慢性乙型肝炎患者肝组织胰岛素受体底物2的表达及其酪氨酸磷酸化的研究  

Expression of insulin receptor substrate-2 and its tyrosine phosphorylation in the hepatic tissue of chronic hepatitis B patients

作　　者：朱其荣[1] 秦波[1] 黄涛[2] 刘汉屈[1] 

机构地区：[1]重庆医科大学附属第一医院感染科,400016 [2]四川省成都市传染病医院,610091

出　　处：《中国危重病急救医学》2010年第1期24-27,共4页Chinese Critical Care Medicine

摘　　要：目的观察慢性乙型肝炎（cHB）患者肝组织胰岛素受体底物2（IRS-2）的mRNA和蛋白表达及其酪氨酸磷酸化程度，探讨IRS-2在CHB患者胰岛素抵抗（IR）发生中的作用。方法选择6例肝功能正常者（对照组）及18例CHB患者，CHB患者再按HOMA模型计算的胰岛素抵抗指数分为CHB非IR（〈2．69）组（10例）和CHB合并IR（〉2．69）组（8例）。所有患者于术中及肝穿刺后留取肝组织，采用逆转录-聚合酶链反应检测IRS-2mRNA表达；采用蛋白质免疫印迹法检测IRS-2蛋白表达；采用免疫沉淀及增强化学发光法检测IRS-2酪氨酸磷酸化程度。结果CHB非IR组肝组织IRS-2 mRNA（0．38士0．06）、蛋白（0．94±0．18）表达及酪氨酸磷酸化程度（0．78±0．09）较对照组（分别为0．45±0．11、0．99±0．20、1．00±0．23）有所降低，但差异无统计学意义（t0P〉0．05）；CHB合并IR组IRS-2 mRNA（0．26±0．08）、蛋白（0．67±0．11）表达及酪氨酸磷酸化程度（0．63±0．14）均较对照组明显降低，差异有统计学意义（P〈0．05或P〈0．01）。结论CHB合并IR患者肝组织IRS-2的mRNA和蛋白表达及酪氨酸磷酸化程度的降低可能是产生IR的机制之一。Objective To observe the expression of insulin receptor substrate-2 （IRS-2） mRNA and protein, and its tyrosine phosphorylation in hepatic tissue of chronic hepatitis B （CHB） patients, and to explore the role of IRS-2 on insulin resistance in CHB patients. Methods Eighteen patients with CHB were included, and 6 individuals with normal liver function were enrolled as control. Based on the insulin resistance index determined by homeostasis model assessment （HOMA）, CHB patients were further divided into CHB without insulin resistance group （〈2. 69, n= 10） and CHB with insulin resistance group （〉2. 69, n = 8）. Hepatic tissues were harvested from all patients during operation or with liver biopsy. The mRNA expression of IRS-2 in liver tissue was assessed by reverse transcription-polymerase chain reaction （RT-PCR）, and the protein expression of IRS-2 was detected by Western blotting. Immunoprecipitation and enhanced chemiluminescent technique were used to measure the tyrosine phosphorylation of IRS-2. Results In CHB without insulin resistance group, the mRNA expression （0. 38±0.06）, the protein expression （0. 94±0. 18） and the tyrosine phosphorylation （0. 78±0. 09） of IRS-2 in hepatic tissue were decreased, but without statistically significant difference （all P〉0. 05）, as compared to those in control group （0. 45 ± 0. 11, 0. 99±0. 20, 1.00±0.23, respectively）. In CHB with insulin resistance group, the mRNA expression （ 0. 26± 0. 08）, the protein expression （0.67 ± 0. 11） and the tyrosine phosphorylation （0. 63 ± 0.14） of IRS-2 in hepatic tissue were significantly decreased compared with those of the control group with statistically significant difference （P〈0.05 or P〈0. 01）. Conclusion The decreased expression of mRNA and protein and the reduced tyrosine phosphorylation of IRS-2 in CHB patients with insulin resistance inducing impairment of the insulin signal pathway may be one of the mechanisms underlying insulin resistance.

关 键 词：肝炎 乙型 受体 胰岛素 胰岛素受体底物2 胰岛素抵抗 酪氨酸磷酸化 

分 类 号：R512.62[医药卫生—内科学]