肝组织胰岛素受体底物1表达及其酪氨酸磷酸化与慢性乙型肝炎病毒感染者胰岛素抵抗的关系  

Assessment of the relationship between expression of insulin receptor substrate-1 (IRS-1) and tyrosine phosphorylation and insulin resistance in hepatic tissue of patients with chronic hepatitis B virus infection

作　　者：戴福宏[1] 曾维琼[1] 江萃英 

机构地区：[1]重庆医科大学附属第二医院感染科,重庆400010 [2]重庆市南川区人民医院感染科,重庆408400

出　　处：《中国现代医学杂志》2012年第29期66-70,共5页China Journal of Modern Medicine

基　　金：重庆市卫生局医学科学技术研究项目(No:2009-2-202)

摘　　要：目的研究慢性乙型肝炎病毒(hepatitis B virus,HBV)感染者肝脏组织中胰岛素受体底物1(insulinreceptor substste-1,IRS-1)表达及其酪氨酸磷酸化与胰岛素抵抗(insulin resistance,IR)的关系。方法共收集36例肝组织,其中来源于健康对照受试者12例,轻度慢性乙型肝炎(mild chronic hepatitis B,MCHB)未合并IR受试者12例,MCHB合并IR受试者12例。测量受试者的空腹血糖(fasting blood glucose,FBG)、空腹血胰岛素(fasting blood insulin,FINS)水平、HBV DNA及乙肝病毒标记物。根据稳态模型计算的胰岛素抵抗指数(homeostasis model assessment,HOMA-IR)界定IR。当HOMA-IR值>2.7定义为IR。采用蛋白质免疫印迹法(Western blotting)检测各组IRS-1蛋白表达及酪氨酸磷酸化水平。结果①MCHB伴IR组FINS、FBG、HOMA-IR、HBV DNA及HBeAg阳性率分别为(19.48±7.97)μU/mL、(5.20±0.62)mmol/L、(4.37±1.34)%、(5.01±1.33)%和75.00%;MCHB未伴IR组FINS、FBG、HOMA-IR、HBV DNA及HBeAg阳性率分别为(8.49±2.78)μU/mL、(5.05±0.54)mmol/L、(1.86±0.58)%、(4.89±1.52)%和58.33%;正常对照组FINS、FBG及HOMA-IR分别为(7.21±2.71)μU/mL、(4.98±0.36)mmol/L和(1.60±0.63)%。MCHB伴IR组的FINS水平和HOMA-IR值显著高于MCHB未伴IR组和正常对照组,差异有统计学意义(P<0.01);HBeAg阳性率及HBV DNA载量差异无统计学意义(P>0.05)。②MCHB伴IR组肝组织IRS-1蛋白表达水平为(0.33±0.03),明显低于正常对照组(0.68±0.03)和MCHB未伴IR组(0.64±0.01),差异具有统计学意义(P<0.01)。③MCHB伴IR组肝组织IRS-1蛋白酪氨酸磷酸化程度为(0.17±0.02),明显低于正常对照组(0.56±0.03)和MCHB未伴IR组(0.53±0.01),差异具有统计学意义(P<0.01)。结论 HBV在胰岛素抵抗中的作用尚未明确。肝脏组织中IRS-1蛋白表达及其酪氨酸磷酸化程度降低,可能是HBV感染者发生胰岛素抵抗的分子机制之一。【Objective】 To study the relationship between expression of insulin receptor substrate-1（IRS1） and tyrosine phosphorylation and insulin resistance in hepatic tissue of patients with chronic hepatitis B virus（HBV） infection.【Methods】 Twenty four mild chronic hepatitis B patients（MCHB） were included,and twelve subjects with normal liver function were served as normal control.IR was determined by the homeostasis model assessment（HOMA-IR）.The group MCHB further divided into group with IR（level of HOMA-IR was greater than 2.7） and group without IR（level of HOMA-IR was less than 2.7）.Levels of fasting blood glucose（FBG）,fasting blood insulin（FINS） and HBV DNA were measured.The protein expression and tyrosine phosphorylation of IRS-1 in hepatic tissue were detected by Western blotting.【Results】①The levels of FINS and HOMA-IR were 19.48±7.97（uU/mL） and 4.37±1.34 in the MCHB with IR group,and were significantly higher than those in the MCHB without IR [8.49±2.78（uU/mL） and 1.86± 0.58;P〈0.01] and in the normal control [7.21 ±2.71（uU/Ml） and 1.60 ±0.63;P〈0.01].The differences of values of FBG [5.20±0.62（mmol/L） in the MCHB with IR group,5.05±0.54（mmol/L） in the MCHB without IR group and 4.98±0.36（mmol/L） in the normal control ]were not significance difference in the three groups.There was not significantly differences in the levels of HBV DNA and the rate of positive HBeAg between MCHB with IR and without IR（5.01±1.33 vs 4.89±1.52,P〈0.05;75.00% vs 58.33%,P〈0.05）.②The protein expression（0.33±0.03） of IRS-1 in hepatic tissue of the MCHB with IR group were significantly decreased compared with those of the normal control group（0.68±0.03,P0.01） and the MCHB without IR group（0.64± 0.01,P〈0.01）.③The tyrosine phosphorylation expression（0.17±0.02） of IRS-1 in hepatic tissue of the MCHB with IR group were significantly declined compared with those of the normal control group（0.56 ±0.03,P〈0.01） and the MCHB wi

关 键 词：乙型肝炎病毒 胰岛素抵抗 胰岛素受体底物1 酪氨酸磷酸化 

分 类 号：R512.62[医药卫生—内科学]