抵抗素在非酒精性脂肪肝大鼠胰岛素抵抗中的作用  

Role of resistin in insulin-resistance of rats with nonalcoholic fatty liver disease

作　　者：朱良荣[1] 管小琴[1] 祁明美[1] 王立娟[1] 

机构地区：[1]重庆医科大学分子医学与肿瘤研究中心病理教研室,重庆400016

出　　处：《中国生物制品学杂志》2012年第2期185-189,共5页Chinese Journal of Biologicals

基　　金：重庆市教委科学技术研究资助项目(KJ090327)

摘　　要：目的探讨抵抗素(Resistin)在非酒精性脂肪肝(Nonalcoholic fatty liver disease,NAFLD)大鼠胰岛素抵抗(Insulinresistance,IR)中的作用。方法采用改良高脂饲料喂养大鼠建立NAFLD IR大鼠模型,以基础饲料喂养的大鼠作为对照组。分别于开始造模后6、8、10周分别采集2组大鼠血清及肝脏组织,测定血清中甘油三酯(TG)、总胆固醇(TC)、丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、空腹血糖(Fasting plasma glucose,FPG)和空腹胰岛素(Fasting insulin,FINS)含量,并计算胰岛素敏感性指数(Insulin sensitivity index,ISI);HE染色观察肝脏病理学改变;RT-PCR和Western blot检测肝组织中胰岛素受体底物-2(Insulin receptor substrate-2,IRS-2)、抵抗素(Resistin)和核因子(NF-κB)基因的mRNA转录水平和蛋白的表达水平,并进行相关性分析。结果改良高脂饲料喂养的大鼠一般状况发生改变,显示模型复制成功;TG、TC、ALT和AST值的测定及肝组织学检查证实模型组大鼠存在高血脂和肝功损害,且有IR的现象存在;与对照组比较,模型组Resistin和NF-κB的mRNA转录水平和蛋白表达水平均明显增高,且呈时间依赖性(P<0.05),Resistin与NF-κB的表达呈正相关;IRS-2的mRNA转录水平和蛋白表达水平逐渐下降,且呈时间依赖性(P<0.05),与Resistin的表达呈负相关。结论 NAFLD中IR的发生可能与胰岛素信号通路有关,涉及其始动因素IRS-2的减少和Resistin的增加。Resistin不仅能抑制IRS的磷酸化而影响胰岛素上游信号的正常传导,还可能通过激活NF-κB抑制其下游通路的传导,而加重IR反应。Objective To investigate the role of resistin in insulin-resistance （IR） of rats with nonalcoholic fatty liver disease （NAFLD）. Methods Rat model of NAFLI） caused by IR was established by feeding with modified high fat diet, using those with basal forage as control. The serum and liver tissue samples were collected 6, 8 and 10 weeks after establishment of model and determined for triglyeride （TG）, total cholesterol （TC）, alanine amiontrasnferase （ALT）, aspartata aminotransferase （AST） fasting plasma glucose （FPG） and fasting insulin（FINS） contents in sera, based on which the insulin sensitivity index （ISI） was calculated. The pathological change of liver was observed by HE staining. The mRNA transcription and protein expression levels of insulin receptor substrate-2 （IRS-2）, resistin and NF-KB in liver tissue were determined by RT-PCR and Western blot respectively, of which the relationship was analyzed. Results The change of general status of rats indicated that the NAFLD model was successfully established. The determination results of TG, TC, ALT and AST and pathological examination of liver proved hyperlipemia, liver function lesion and IR in model rats. Both the mRNA transcription and protein expression levels of either resistin or NF-KB in model group increased significantly as compared with those in control group （P 〈 0. 05）, in a time-dependent mode. However, both the mRNA transcription and protein expression levels of IRS-2 decreased gradually as compared with those in control （P 〈 0. 05）, in a time-dependent mode. The expression of resistin was positively related to that of NF-KB, while was negatively related to that of IRS-2. Conclusion The onset of IR in NAFLD might be associated with insulin signaling pathway, involving the decrease of IRS-2 and increase of resistin. Resistin not only influenced the normal signal transduction of insulin upstream pathway by inhibiting the phosphorylation of IRS, but also increased the severity of IR by activating NF

关 键 词：脂肪肝 抵抗素 胰岛素信号通路 胰岛素受体底物-2 胰岛素抵抗 

分 类 号：R575.5[医药卫生—消化系统]