Effects of fermented Chaenomeles speciosa juice on lipid metabolism and AMPK / SIRT1 pathway in mouse with non- alcoholic fatty liver disease
-
摘要: 目的:观察木瓜发酵液对高糖高脂饲料诱导的非酒精性脂肪性肝病(NAFLD)小鼠脂质代谢及AMP激活蛋白酶(AMPK)/沉默信息调节因子1(SIRT1)通路的调控机制。方法:取雄性昆明小鼠32只,随机分为4组,即正常组、模型组、木瓜发酵液高(10 m L/kg)和低剂量组(5 m L/kg),每组8只。三周后,收集小鼠血液及组织样本。用试剂盒检测血清ALT、肝组织甘油三酯(TG)含量,分别用RT-PCR和Western Bloting检测p-AMPK和SIRT1基因的mRNA和蛋白表达水平。结果:与正常组比较,模型组小鼠病理证实肝组织脂质蓄积严重,血清ALT和肝脏TG水平明显升高(p<0.05),肝组织SIRT1、Fox O1和p-AMPK mRNA及蛋白表达均显著降低(p<0.05)。与模型组比较,木瓜发酵液明显改善肝组织脂质蓄积,肝组织TG含量明显下降(p<0.05),肝组织SIRT1、Fox O1 mRNA和SIRT1、p-AMPK蛋白表达均显著上调(p<0.05),其中木瓜发酵液高剂量组较低剂量组效果好,但二者比较差异无统计学意义。结论:木瓜发酵液能够改善高糖高脂饮食诱导的NAFLD小鼠脂肪代谢紊乱,减轻肝脏脂质蓄积,其作用机制可能与肝细胞内AMPK/SIRT1通路的激活有关。
-
关键词:
- 木瓜发酵液 /
- 非酒精性脂肪性肝病 /
- AMPK/SIRT1通路 /
- 脂质代谢
Abstract: Objective: To observe the effects of fermented Chaenomeles speciosa Juice( FCJ) on the lipid metabolism and AMPK / SIRT1 pathway of non- alcoholic fatty liver disease( NAFLD) mice induced by high sugar and fat diet. Methods: Thirty- two SPF male Kunming mice were divided randomly into four groups: the control group,the model group,the high- dose FCJ- treated group( 10 m L / kg),and the low- dose FCJ- treated group( 5 m L/kg). After the treatment of three weeks,the blood and liver samples were collected.The activity of ALT in serum and triglyceride( TG) in liver tissues were detected with detection kits. The histology of liver tissues was observed with HE and red oil O staining. The mRNA and protein expression levels of p- AMPK and SIRT1 in liver tissues were measured with RT- PCR and Western Bloting.Results: Compared with the normal group,hepatic lipid accumulation of model group was severe showed by histopathological examination,the serum levels of ALT and TG in the liver tissue were increased significantly( p < 0.05),the expression levels of SIRT1,Fox O1 mRNA and SIRT1,P- AMPK protein of liver tissues were significantly decreased( p < 0.05). Compared with the model group,the hepatic lipid accumulation in FCJ- treated groups was obviously ameliorated,the serum ALT and TG levels of FCJ- treated groups were significantly decreased( p < 0.05),the expression levels of hepatic SIRT1,Fox O1 mRNA and p- AMPK,SIRT1 protein in FCJ- treated groups were significantly up- regulated( p < 0.05). The effect of high dose group was better than the low dose group,but the two were not statistically significant. Conclusion: FCJ canameliorate the disorder of lipid metabolism in the NAFLD mice induced by feeding high sugar and fat diet,and the mechanism may be related to the activation of AMPK / SIRT1 pathway in hepatocytes. -
[1] Mishra A,Younossi Z M.Epidemiology and natural history of non-alcoholic fatty liver disease[J].La Revue Du Praticien,2012,62(10):135-144.
[2] Goyal N P,Schwimmer J B.The progression and natural history of pediatric non-alcoholic fatty liver disease[J].Clinics in Liver Disease,2016,20(2):325-338.
[3] Santamarina A B,Oliveira J L,Silva F P,et al.Green tea extract rich in Epigallocatechin-3-Gallate prevents fatty liver by AMPK activation via LKB1 in mice fed a high-fat diet[J].Plos One,2014,10(11):1-18.
[4] 汤超,汤文凡,刘朝奇,等.木瓜发酵液对小鼠四氯化碳诱发肝损伤的防护作用[J].食品科学,2013,34(13):271-274. [5] 焦新生,刘朝奇,逯平杰,等.木瓜发酵工艺及其抗氧化活性研究[J].中华中医药杂志,2009(S1):97-99. [6] Salomone F,Godos J,Zelber-Sagi S.Natural antioxidants for non-alcoholic fatty liver disease:molecular targets and clinical perspectives[J].Liver International Official Journal of the International Association for the Study of the Liver,2016,36(1):5-20.
[7] Ajmera V H,Vanwagner L B,Gunderson E P,et al.461gestational diabetes mellitus is strongly associated with nonalcoholic fatty liver disease[J].Gastroenterology,2016,111(5):658-664.
[8] Salomone F,Godos J,Zelber-Sagi S.Natural antioxidants for non-alcoholic fatty liver disease:molecular targets and clinical perspectives[J].Liver International Official Journal of the International Association for the Study of the Liver,2016,36(1):5-20.
[9] Young Mi S,Yong-Ho L,Ji-Won K,et al.Metformin alleviates hepatosteatosis by restoring SIRT1-mediated autophagy induction via an AMP-activated protein kinase-independent pathway[J].Autophagy,2015,11(1):46-59.
[10] 邹传宗.木瓜活性成分及药理作用研究概述[J].园艺与种苗,2012(3):55-58. [11] Yang Y,Li W,Liu Y,et al.Alpha-lipoic acid improves high fat diet-induced hepatic steatosis by modulating the transcription factors SREBP-1,Fox O1 and Nrf2 via the SIRT1/LKB1/AMPK pathway[J].Journal of Nutritional Biochemistry,2014,25(11):1207-1217.
计量
- 文章访问数: 163
- HTML全文浏览量: 27
- PDF下载量: 374