苷(TGP)对代谢综合征-高血压(metabolic syndromic-hypertension,MS-Ht)大鼠血压的作用,检测胰岛素敏感性、细胞因子、血管活性物质以及氧化应激的改变,研究其作用机制。方法:采用高脂、高糖饮食喂饲SD大鼠,连续8周,当造模动物出现高血压、糖耐量减退,MS-Ht病理模型建立成功;然后将大鼠随机分为模型对照、二甲双胍(metformin,Met)200 mg/kg和TGP 150、50 mg/kg两个剂量组;分别灌胃给药或蒸馏水,qd×4周,实验结束时,测定大鼠血压、空腹血糖(FBG)和口服糖耐量试验2 h血糖(OGTT-2 hBG)、血浆胰岛素(Fins),并计算胰岛素敏感性(ISI)和胰岛素抵抗指数(HOMA-IRI);测定游离脂肪酸(FFA)、TNF-α、内皮素(ET-1)、肾素-血管紧张素(AngⅡ)、NO和丙二醛(MDA)含量以及一氧化氮合酶(NOS)和超氧化物歧化酶(SOD)活性。结果:与正常对照组比较,MS-Ht大鼠血压升高;FBG、OGTT-2hBG和Fins含量增高;ISI减弱、而HOMA-IRI增强;FFA、TNF-α、ET-1、肾素-AngⅡ和MDA含量增高(P<0.05或P<0.01);NO含量和NOS及SOD活性降低(P<0.05或P<0.01)。Met和TGP 150 mg/kg增强ISI,而降低HO-MA-IRI,纠正高胰岛素血症(P<0.05或P<0.01),降低FFA、TNF-α、ET-1、肾素-AngⅡ和MDA含量(P<0.05或P<0.01),提高NO含量和NOS及SOD活性;而Met能降低FBG、OG-TT-2 h BG含量(P<0.05或P<0.01);与TGP150 mg/kg组比较,差异无统计学意义(P>0.05);TGP 50 mg/kg组,除降低肾素、AngⅡ和FFA含量外(P<0.05),对其余指标,差异均无统计学意义(P>0.05)。结论:TGP和Met能对抗MS-Ht大鼠胰岛素抵抗、增强胰岛素敏感性、纠正高胰岛素血症,拮抗ET-1、肾素-AngⅡ系统和氧化应激反应,提高NO和NOS功能,降低血压;TGP不具直接降血糖作用,与Met不同。TGP以上效应呈量效关系。

AIM：To investigate the antihypertensive effects and effective mechanisms of total glucosides of paeong （TGP for short）on insulin resistance, hypertension, and the changes of oxidative stress in metabolic syndromic （MS）-hypertensive （Ht） rats. METHODS： The SD rats were fed with a high fat （ 25 % ）-sucrose （10%）- enriched diet qd for 8 weeks. When the rats were exposed hypertension and impaired glucose tolerance （IGT）,and the rats were randomly divided into normal control group, metformin （Met） group 200 mg/kg, and TGP 150, 50 mg/ kg, solvent or the drugs were adiministered by intragastric administration （ i. g. ） qd for 4 weeks. The blood pressure （BP）, the contents of fasting blood glucose （FBG）, 2-hours blood glucose after oral glucose tolerance test （2 h BGOGTT）, and fasting insulin （Fins） were determined, as well as the insulin sensitivity index （ISI） and insulin resistance index （HOMA-IRI） were calculated; the contents of free fatty acids （FFA）, TNF-α, endothelin （ET-1）, renin-angiotensinⅡ , NO,malonaldehyde （MDA） and activities of nitric oxide synthase （NOS） and superoxide dismutase （SOD） activity were determined after treatment. RESULTS.. Compared with normal control group, the BP and the contents of FBG, OGTT-2 h BG, Fins were incre-saed in MS-Ht rats, and ISI was weaken, HOMA-IRI was incresaed, the contents of FFA, TNF-α, ET-1, renin-Ang Ⅱ , MDA were incresaed;the content of NO, the activities of NOS and SOD were decreased（P〈0.05 or P〈0.01）. The ISI was incresaed, the HOMA-IRI was decreased,retrieve hyperinsulinemia（P〈0.05 or P 〈0.01）, the contents of FFA,TNF-α,ET-1,renin-Ang Ⅱ , MDA were decreased, the activities of NO, NOS, SOD were elevated in Met group and TGP 150 mg/kg group. Compared with TGP 150 mg/kg group, the contents of FBG, OGTT-2 h BG were decreased in Met group, there was no significant difference. CONCLUSION：TGP and Met are able to enhance the insulin sensitivity, retrieve hyperinsulinemia, Antagonism of ET-1, renin-Ang Ⅱ system and oxidative stress response, augment the function of NO, NOS, degrade the BP;TGP does not have a strong predominance against hyperglycaemia, TGP differs from Met. The effects of TGP show dose-effect relationship.