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。
Objective To investigate the effects of cyproheptadine on dexamethasone ( DEX ) -induced non -alcoholic fatty liver disease ( NAFLD ) in rats.Methods SD rats were divided randomly into 5 groups: normal group , model group with high , low dosage ( 2.5 , 1.0 mg· kg-1 ) DEX, high, low dosage (5.0 mg · kg -1 ) cyproheptadine treatment groups.Two weeks later after administration , all rats were killed.Body weight and liver weight of rats were measured.Level of serum liver function and lipoid index, glucose (GLU), free fatty acids ( FFA ) , fasting blood insulin ( FINS ) , adrenocorticotropic hormone ( ACTH) and corticosterone ( CORT) were detected.Rat primary hepato-cytes were isolated and treated with different concentration of DEX and cyproheptadine.The fatty droplets in cells were observed by oil red O staining under electron microscope.GLU in culture supernatant , intrace-llular trigly-ceride ( TG) and FFA levels were detected.Results DEX can cause disorders of glucose and lipid metabolism in rats.The level of alanine transarninase (ALT), aspartate aminotransferas (AST), blood fat, fasting blood glucose and insulin were higher than that of normal group.The hypothalamic pituitary adrenal ( HPA) axis was excessive ac-tivated and the level of ACTH and CORT were increased.While cyproheptadine can reduce the reactivity of HPA axis , improve glucose and lipid metabolism in rats.Similar results were obtained in the rat hepatocyte model tests.Conclusion Cyproheptadine can improve NAFLD induced by DEX in rats through the intervention of the HPA axis.
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2015年第7期511-514,518,共5页
The Chinese Journal of Clinical Pharmacology
基金
南京军区面上课题基金资助项目(10MA046)