糖尿病非酒精性脂肪肝病大鼠肝组织胰岛素受体、瘦素受体mRNA的表达  

mRNA expression of insulin receptor and leptin receptor in liver of nonalcoholic fatty liver disease from diabetic rats

作　　者：陈三妹[1] 王蓉蓉[2] 牛三强[2] 吴亮[2] 肖艳[2] 陈丽玲[3] 陈国荣[2] 

机构地区：[1]绍兴文理学院医学院,浙江绍兴312000 [2]温州医学院附属第一医院病理科,浙江温州325000 [3]温州医学院附属第一医院检验科,浙江温州325000

出　　处：《中国病理生理杂志》2009年第7期1370-1375,共6页Chinese Journal of Pathophysiology

基　　金：温州医学院重大资助项目(No.XNK05010);浙江省科技计划资助项目(No.2007C34003)

摘　　要：目的:观察2型糖尿病大鼠肝脏的病理变化,探讨肝组织胰岛素受体(insulin R)、瘦素受体(leptin R)mRNA表达在糖尿病性非酒精性脂肪肝病(NAFLD)发病机制中的作用。方法:SD大鼠随机分成2组:正常组与2型糖尿病组。2型糖尿病组在以高脂饮食4周后,加小剂量(30mg/kg)链脲佐菌素(STZ)诱导2型糖尿病性非酒精性脂肪性肝病大鼠模型,继续给予高脂饮食12周。分别采用HE染色、苏丹Ⅲ染色、Masson染色光镜下观察肝脏组织的病理改变;透射电镜观察肝脏超微结构改变;生化法检测血糖、血甘油三酯(TG)、血总胆固醇(TC)、丙氨酸转氨酶(ALT)和天门冬氨酸转氨酶(AST)水平;放免法检测血清胰岛素水平;ELISA法检测血清瘦素水平;RT-PCR法检测肝组织磷酸烯醇式丙酮酸羧激酶(PEPCK)、葡萄糖-6-磷酸酶(G6Pase)、insulin R、leptin R mRNA表达水平。结果:糖尿病大鼠肝细胞明显脂肪变性、碎片状坏死伴炎细胞浸润及肝纤维化病变,电镜下主要表现为肝细胞核固缩,胞浆内含大量脂滴,狄氏间隙胶原纤维增生;血糖、血胰岛素、TG、ALT、AST水平明显升高(P<0.01),TC水平升高(P<0.05),血清瘦素水平明显下降(P<0.01);肝组织insulin R、leptin R mRNA表达显著升高(P<0.01),PEPCK、G6Pase mRNA表达无显著变化。结论:2型糖尿病时的胰岛素抵抗是NAFLD发生的根源,由于胰岛素抵抗而致的低血清瘦素水平、肝组织insulin R、leptin R表达上调参与了NAFLD的发生。AIM ： To observe the pathologic changes of liver in diabetic rats and to investigate the role of mRNA expression of insulin receptor and leptin receptor in the pathogenesis of nonalcoholic fatty liver disease （NAFLD）. METHODS ： Twenty male Sprague - Dawley rats were divided randomly into two groups： normal control group and diabetic group. After fed with high - fat diet for 4 weeks, diabetic rats were injected with streptozotocin at a dosage of 30 mg/kg intraperitoneally to induce NAFLD model of type 2 diabetes mellitus. Then the diabetic animals were fed with high - fat diet continuously for 12 weeks. At the end of the experiment, the rats were sacrificed, the concentrations of blood glucose, serum lipid, ALT and AST were measured biochemically. The levels of serum leptin and serum insulin were detected by enzyme - linked immunosorbent assay （ELISA） and radio immunoassay （ RIA）, respectively. The pathologic changes of liver were observed under light microscopy （LM） stained with HE, Sudan Ⅲ and Masson trichrome staining, respectively. The ultra - structural changes of liver were observed under transmission electron microscopy （TEM）. Additionally, the mRNA expressions of PEPCK, G6Pase, insulin R and leptin R from rat livers were assayed by semi - quantitative RT - PCR. RESULTS ： The levels of blood glucose, serum insulin, serum TG, ALT and AST increased significantly （P 〈 0. 01 ）, serum TC elevated （P 〈0. 05 ）, and the levels of serum leptin decreased （P 〈0. 01 ） in diabetic group compared to those in nor-real control group. Obvious liver fatty degeneration, piecemeal necrosis with accompanying inflammatory infiltration and fibrosis were found under LM. Hepatocytes pyknosis, lots of lipid deposits in cytoplasm of hepatocytes, proliferation of collagen in space of Disse were observed under TEM in diabetic group. The expression of insulin R and leptin R mRNA in liver from diabetic rats increased significantly （ P 〈 0. 01 ） while the expression of PEPCK and G6Pase

关 键 词：糖尿病 脂肪肝 非酒精性 瘦素 受体 瘦素 受体 胰岛素 

分 类 号：R363[医药卫生—病理学]