白藜芦醇通过诱导自噬改善高脂饮食小鼠非酒精性脂肪肝

Resveratrol Induces Autophagy and Its Interference Effect on Experimental Nonalcoholic Fatty Liver Mice

目的探讨自噬在白藜芦醇(Res)改善高脂饮食诱导的非酒精性脂肪性肝病(NAFLD)小鼠中的作用。方法采用高脂饮食8周建立小鼠NAFLD模型。造模成功后,模型组予高脂饲料+生理盐水10m L/kg灌胃,观察组予高脂饲料+Res100mg/kg灌胃,1天1次,连续2周。正常对照组始终予基础饲料。检测各组小鼠血清总胆固醇(TC)、甘油三酯(TG)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、空腹血糖(FBG)水平及胰岛素抵抗指数(HOMA-IR)。Western blot检测自噬相关蛋白p62及通路蛋白磷脂酰肌醇-3-羟基激酶(PI3K)、丝氨酸-苏氨酸激酶(AKt)、哺乳动物雷帕霉素靶蛋白(m TOR)的表达水平。结果与正常对照组比较,模型组、观察组血清TG、TC、ALT、AST水平及HOMA-IR均显著升高(P<0.05);与模型组比较,观察组上述指标均显著降低[(1.86±0.18)mmol/L比(4.55±0.28)mmol/L,(5.36±0.31)mmol/L比(8.79±0.35)mmol/L,(55.62±4.35)U/L比(154.18±8.33)U/L,(86.54±5.26)U/L比(297.47±8.96)U/L,(1.64±0.22)比(2.26±0.23),P<0.05]。与正常对照组比较,模型组小鼠肝组织中p62、PI3K、磷酸化(p)-Akt、p-m TOR水平均显著升高;与模型组比较,观察组上述指标均显著降低[(1.04±0.07)比(1.45±0.08),(0.96±0.07)比(1.52±0.06),(0.94±0.08)比(1.64±0.08),(0.59±0.02)比(1.12±0.04),P<0.05]。结论 Res可能通过抑制PI3K/Akt/m TOR信号通路进而促进自噬,最终发挥改善NAFLD小鼠脂代谢、IR和肝功能的作用。

Objective To investigate the role of autophgy in the effect of resveratrol（Res） on experimental nonalcoholic fatty liver（NAFLD） mice. Methods Mice were modelled into NAFLD by using high fat diet for 8 weeks.After the modelling, mice in model group was given a high-fat forage＋saline 10 m L/kg, 1 lavage per day and observation group was given the same high-fat forage＋Res 100 mg/kg, 1 lavage per day, both for continuous 2 weeks.Normal control group had access to the basal feedstuff. The level of total cholesterol（TC）, triglyceride（TG）, alanine aminotransferase（ALT）, aspartate aminotransferase（AST）, fasting blood glucose（FBG） level and insulin resistance index（HOMA-IR） was detected, the expression of autophagy related protein p62 and protein pathway was assessed with Western Blot. Results CCompared with normal control group, model group and observation group had higher serum levels of TG, TC, ALT, AST and HOMA-IR（P〈0.05）. Compared with those of model group, the above indexes of observation group were significantly lower, respectively（1.86 ±0.18 mmol/L vs 4.55 ±0.28 mmol/L, 5.36 ±0.31 mmol/L vs 8.79±0.35 mmol/L, 55.62±4.35 U/L vs 154.18±8.33 U/L, 86.54±5.26 U/L vs 297.47±8.96 U/L, 1.64±0.22 vs 2.26±0.23; all P〈0.05）. Compared with normal control group, model group had higher levels of p62, PI3 K, pm TOR and p-Akt（P〈0.05）, but these index in observation group were significantly decreased compared with model group（1.04±0.07 vs 1.45±0.08, 0.96±0.07 vs 1.52±0.06, 0.94±0.08 vs 1.64±0.08, 0.59±0.02 vs 1.12±0.04; all P〈0.05）. Conclusion Res may promote autophagy by inhibiting the PI3 K/Akt/m TOR signaling pathway, and ultimately play a role in improving the lipid metabolism, IR and liver function of NAFLD.