细胞信号转导抑制因子在宫内发育迟缓大鼠骨骼肌细胞中的表达及意义

Expression of Suppressor of Cytokine Signaling in Skeletal Muscle Cell of Intrauterine Growth Restriction Rats and Its Significance

目的研究宫内发育迟缓(IUGR)大鼠骨骼肌细胞中细胞信号转导抑制因子(SOCS)及胰岛素信号通路重要分子胰岛素受体底物-1(IRS-1)的表达变化。探讨其在IUGR大鼠成年后胰岛素抵抗发生中的机制及意义。方法用孕期限制饮食法建立大鼠IUGR模型,原代培养大鼠骨骼肌细胞,采用Real time PCR和Western blot检测0周和12周龄IUGR子鼠骨骼肌细胞中SOCS-1、SOCS-3及IRS-1的mRNA和蛋白表达。采用SPSS17.0软件进行统计学分析。结果与对照组相比,0周和12周龄IUGR组子鼠中骨骼肌细胞中SOCS-1、SOCS-3的mRNA和蛋白表达水平均增加(Pa<0.05),而IRS-1的mRNA和蛋白表达水平均下降(Pa<0.05)。IRS-1mRNA与SOCS-1 mRNA、SOCS-3 mRNA表达水平均呈负相关(r=-0.832、-0.789,Pa<0.01)。结论 IUGR大鼠子代骨骼肌细胞SOCS-1、SOCS-3表达增加,通过负性调节使得IRS-1表达降低,可能是骨骼肌胰岛素抵抗和成年代谢综合征发生的机制之一,提示SOCS-1和SOCS-3可以作为2型糖尿病和其他胰岛素抵抗的治疗靶点。

Objective To investigate the change of the expression of suppressor of cytokine signaling（SOCS） ,and insulin receptor substrate - 1 （IRS- 1 ） which is important in insulin signaling pathway in skeletal muscle cell of intrauterine growth restriction （IUGR） rats, in order to explore the effect on the incidence of insulin resistance in adult IUGR rats. Methods IUGR animal models were established by maternal nu- trition restriction. Get skeletal muscle cells by primary cuhure. The levels of SOCS - 1 ,SOCS -3 and IRS - 1 in skeletal muscle cells of new- born and 12 - week IUGR rats were detected by real time PCR and Western blot. SPSS 17.0 software was used to analyze the data. Results The mRNA and protein expression levels of SOCS - 1 ,SOCS - 3 were higher than those in control group（P 〈 0.05）. The mRNA and protein expression level of IRS - 1 were lower than those in control group（ P 〈 0.05 ）. The amount of IRS - 1 mRNA expression were negatively correla- ted with the mRNA expression of SOCS - 1 and SOCS - 3 （ r = - 0. 832, - 0. 789,Pa 〈 0.01 ）. Conclusions Increased expression of SOCS - 1, SOCS - 3 contributes to the decreased expression of IRS - 1, which maybe play an important role in insulin resistance in IUGR rats. SOCS - 1 and SOCS -3 may provide new ideas and methods in type 2 diabetes therapy and insulin resistance.