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目的研究热卡限制(CR)在非酒精性脂肪肝病(NAFLD)治疗中的分子作用机制。方法 25只雄性 Wistar 大鼠分为2组,一组给予正常普通饲料喂养(NC 组,7只),一组给予高脂饲料喂养(HFM 组,18只)。喂养2个月后,再将 HFM 组大鼠随机分为继续高脂饲料喂养组(HF 组,9只)和60%热卡限制喂养组(CR 组,9只)。1个月后将大鼠处死,观察大鼠体重、内脏脂肪含量、空腹血糖、空腹胰岛素及血脂的改变,电镜下观察各组大鼠肝脏超微结构变化,应用 RT-PCR 方法检测长寿基因 SIRT1 mRNA 的表达,Westerm 印迹法检测 SIRT1的蛋白表达。结果 HF 组大鼠发生明显NAFLD,与正常对照组比较,大鼠内脏脂肪含量(15.1 g±4.1 g vs 9.0 g±0.4 g)、血脂(总胆固醇2.61 mmol/L±0.29 mmol/L vs 1.41 mmol/L±0.28 mmol/L;甘油三酯1.35 mmol/L±0.21 mmol/L vs0.67 mmol/L±0.10 mmol/L)、血糖(6.2 mmol/L±1.46 mmol/L vs 4.4 mmol/L±0.57 mmol/L),血胰岛素水平(29.22 mU/L±7.28 mU/L vs 13.09 mU/L±1.18 mU/L)明显增高,其肝脏超微结构亦发生明显异常,SIRT1表达在转录和翻译水平均低于正常组显著(P<0.01)。相比较 HF 组,限制热忙后的 CR 组大鼠体重明显下降,内脏脂肪含量、血脂、血糖、血胰岛素水平显著降低,SIRT1的表达明显增加(P<0.01),同时肝细胞的超微病理改变亦显著改善。结论 CR 对大鼠 NAFLD 具有显著的逆转效应,其导致的肝脏 SIRT1表达增加可能是改善 NAFLD 的重要分子作用机制。
Objective To investigate the molecular mechanism of heat card restriction (CR) in the treatment of non-alcoholic fatty liver disease (NAFLD). Methods Twenty - five male Wistar rats were divided into two groups. One group was fed with normal diet (NC group, 7 mice) and the other group was fed with high fat diet (HFM group, 18 mice). After feeding for 2 months, the rats in HFM group were randomly divided into continuous high fat diet group (HF group, n = 9) and 60% calorie restriction group (n = 9). After 1 month, the rats were sacrificed and the changes of body weight, visceral fat, fasting blood glucose, fasting insulin and lipids were observed. The ultrastructure of liver in each group were observed under electron microscope. The expression of longevity gene SIRT1 The mRNA expression of SIRT1 was detected by Westerm blotting. Results Compared with the normal control group, visceral fat content (15.1 g ± 4.1 g vs 9.0 g ± 0.4 g), blood lipid (total cholesterol 2.61 mmol / L ± 0.29 mmol / L vs 1.41 mmol /L ± 0.28 mmol / L; triglyceride 1.35 mmol / L ± 0.21 mmol / L vs 0.67 mmol / L ± 0.10 mmol / L), blood glucose (6.2 mmol / L ± 1.46 mmol / L vs 4.4 mmol / L ± 0.57 mmol / L). The level of insulin (29.22 mU / L ± 7.28 mU / L vs 13.09 mU / L ± 1.18 mU / L) was significantly increased. All lower than the normal group (P <0.01). Compared with HF group, body weight of CR rats decreased significantly, body fat, blood lipids, blood glucose, blood insulin levels significantly decreased, and the expression of SIRT1 significantly increased (P <0.01), while the ultrastructural changes of hepatocytes Changes have also significantly improved. Conclusion CR has a significant reversal effect on NAFLD in rats. The increased expression of SIRT1 in the liver may be an important molecular mechanism for the improvement of NAFLD in rats.