摘要
目的探讨利拉鲁肽对2型糖尿病非酒精性脂肪肝病的保护作用及机制。方法选取50只小鼠,随机分为正常对照组(15只)和高糖高脂饲料组(35只),采用高糖高脂饲料联合小剂量链脲佐菌素的方法,建立2型糖尿病非酒精性脂肪肝病的小鼠模型,经处理分为正常对照组、模型对照组、利拉鲁肽组,每组10只。利拉鲁肽皮下注射8周,观察各组空腹血糖(FBG)、丙氨酸氨基转移酶(ALT)和天门冬氨酸氨基转移酶(AST)活性、胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)及肝指数等指标;检测肝组织超氧化物歧化酶(SOD)、丙二醛(MDA)、肿瘤坏死因子-α(TNF-α)、白细胞介素-8(IL-8)的水平;采用HE染色及油红"O"染色观察肝组织病理改变;采用免疫组织化学法检测肝组织中B淋巴细胞瘤-2(Bcl-2)、Bcl-2相关X蛋白(BaX)的表达。结果与正常对照组比较,模型对照组大鼠的FBG、FINS、HOMA-IR增高,血清TG、TC、ALT、AST含量升高,肝指数增高,肝组织中SOD活性降低、MDA含量升高、TNF-α及IL-8水平上升,HE染色、油红"O"染色肝组织中脂肪性变明显,Bcl-2蛋白表达明显减少,BaX蛋白表达明显增加(P<0.01,P<0.05)。与模型对照组比较,利拉鲁肽组的FBG、TG、TC、ALT、AST含量降低,HOMA-IR及肝指数下降;肝组织中SOD活性升高,MDA含量及TNF-α、IL-8水平下降(P<0.01);HE染色、油红"O"染色肝组织中脂肪性变明显减轻,Bcl-2蛋白表达明显增加,BaX蛋白表达明显降低(P<0.01)。结论利拉鲁肽对2型糖尿病非酒精性脂肪肝病的小鼠肝脏具有保护作用,其机制可能与其抗氧化作用、减少炎症因子的表达及调节凋亡相关蛋白Bcl-2、BaX的表达有关。
Objective To explore the protective effect and mechanism of Liraglutide on non-alcoholic fatty liver disease in mice with type2diabetes mellitus.Methods A total of50mice were selected and randomly divided into normal control group(n=15)and high-suger and high-fat diet group(n=35).A non-alcoholic fatty liver disease model of type2diabetes mellitus by high-sugar and high-fat diet combined with low-dose streptozotocin was established.The mice were divided into the normal control group,the model control group,and the liraglutide group after treatment,with10cases in each group.Liraglutide was injected subcutaneously for8weeks.Fast blood glucose(FBG),alanine amino-transferase(ALT)and aspartate aminotransferase(AST),insulin(FINS),insulin resistance index(HOMA-IR)and liver index were observed in each group.The level of SOD,MDA,TNF-α,IL-8in liver tissue were detected.HE staining and oil red“O”staining were used to observe the pathological changes of liver tissue.Immunohistochemistry was used to detect the expression of B-lymphoma-2(Bcl-2)and Bcl-2related X-protein(BaX)in liver tissue.Results Com-pared with the normal control group,the level of FBG,FINS and HOMA-IR in model control group increased,the level of serum TG,TC,ALT,AST content increased,the level of liver index increased,SOD activity decreased,MDA content increased,TNF-αand IL-8levels increased,HE staining and oil red“O”staining in liver tissue fatty change was ob-vious,Bcl-2protein expression significantly decreased,and BaX protein expression increased significantly(P<0.01,P<0.05).Compared with the model control group,the contents of FBG,TG,TC,ALT,AST,HOMA-IR and liver index de-creased,SOD activity increased,MDA content,TNF-αand IL-8decreased in the Liraglutide group(P<0.01).HE staining and oil red“O”staining significantly reduced fatty degeneration,the expression of Bcl-2protein significantly increased and the expression of BaX protein significantly decreased(P<0.01).Conclusion Liraglutide has protective ef-fects on the liver of non-alcoholic fa
作者
邢冬杰
宿世震
陈桂玉
张彩坤
宋桂红
刘晓庆
XING Dong-jie;SU Shi-zhen;CHEN Gui-yu;ZHANG Cai-kun;SONG Gui-hong;LIU Xiao-qing(Shandong College of Traditional Chinese Medicine, Yantai 264199, China)
出处
《中国当代医药》
2018年第33期12-15,25,共5页
China Modern Medicine
基金
山东省医药卫生科技发展计划项目(2015WS0127)
