虎杖苷对非酒精性脂肪性肝病胰岛素抵抗及氧化应激影响的实验研究

[目的]研究虎杖苷治疗对非酒精性脂肪性肝病（NAFLD）胰岛素抵抗（IR）及氧化应激的影响。[方法]健康雄性SD大鼠47只，随机分为5组：正常组（10只）、模型组（10只）、虎杖苷大剂量组（9只）、虎杖苷小剂量组（9只）和双环醇组（9只）。正常组予标准饲料，其他4组给予高脂饲料造模；5组共喂养10周后，从正常组与模型组中各随机挑选1只大鼠，取肝脏做病理切片，证实大鼠NAFLD模型的形成。正常组与模型组予以0．9％氯化钠灌胃，5ml／次；虎杖苷大、小剂量组分别以200mg／（kg·d）、100mg／（kg·d）的虎杖苷混悬液灌胃；双环醇组以100mg／（kg·d）的双环醇混悬液灌胃。给药4周，期间各组大鼠统一用标准饲料饲养。次日大鼠禁食12h后，腹腔麻醉，抽取腹主动脉血5ml，分离血清，检测大鼠血清中氧化应激因子丙二醛（MDA）、总超氧化物歧化酶（T-SOD）、羟自由基（-OH）、谷胱甘肽一孓转移酶（GST）水平及血清总抗氧化能力（T-AOC）水平；试剂盒检测空腹血糖、胰岛素水平，计算IR指数（IRI）和胰岛素敏感指数；ELISA法检测大鼠血清肿瘤坏死因子-α（TNF-α）水平。[结果]高脂饮食饲养10周后，模型组大鼠血清-OH、MDA、TNF-α较正常组均显著增高（P〈0．05～〈0．01），GST、T-SOD、T-AOC活性降低（P〈0．01），与模型组相比，虎杖苷治疗后，-OH、MDA、TNF-α浓度降低（P〈0．05〈0．01），而T-SOD及T-AOC的活性恢复（P〈0．05～〈0．01），IR明显改善（P〈0．05～〈0．01）。[结论]IR和氧化应激关系密切，氧化应激是发生IR的重要原因之一，虎杖苷的抗氧化应激效应是改善IR的部分机制。

The effects of polydatin on insulin resistance and oxidative stress in nonalcoholic fatty liver disease

[Objective]To explore the effect of polydatin on insulin resistance（IR） and oxidative stress of non alcoholic fatty liver disease （NAFLD）. EMethods] Forty-seven healthy male SD rats were randomly di- vided into normal group（10 rats）, model group（10 rats）, high dose of polydatin group （9 rats）, low dose of polydatin group（9 rats）and bicyclol group（9 rats）. Normal group received standard diet. The other 4 groups were fed with high fat diet. After 10 weeks of feeding, one rat was randomly selected from both normal group and model group. The liver pathological slices were observed to confirm the establishment of NAFLD of rats. The rats in each group were treated for 4 weeks. After treatment, rats were sacrificed to measure oxidative stress factors malondialdehyde（MDA）, superoxide dismutase（T-SOD）,hydroxyl radical （-OH） ,glutathione-S- transferase （GST）, total antioxidant capacity of T-AOC level, fasting blood glu- cose,fasting insulin,insulin resistance index and insulin sensitive index. ELISA was used to measure the serum TNF-α level. [Results]Serum hydroxyl radical, MDA, TNF-α in the model group were significantly higher than those in the control group（P〈0. 05, 〈0.01）. SOD, T-SOD and T-AOC activity were decreased in model group compared to control group（P〈 0.01）. After the treatment with polydatin,hydroxyl radi- cal, MDA, the concentration of TNF-α were decreased （P〈0. 01）, and SOD, T-SOD and T-AOC activity were reversed（P〈 0. 01）. IR was also improved significantly（P（ 0. 01）. [Conelusion] There is close re- lationship between IR and oxidative stress, suggesting that oxidative stress is one of the important causes of IR. Polydatin relieves IR partly via anti-oxidative stress.