糖尿病大鼠肝脏损伤与胆固醇调节元件结合蛋白-1c及蛋白激酶表达的相关性  

Correlation of liver lesion with the expressions of SREBP-1c and JNK in the rats with diabetic mellitus

作　　者：刘晓丽[1] 陈佳[1] 吴玉婷[1] 徐利芬[1] 孟青[1] 黄崧凇[1] 

机构地区：[1]贵阳医学院附属医院病理科,550004

出　　处：《中华老年医学杂志》2012年第2期161-166,共6页Chinese Journal of Geriatrics

基　　金：贵州省省长基金[黔省专合字（2009）41号]

摘　　要：目的 动态研究2型糖尿病大鼠肝脏脂质代谢紊乱所致的损伤和细胞凋亡及其与固醇调节组件结合蛋白-1c（SREBP-1c）及C Jun氨基端激酶（JNK）表达的关系. 方法 试验大鼠分为4组：（1）糖尿病组,64只,用高糖高脂饲料喂养,予链脲佐菌素（STZ）30 mg/kg个次性腹腔注射复制糖尿病模型；（2）正常对照组,37只,饲以普通饲料,腹腔注射柠檬酸盐缓冲液；（3）STZ组,42只,饲以普通饲料,腹腔注射STZ;（4）高糖高脂组,37只,饲以高糖高脂饲料,腹腔注射柠檬酸盐缓冲液.在不同阶段抽样检查动物体质量、肝质量、空腹血糖、空腹胰岛素（FINS）、三酰甘油（TG）、总胆固醇（TC）、谷丙转氨酶（ALT）、谷草转氨酶（AST）；观察肝脏病理组织学变化及超微结构变化；用实时荧光定量PCR技术检测SREBP-1c、JNK蛋白及mRNA的表达；用流式细胞术检测肝脏细胞凋亡.比较不同组间的差异. 结果（1）糖尿病组大鼠体质量比正常对照组、STZ组、高糖高脂组明显下降（P＜0.05）,肝质量则明显上升（P＜0.05）；糖尿病组大鼠空腹血糖、FINS、TG、TC、ALT、AST亦明显升高（P＜0.05）.光镜下见肝细胞脂肪变性、炎性细胞浸润,网状纤维增多；电镜显示细胞器结构紊乱,随着病程延长病变逐渐加重,肝细胞凋亡增高；SREBP-1c、JNK蛋白及mRNA的表达增高.（2）高糖高脂组亦呈类似的肝脏病变及SREBP-1c、JNK蛋白及mRNA的表达增高的改变,但程度较轻. 结论 胰岛素抵抗和高血糖可导致糖尿病肝脏病变；2型糖尿病、SREBP-1c、JNK表达升高参与了肝脏脂质代谢紊乱与细胞凋亡.Objective To study the dynamic changes of injury and apoptosis of liver induced by lipid metabolic disturbance in the rats with diabetes mellitus and their correlation with the expressions of sterol regulatory element binding protein-1c（SREBP-1c）and c-Jun N-terminal kinase（JNK）.Methods Experimental animals were randomly divided into 4 groups：diabetesgroup（n=64）induced by high-carbohydrate and high-fat diet plus intra-peritoneal streptozeotocin（STZ）injection,normal control（n=37）fed regular diet and receiving citric buffer solution injection,STZ group（n=42）fed regular diet and receiving STZ injection,high gluaxeard fat group（n =37）receiving citric buffer solution injection.Body weight,liver weight,fasting plasma glucose（FPG）,fasting insulin（FINS）,triglyceride（TG）,total cholesterole（TC）,alanine transaminase（ALT）,asparate transaminase（AST）were detected at various time intervals.The changes of liver histopathology and ultrastructure were observed by ES and Sudan Ⅲ stanings,transmission electrom microscope.The expressions of SREBP-1c and JNK mRNAs and proteins were determined by real time-PCR methods.Apoptosis was analyzed by flow cytometry.Results The diabetic rats showed much lower body weight（P〈0.05）and higher liver weight than controls,STZ group and high-carbohydrate and fat group（P〈0.05）,while showed higher levels（P〈0.05）of serum FPG,FINS,TG,TC,ALT,AST.Diabetic rats exhibited fatty degeneration of liver cells accompanied by inflammatory infiltration and fibrosis.Organelle structures were more disturbed and apoptosis was more obviou along with longer course of disease.The expressions of SREBP-1c,JNK proteins and mRNA were significantly enhanced.The rats fed high-carbohydrate and fat diet also showed similar liver lesions and enhanced SREBP-1c,J NK proteins and mRNA expressions but not as severe as in diabetes group Conclusions Insulin resistance and high blood glucose may induce diabetic hepatopathy.The high expressions of JNK and SREBP-1c ma

关 键 词：糖尿病 实验性 肝炎 细胞凋亡 胆固醇调节元件结合蛋白质 蛋白激酶类 

分 类 号：R587.1[医药卫生—内分泌]