机构地区:[1]广州市中医医院,广东广州510130 [2]广州市中医中药研究所,广东广州510130 [3]暨南大学药学院,广东广州510632
出 处:《中国医院药学杂志》2011年第11期878-883,共6页Chinese Journal of Hospital Pharmacy
基 金:广东省医学科学技术基金资助项目(编号:A2004546)
摘 要:目的:研究栀子提取物对高脂诱导胰岛素抵抗-脂肪肝大鼠血糖、血脂、胰岛素抵抗及肝功能和肝细胞肪变性病理改变的作用。方法:用高脂、高糖饲料喂养大鼠,饲养56d,第57天测定大鼠空腹血糖(FBG)和口服耐量试验2h血糖(OGTT-2hBG),并依血糖和体质量将大鼠均衡随机分为脂肪肝模型对照组,水飞蓟宾组:0.154g.kg-1,栀子高剂量组:3.6g.kg-1,栀子低剂量组:1.8g.kg-1;连续灌胃给药28d后,测定大鼠FBG,OGTT-2hBG和血清胰岛素(Fins)水平,并计算胰岛素抵抗指数(HOMA-IRI)和胰岛素敏感指数(ISI);测定血浆三酰甘油(TC)、总胆固醇(TG)、低密度脂蛋白(LDL-C)、高密度脂蛋白(HDL-C)、游离脂肪酸(FFA)水平;测定天门冬氨氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、胆碱脂酶(ChE)、超氧化物歧化酶(SOD)、一氧化氮合酶(NOS)活性以及丙二醛(MDA)和一氧化氮(NO)含量等的变化,并评估肝组织脂肪变性。结果:与正常大鼠比较,模型组大鼠胰岛素含量和IRI明显升高(P<0.01),而ISI降低(P<0.01),水飞蓟宾及栀子3.6g.kg-1和1.8g.kg-1均有降低FBG和OGTT-2h BG含量的趋势,但差异无显著性(P>0.05);FFA,TG,TC和LDL-C水平升高(P<0.01),HDL-C水平降低(P<0.05);NO含量及NOS和SOD活性降低(P<0.01),MDA含量升高(P<0.01);AST,ALT和ChE活性增高(P<0.05,P<0.01);肝脏脂肪变性明显增强(P<0.01)。栀子提取物和水飞蓟宾均能不同程度地拮抗大鼠的高胰岛素血症和胰岛素抵抗(P<0.05,P<0.01);降低FFA,TG,TC和LDL-C水平以及提高HDL-C含量(P<0.05,P<0.01);降低AST,ALT和ChE活性P<0.05,P<0.01);提高SOD和NOS活性(P<0.01),并降低MDA含量(P<0.05);但栀子1.8g.kg-1作用不明显(P>0.05)。结论:栀子提取物对胰岛素抵抗-脂肪肝具有降血脂和保肝作用,其作用机制可能与其提高胰岛素敏感性、降低血脂以及增强抗氧化能力有关。OBJECTIVE To study the effects of Gardenia extract on pathological changes of blood glucose, serum lipid, in- sulin resistance, liver function, liver cell denaturalization in nonalcoholic fatty liver rats caused by insulin resistance, and discuss the mechanism of its actions. METHODS Adult SD rats were maintained on high-fat-sugar-salt-diet for 56 days. In the 57th day, their fasting blood gluose (FI3G) and 2-hours blood glucose after oral glucose tolerance test (OGTT-2 hBG) were meas- ured, according to which the rats were divided randomly into nonalcoholic fatty livermodelgroup, Silibinin group (0. 154 g·kg ^-1) and Gardenia extract group (high dosage 3.6 g·kg ^-1 , low dosage 1.8g·kg ^-1 ). All the rats were still administered the same diet and given different drugs by intragastric administration for 28 days. In the 29 day, the rats were killed and the blood was sampled to measure the levels of blood glucose [FBG, OGTT-2 hBG, fasting insulin (Fins)] and serum lipid FFA, TG, TC, LDL-C, HDL-C, then the HOMA insulin resistance index (HOMA-IRI) and insulin sensitivity index (ISI) were counted. The activities of AST, ALT,ChE, SOD, NOS, MDA, NO were measured also. Livers were weighed and collected to observe the pathological changes. RESULTS Compared with normal group, in nonalcoholic fatty liver model group the levers of Fins and IRI were increased obviously (P〈0. 01), ISI were decreased (P〈0. 01), Silibinin and gardenia (3. 6 g·kg ^-1 and 1.8 g·kg ^-1 ) had the tendency to reduce FBC- and the content of OGTT-2h BG however, no significant difference(P〉0. 05) , FFA, TG, TC, LDL-C were increased (P〈0. 01), HDL-C were decreased (P〈0. 05) ; the content of MDA were increased (P〈 0. 05), the activities of NO content and NOS and SOD were decreased (P〈0. 01) ; AST, ALT and ChE were increased (P〈 0. 05, P〈0. 01), the pathological changes of liver fatwere severe (P〈0. 01). In Gardenia extract group and silibinin group, hyperinsulinae
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