细胞因子信号转导抑制因子3在糖尿病大鼠肝脏和骨骼肌中的表达及意义

Expression and role of suppressor of cytokine signaling 3 in liver and skeletal muscle of diabetes lab rats

目的观察糖尿病大鼠肝脏和骨骼肌中细胞因子信号转导抑制因子3(SOCS-3)表达水平的变化,探讨其在胰岛素抵抗发生中的机制。方法将40只雄性SD大鼠随机分为对照组和糖尿病组,每组20只。对照组大鼠予以普通饲料喂养,糖尿病组大鼠予以高糖高脂饲料喂养4周后腹腔注射链脲霉素,其中16只大鼠制成2型糖尿病模型。采用放射免疫法检测大鼠血清胰岛素浓度,葡萄糖氧化酶法检测血清葡萄糖水平,计算胰岛素敏感指数和胰岛素抵抗指数。实时荧光定量PCR法、Western blot法分别检测大鼠肝脏和骨骼肌中SOCS-3的mRNA、蛋白水平。采用t检验及Pearson直线相关分析进行数据分析。结果 1成功建立糖尿病大鼠模型;2糖尿病组大鼠胰岛素、血糖及胰岛素抵抗指数较对照组显著升高(P<0.05),而胰岛素敏感指数明显降低(P<0.05);3糖尿病组大鼠肝脏和骨骼肌SOCS-3 mRNA较对照组明显升高(P<0.05);4糖尿病组大鼠肝脏和骨骼肌SOCS-3蛋白较对照组明显升高(P<0.05);5糖尿病组大鼠肝脏和骨骼肌SOCS-3的mRNA、蛋白表达水平分别与胰岛素含量呈正相关(r=0.813、0.871、0.851、0.874,P<0.05)。结论糖尿病大鼠肝脏和骨骼肌SOCS-3基因表达增加,负性调节胰岛素信号传导通路,可能参与了胰岛素抵抗的发生机制。

Objective To observe the expression of suppressorsofcytokinesignaling3 （ SOCS-3 ） in liver and skeletal muscleofrat model of type 2 diabetes and to investigate its role in the pathogenesis of insulin resistance. Methods Fortymale SD rats were randomly divided into two groups. Thecontrol group（20 malerats） were fed with standard diet, while thediabetesgroup（ 20 malerats）were fed with high sucrose-fat diet for 4 weeks and then injected intraperitoneally with streptozotocin（STZ） , 16 malerats satisfied the case definitionof type-2 diabetes. Thelevel of serum insulin wasmeasured with radioimmunity, the level of glucose wasmeasured withglucose oxidase method, and the insulin sensitivity index and insulin resistance index were calculated. Thelevelsof SOCS-3 mRNA and SOCS-3 protein expression in liver and skeletal musclewere detected by real-time PCR and Western blot. The data were analyzed by T-test and Pearson linear correlation analysis. Results （1）Normal SD rats fed with high sucrose-fat diet for 4 weeks and then injectedintraperitoneally with STZ could establish type-2 diabetes model. （2）Compared withcontrol group, the levelsof serum insulin andglucose, andthe insulin resistance index in diabetes group were increasedsignificantly（P 〈0.05） ,while the insulin sensitivity index was decreased significantly（ P 〈 0.05 ）. （3）The SOCS-3 mRNA and protein expression level of liver and skeletal muscle in the diabetes group were higher than in thecontrol group（P 〈 0. 05 ）. （4）The SOCS-3 protein expression level of liver and skeletal muscle in the diabetes groupwere higher than in the control group（ P 〈 0.05 ）. （5）The SOCS-3 mRNA and protein expression of liver and skeletal musclewere positively correlated with the levelsof serum insulinin diabetes group （r = 0. 813,0. 871, 0. 851,0. 874,P 〈 0.05）. Conclusion The increased expression of SOCS-3 may act as the negative factors of insulin signaling pathway and may play an important role in insulin resistance.