中国临床药理学杂志
中國臨床藥理學雜誌
중국림상약이학잡지
THE CHINESE JOURNAL OF CLINICAL PHARMACOLOGY
2015年
7期
511-514,518
,共5页
王冰%朱月蓉%杨瑞宁%丁启龙%邱红
王冰%硃月蓉%楊瑞寧%丁啟龍%邱紅
왕빙%주월용%양서저%정계룡%구홍
赛庚啶%糖皮质激素%非酒精性脂肪肝%下丘脑-垂体-肾上腺皮质轴
賽庚啶%糖皮質激素%非酒精性脂肪肝%下丘腦-垂體-腎上腺皮質軸
새경정%당피질격소%비주정성지방간%하구뇌-수체-신상선피질축
cyproheptadine%glucocorticoid%non-alcoholic fatty liver disease%hypothalamic pituitary adrenal axis
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5.0,2.0 mg· 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。
目的:研究賽庚啶在地塞米鬆誘導的大鼠非酒精性脂肪肝( NAFLD)中的作用。方法 SD大鼠隨機分為5組,包括正常組、高與低2箇劑量模型組(地塞米鬆2.5,1.0 mg· kg-1)和高與低2箇劑量榦預組(賽庚啶5.0,2.0 mg· kg-1),實驗共進行14 d。實驗結束後,處死大鼠,稱體重、肝重,計算肝脂數;檢測血清肝功能與血脂指標和血糖、遊離脂肪痠、胰島素、促腎上腺皮質激素及皮質酮水平。分離大鼠肝細胞,加入不同濃度的地塞米鬆和賽庚啶,油紅O染色觀察肝細胞內脂滴的形成情況,檢測培養上清中糖和細胞內三酰甘油、遊離脂肪痠水平。結果與正常組相比,地塞米鬆可造成大鼠糖脂代謝紊亂,過度激活下丘腦-垂體-腎上腺皮質( HPA)軸,造成促腎上腺皮質激素、皮質酮水平升高。而賽庚啶可降低HPA軸的反應性,改善大鼠的糖脂代謝。在大鼠肝細胞模型實驗中得到相似的結果。結論賽庚啶可通過榦預機體HPA軸,改善地塞米鬆誘導的大鼠NAFLD。
목적:연구새경정재지새미송유도적대서비주정성지방간( NAFLD)중적작용。방법 SD대서수궤분위5조,포괄정상조、고여저2개제량모형조(지새미송2.5,1.0 mg· kg-1)화고여저2개제량간예조(새경정5.0,2.0 mg· kg-1),실험공진행14 d。실험결속후,처사대서,칭체중、간중,계산간지수;검측혈청간공능여혈지지표화혈당、유리지방산、이도소、촉신상선피질격소급피질동수평。분리대서간세포,가입불동농도적지새미송화새경정,유홍O염색관찰간세포내지적적형성정황,검측배양상청중당화세포내삼선감유、유리지방산수평。결과여정상조상비,지새미송가조성대서당지대사문란,과도격활하구뇌-수체-신상선피질( HPA)축,조성촉신상선피질격소、피질동수평승고。이새경정가강저HPA축적반응성,개선대서적당지대사。재대서간세포모형실험중득도상사적결과。결론새경정가통과간예궤체HPA축,개선지새미송유도적대서NAFLD。
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.