决明子提取物对非酒精性脂肪肝大鼠的护肝、拮抗胰岛素抵抗和抗氧化糖基化作用

摘要

目的：探讨决明子乙醇提取物( semen cassiae extract,SCE)对高脂高糖诱导非酒精性脂肪肝大鼠血糖、血脂、胰岛素抵抗及肝功能和肝细胞脂肪变性病理改变以及氧化应激—糖基化作用。方法 SD大鼠72只,雌雄各半,随机分成正常对照组(12只)和模型组(60只)。正常对照组给予普通饲料,饮用蒸馏水；模型组大鼠给予高脂饲料,饮用10%果糖水。饲养至第6周末,将模型组大鼠随机分为模型对照组(蒸馏水10 mL/kg)、二甲双胍组(0．2 g/kg)、决明子乙醇提取物( SCE)高(2 g/kg)、中(1 g/kg)、低(0．5 g/kg)剂量组。连续灌胃给药4周后,测定大鼠血清超氧化物歧化酶( superoxide dismutase,SOD)、谷胱甘肽过氧化物酶( glutathione peroxidase,GSH-Px)、一氧化氮合成酶( nitric oxide synthase, NOS )活性,测定血清一氧化氮( nitric monoxide, NO )、丙二醛( malondialdehyde,MDA)、果糖胺( fructosamine, FMN )、晚期糖基化终产物( advanced glycation end products,AGEs)、葡萄糖含量( fasting blood glucose,FBG),血清胰岛素水平( insulin,INS)及胰岛素敏感度( insulin sensitivity index,ISI)。测定大鼠肝脏组织SOD、NOS活性及NO、MDA含量。结果与正常对照组相比,模型组大鼠血清GSP-Px、SOD和NOS活性降低,NO、MDA、FMN、AGEs、FBG含量升高,INS水平升高、ISI下降；模型组大鼠肝脏组织中SOD和NOS活性降低,NO和MDA含量明显升高(P<0．01)。 SCE和二甲双胍处理4周后,明显提高模型大鼠血清GSP-Px、SOD和NOS活性,降低NO、MDA、FMN、AGEs、FBG水平,并降低INS水平,上调ISI；同时,明显提高肝组织中SOD和NOS活性,降低NO、MDA含量(P<0．01,P<0．05),尤以SCE高剂量组作用更为明显。结论决明子提取物的护肝作用,与其拮抗胰岛素抵抗、增强抗氧化能力以及抑制氧化糖基化反应有关。%Objective To investigate the pathological changes of blood glucose, serum lipid, insulin resistance, liver function, liver cell denaturalization, and the oxidative-glycation effects of Semen Cassiae Extract( SCE) in rats with nonalcoholic fatty liver disease ( NAFLD) . Methods 72 SD rats were randomly divided into normal group (12) and model group (60). The normal rats were raised by standard animal diet, while the model rats were fed with high-fat diet and 10% fructose for 6 weeks. Model rats were randomly divided into 5 groups, including fatty liver group, metformin group (0. 2g·kg-1 ), SCE high-dose group (2g·kg-1), middle-dose group(1g·kg-1) and low-dose group (0. 5g·kg-1). All rats were treated for 4 weeks with drugs. The contents or activities of SOD, GSP-Px, NOS, NO, MDA, FMN, AGEs, FBG, INS in the serum and contents or activities of SOD, NOS, NO, MDA in the liver tissue were respectively measured, and ISI was counted. Results Compared with normal rats, the contents of or activities NOS, NO, MDA, FMN, AGEs, FBG, INS in the serum and contents or activities of NOS, NO, MDA in the liver tissue were increased ( P<0. 01 ) , but the activities of SOD, GSP-Px and ISI were decreased ( P<0. 01 ) in model rats. After SCE treatment for 4 weeks, compared with model rats, The contents or activities of SOD, GSP-Px, NOS, NO, MDA, FMN, AGEs, FBG, INS in the serum and contents or activities of NOS, NO, MDA in the liver tissue were decreased respectively, but the activities of SOD, GSP-Px and ISI were increased. Conclusion SCE possess hepatoprotective effect on structures or functions by antagonizing insulin resistance, enhancing the antioxidant capacity and inhibiting oxidative-glycation in rats with NAFLD.