抵抗素在非酒精性脂肪肝病中对胰岛素抵抗和肝纤维化的作用  

Role of resistin in the development of insulin resistance and hepatic fibrosis in nonalcoholic fatty liver disease

作　　者：祁明美[1] 管小琴[1] 朱良荣[1] 杨云鹏[1] 

机构地区：[1]重庆医科大学病理教研室,重庆市400016

出　　处：《世界华人消化杂志》2012年第16期1383-1388,共6页World Chinese Journal of Digestology

基　　金：重庆市教委基金资助项目;No.KJ090327~~

摘　　要：目的:探讨抵抗素(resistin)在非酒精性脂肪肝病(non-alcoholic fatty liver disease,NAFLD)中对胰岛素抵抗(insulin resistin,IR)及肝纤维化的作用.方法:应用高脂饮食喂养Wistar大鼠建立NAFLD肝纤维化模型.健康♂,Wistar大鼠30只,随机分成正常对照组和模型组,各15只,分别给予普通饲料和高脂饲料喂养.分别于第15、18、21周末将对照组和模型组随机各处理5只.检测空腹血糖(FBG)、空腹胰岛素(FINS)、Ⅲ型前胶原(PCⅢ)、透明质酸(HA)、Ⅳ型胶原(CⅣ)、层粘蛋白(LN)水平,采用稳态模型评估法(HOMA)评估IR(HOMA-IR);HE、VG染色及电镜观察肝组织纤维化情况.RT-PCR法检测大鼠肝组织中resistin基因mRNA表达.结果:随着高脂喂养时间的延长,HE、VG染色及电镜观察肝组织病理学显示大鼠肝脏脂肪变性及肝纤维化程度逐渐加重,NAFLD模型组HOMA-IR、PCⅢ、LN、CⅣ、HA、resistin逐渐增加,且以21wk时升高最为明显,分别为33.74g/L±10.41g/L、2.96g/L±0.76g/L、4.14g/L±1.07g/L、19.07g/L±2.78g/L、848.87g/L±204.04g/L、0.99g/L±0.10g/L,与相应时相对照组比较差异具有统计学意义(P<0.05或P<0.01).Spearman相关性分析抵抗素与HOMA-IR、PCⅢ、LN、CⅣ、HA呈显著正相关,相关系数r分别为0.77、0.80、0.68、0.67、0.76(P<0.05或P<0.01).结论:在NAFLD纤维化形成过程中,抵抗素表达升高诱导IR并促使肝纤维化的形成与进展.AIM： To investigate the role of resistin in the development of insulin resistin （IR） and hepatic fibrosis in nonalcoholic fatty liver disease （NAFLD）. METHODS： Thirty male Wistar rats were randomly divided into control group （n = 15） and model group （n = 15）. The control group was fed a normal diet, while the model group was given a high fat diet to induce NAFLD. Five rats in each group were killed at 15, 18 and 21 wk. Serum levels of FBG, FINS, type Ⅲ procollagen （PC Ⅲ）, hyaluronic acid （HA）, type Ⅳ collagen （C Ⅳ） and laminin （LN） were measured. Insulin resistance was calculated by homeostasis model assessment （HOMA-IR）. Liver tissue samples were collected and the degree of hepatic fibrosis was graded by hematoxylin-eosin （HE） staining, VG staining and electron microscopy. RT-PCR was used to determine the expression level of resistin mRNA. RESULTS： The degree of hepatic fibrosis increased with the time of feeding the high fat diet. Compared to the control group, the levels of HOMA-IR, PC Ⅲ, LN, C Ⅳ, HA and resistin significantly increased, which was particularly prominent at week 21 （33.74 g/L ± 10.41 g/L, 2.96 g/L ± 0.76 g/L, 4.14 g/L ± 1.07 g/L, 19.07 g/L ± 2.78 g/L, 848.87 g/L ± 204.04 g/L, 0.99 g/L ± 0.10 g/L, all P 〈 0.05 or 0.01）. Re- sistin expression was positively correlated with the levels of HOMA-IR, PCIII, LN, C Ⅳ, and HA （r = 0.77, 0.80, 0.68, 0.67, 0.76, all P 〈 0.05 or 0.01）. CONCLUSION： Resistin may induce IR and promote the formation of hepatic fibrosis in NAFLD.

关 键 词：抵抗素 肝纤维化 非酒精性脂肪肝病 胰岛素抵抗 

分 类 号：R575.5[医药卫生—消化系统]