赛庚啶对糖皮质激素诱导的大鼠非酒精性脂肪肝的保护作用研究

发布时间：2018-08-07 21:54

【摘要】：目的研究赛庚啶在地塞米松诱导的大鼠非酒精性脂肪肝(NAFLD)中的作用。方法 SD大鼠随机分为5组,包括正常组、高与低2个剂量模型组(地塞米松2.5,1.0 mg·kg-1)和高与低2个剂量干预组(赛庚啶5.0,2.0mg·kg-1),实验共进行14 d。实验结束后,处死大鼠,称体重、肝重,计算肝脂数;检测血清肝功能与血脂指标和血糖、游离脂肪酸、胰岛素、促肾上腺皮质激素及皮质酮水平。分离大鼠肝细胞,加入不同浓度的地塞米松和赛庚啶,油红O染色观察肝细胞内脂滴的形成情况,检测培养上清中糖和细胞内三酰甘油、游离脂肪酸水平。结果与正常组相比,地塞米松可造成大鼠糖脂代谢紊乱,过度激活下丘脑-垂体-肾上腺皮质(HPA)轴,造成促肾上腺皮质激素、皮质酮水平升高。而赛庚啶可降低HPA轴的反应性,改善大鼠的糖脂代谢。在大鼠肝细胞模型实验中得到相似的结果。结论赛庚啶可通过干预机体HPA轴,改善地塞米松诱导的大鼠NAFLD。
[Abstract]:Objective to study the effect of cyproheptadine on dexamethasone induced non-alcoholic fatty liver (NAFLD) in rats. Methods Sprague-Dawley rats were randomly divided into 5 groups, including normal group, high and low dose model group (dexamethasone 2.5U 1.0 mg kg-1) and high and low dose intervention groups (cyproheptadine 5.0 mg kg-1) for 14 days. At the end of the experiment, the rats were killed to weigh weight, liver fat number, serum lipids, blood glucose, free fatty acid, insulin, adrenocorticotropic hormone and corticosterone levels. Rat hepatocytes were isolated, dexamethasone and cyproheptadine were added at different concentrations. Lipid droplets in hepatocytes were observed by oil red O staining, and the levels of sugar, triglyceride and free fatty acids in cultured supernatants were detected. Results compared with the normal group, dexamethasone could cause the disorder of glucose and lipid metabolism, over-activate the (HPA) axis of hypothalamus-pituitary-adrenal cortex, and increase the levels of corticotropin and corticosterone. Cyproheptadine could decrease the reactivity of HPA axis and improve the metabolism of glucose and lipid in rats. Similar results were obtained in rat hepatocyte model. Conclusion cyproheptadine can improve the dexamethasone induced NAFLD by interfering with the HPA axis.
【作者单位】：解放军第81医院检验科;中国药科大学药学医学基础实验教学中心;
【基金】：南京军区面上课题基金资助项目(10MA046)
【分类号】：R965

【参考文献】