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利拉鲁肽调节脂肪酸的β-氧化改善非酒精性脂肪肝病大鼠症状
田 薇1,2
1.(1)昆明理工大学医学院,云南 昆明 650500;2)云南省第一人民医院干疗科,云南 昆明 650036)
摘要:
[摘要] 目的 探讨分析利拉鲁肽对高脂诱导的大鼠非酒精性脂肪肝病(non-alcoholic fatty liver disease,NAFLD)肝脏脂肪酸β-氧化关键酶过氧化物酶体增殖物激活受体α(Peroxisome Proliferators-Activated Receptor α,PPARα)和酶酰基辅酶A氧化酶1(Acyl Coenzyme A Oxidase1,ACOX1)表达的影响,以探讨其是否可以通过上述途径治疗NAFLD.方法 70只大鼠随机分为空白(20只)、模型(25只)以及利拉鲁肽治疗组(25只),模型成功建立后,利拉鲁肽治疗组给予利拉鲁肽60 μg/(kg.d)皮下注射治疗,模型组和空白组给予生理盐水注射参照,治疗4周和8周后分别处死大鼠各半,检测相关指标.结果 肝脏病理学可见,空白组细胞整齐光滑,细胞大小均一,没有任何脂肪浸润,模型组大鼠存在明显的肝脏脂肪沉积,治疗4周后,肝脏脂肪颗粒沉积明显减少,治疗8周后相较于4周组脂肪颗粒沉积进一步减少,但和空白组仍有有一定的差距;治疗组肝功能和血脂相较于模型组在治疗后均有明显的好转,同时其随着治疗时间的增加,进一步好转;与模型对照组相比,治疗4周后,治疗组大鼠肝脏PPARα、ACOX1 的蛋白和mRNA表达均有一定的升高,但差异无统计学意义(P>0.05),治疗8周后,2个蛋白表达相较于模型组有明显升高,差异有统计学意义(P<0.05).结论 利拉鲁肽可以明显改善高脂饮食诱导的大鼠脂肪代谢、改善肝功能,这可能是通过其增加脂肪酸β-氧化关键酶PPARα和ACOX1的表达,进而促进肝脏蓄积的脂肪酸的排出实现的.
关键词:  [关键词] 利拉鲁肽  非酒精性脂肪肝  大鼠  过氧化物酶体增殖物激活受体α
DOI:
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基金项目:[基金项目] 云南省科技厅-昆明医科大学联合专项基金资助项目(2011FB225);云南省科技厅应用基础研究基金资助项目(2013FZ183);云南省老年病防治研究中心基金资助项目(2014NS240)
Liraglutide Improves The Symptoms of Non-alcoholic Fatty Liver Disease by Regulating Fatty Acid β-oxidation
TIAN Wei1,2
1.(1)Medical Faculty of Kunming University of Science and Technology,Kunming Yunnan 650500;2)Dept. of Health Care,The First People’s Hospital of Yunnan Province,Kunming Yunnan 650036,China)
Abstract:
[Abstract]Objective To investigate and analyze the effect of Liraglutide on the expression of fatty acids β-oxidation key enzymes,Acyl Coenzyme A Oxidase1(ACOX1)and Peroxisome Proliferators-Activated Receptor α(PPARα),in high fat food induced Non-alcoholic Fatty Liver Disease( NAFLD)in rats,in order to investigate whether it can treat NAFLD through the above ways.Methods Severty rats were randomly divided into control, model and liraglutide group,after NAFLD model was successfully established,liraglutide treatment group received liraglutide 60 ug/(kg.d)treatment, model group and control group were given saline injections. 4 weeks and 8 weeks later,the rats were sacrificed to detect the correlated indexes.Results Liver pathology showed that cells were smooth and arranged regularly,cell size was uniform,and no fatty infiltration in control group,the presence of significant liver fat deposition in model group,4 weeks after treatment,liver fat deposition significantly reduced, 8 weeks after treatment,liver fat deposition significantly reduced further,but there was still a certain difference compared to the control group. After treatment,liver function and blood lipids were significantly improved;4 weeks after treatment,compared with the model group,in the treatment group liver PPARα and ACOX1 protein and mRNA expression increased, but the difference was not statistically significant, 8 weeks after treatment,both of them were significantly increased(P<0.05). Conclusion Liraglutide can significantly improve the high-fat diet-induced lipid,improve liver function, which may be related with the upregulation of fatty acids β-oxidation key enzymes PPARα and ACOX1, thus contributing to the discharge of the accumulated fatty acid in liver.
Key words:  [Key words]Liraglutide  NonAlcoholic fatty liver  Rat  Peroxisome proliferator-activated receptor α