高血糖对非酒精性脂肪性肝炎大鼠肝脏超微结构及细胞凋亡的影响  

Effects of hyperglycemia on liver ultrastructure and apoptosis in rats with nonalcoholic fatty liver disease

作　　者：常业飞 胡滔 洪颖 钟勇 王宏刚 高迪 郑盛 CHANG Yefei;HU Tao;HONG Ying;ZHONG Yong;WANG Honggang;GAO Di;ZHENG Sheng(Department of Clinical Laboratory,Yunnan Third People′s Hospital,Kunming,Yunnan 650011,China)

机构地区：[1]云南省第三人民医院检验科,云南昆明650011

出　　处：《国际检验医学杂志》2018年第18期2234-2237,2241,共5页International Journal of Laboratory Medicine

基　　金：云南省教育厅科学研究基金项目(2016ZDX112)

摘　　要：目的探讨高血糖对非酒精性脂肪性肝炎(NAFLD)大鼠肝脏超微结构及细胞凋亡的影响。方法将58只SPF级雄性大鼠采用随机数字表法分为正常组(n=10)、高血糖模型组(n=12)、复合模型组(高血糖合并NAFLD,n=12)、氨基胍组(n=12)、格列美脲组(n=12),检测各组血糖值,在电镜下观察肝脏超微结构,应用TUNEL染色法观察肝细胞凋亡情况,以酶联免疫吸附试验测定血浆基质金属蛋白酶抑制因子-1(TIMP-1)、转化生长因子β1(TGF-β1)、晚期糖基化终产物(AGEs)水平。结果氨基胍组、格列美脲组大鼠血糖值低于高血糖模型组、复合模型组(P<0.05),且氨基胍组血糖值高于正常组(P<0.05),格列美脲组血糖值与正常组比较,差异无统计学意义(P>0.05)。与正常组比较,高血糖模型组、复合模型组肝组织出现细胞超微结构改变,核周围存在脂滴,且肝细胞浆中线粒体、内质网变形;而与复合模型组比较,格列美脲组肝细胞超微结构较正常,可观察到核周围脂滴分布明显改善,线粒体及内质网形态趋于正常,而氨基胍组核周围脂滴分布、线粒体与内质网形态有所改善。肝细胞凋亡率大小:复合模型组>高血糖模型组>正常组,复合模型组、高血糖模型组>格列美脲组(P<0.05)。各组血浆TIMP-1、TGF-β1、AGEs水平排序均为:复合模型组>高血糖模型组>正常组,复合模型组>氨基胍组、格列美脲组(P<0.05)。结论高血糖可能会促进NAFLD大鼠肝纤维化、肝脏超微结构改变及肝细胞凋亡,降低血糖或减少TIMP-1、TGF-β1、AGEs,有助于减轻或抑制肝脏超微结构改变及肝细胞凋亡。Objective To explore the effects of hyperglycemia on liver ultrastructure and apoptosis in rats with nonalcoholic fatty liver disease （NAFLD）. Methods Totally 58 cases of SPF male rats were divided into the normal group （ n =10）,the hyperglycemia model group （ n =12）,the complex model group （hyperglycemia complicated with NAFLD, n =12）,the aminoguanidine group （ n =12） and the glimepiride group （ n =12）.Blood glucose levels were measured among the groups and the ultrastructure of the liver was observed under electron microscope,and the apoptosis of liver cells was observed by TUNEL staining.The levels of plasma matrix metalloproteinase inhibitor -1 （TIMP-1）,transforming growth factor-β1 （TGF-β1） and advanced glycation end products （AGEs） were determined by enzyme-linked immunosorbent assay. Results The rats blood glucose value in the aminoguanidine group and the glimepiride group was lower than the hyperglycemia model group and the complex model group （ P 〈0.05）,and the value in the aminoguanidine group was higher than that in the normal group （ P 〈0.05）,and there was no significant difference in the value between the glimepiride group and the normal group （ P 〉0.05）.Compared with the normal group,ultrastructural changes were observed in the liver tissue and there were lipid droplets around the nucleus,and the deformity of mitochondria and endoplasmic reticulum in the liver cells cytoplasm in the hyperglycemic model group and the complex model group.Compared with the complex model group,the ultrastructure of liver cells was in normal condition,and the lipid droplet distribution around the nucleus was improved obviously and the morphology of mitochondria and endoplasmic reticulum was back to the normal condition in the glimepiride group while the lipid droplets distribution around the nucleus and the morphology of mitochondria and endoplasmic reticulum were improved in the aminoguanidine group.The comparison of the hepatocyte apoptosis size was that：the c

关 键 词：高血糖 非酒精性脂肪性肝炎 大鼠 肝脏超微结构 细胞凋亡 

分 类 号：R-33[医药卫生] R446.1