TRIM72在运动改善胰岛素信号途径PI3-K/Akt中的作用

Role of TRIM72 in Insulin Signaling Pathway PI3-K/Akt Improved by Exercise Intervention

目的:探讨TRIM72在游泳运动改善高脂饮食大鼠IR中的作用。方法:以SD大鼠为实验对象,随机分为4组:普通饮食对照组(C组)、普通饮食运动组(CE组)、高脂饮食IR模型组(H组)、高脂饮食运动组(HE组)。通过8周高脂饲料喂养建立IR大鼠动物模型,同时对大鼠实施无负重游泳运动干预。用正糖钳技术结合胰岛素抵抗指数(HOMA-IR)和胰岛素敏感指数(ISI)评价动物模型的建立;通过观察运动对高脂饮食IR大鼠脂质沉积、骨骼肌氧化应激水平、TRIM72和Akt表达水平的变化,探讨运动干预IR的机制。结果:1)8周高脂饮食喂养后,H组大鼠葡萄糖输注速率(GIR)显著下降(P<0.01),ISI水平显著下降(P<0.01),HOMA-IR水平显著增加(P<0.01),提示胰岛素抵抗大鼠建模成功。2)8周游泳干预后,与H组相比,HE组大鼠GIR显著增加(P<0.01),血清INS含量和HOMA-IR水平均显著降低(P<0.01),ISI水平显著增加(P<0.05或P<0.01);HE组大鼠骨骼肌脂质沉积减少,骨骼肌SOD和GSH-Px活性均显著增加(P<0.05,P<0.01),MDA和8-OH-d G含量均显著减少(P<0.05,P<0.01),骨骼肌TRIM72 mRNA和TRIM72蛋白表达水平均显著下降(P<0.05,P<0.01),骨骼肌p AktSer473磷酸化水平和Akt蛋白表达水平均显著增加(P<0.05,P<0.01),p IRS-1Ser307的磷酸化水平显著下降(P<0.01)。结论:8周游泳运动可以通过抑制氧化应激,减轻骨骼肌细胞受损伤程度,从而降低大鼠骨骼肌TRIM72表达水平,增强骨骼肌PI3-K/Akt信号转导,改善高脂饮食大鼠IR。

Objective： This study aimed at investigating the effects of TRIM72 on improving insulin resistance in high-fat-diet rats through swimming exercise. Methods： SD rats were randomly assigned to 4 groups： 1） sedentary rats fed with normal diet group（ C group）; 2） normal diet rats swimming with 90 min / time（ CE group）; 3） sedentary rats fed with high-fat diet group（ H group）; 4） high-fat diet rats swimming with 90 min / time（ HE group）.Rats of H group were fed with high-fat diet for 8 weeks to induce insulin resistance（ IR）. The animal model was evaluated by insulin resistance index（ HOMA-IR） and insulin sensitivity index（ ISI） combined with Andres clamp technique. The effects of exercise on lipids deposition,skeletal muscle oxidative stress level,TRIM72 and Akt levels in IR rats were observed to detect the mechanism of exercise improve IR. Results： 1） After 8 weeks high-fat diet,the glucose infusion rate（ GIR） and ISI level in H group decreased（ Ps〈0. 01）,and HOMA-IR increased（ P〈0. 01）,which indicated that the animal model of IR was established successfully. 2） Compared with H group,the GIR and ISI levels in HE group increased（ Ps〈 0. 05） after 8 weeks,and INS content and HOMA-IR decreased（ P〈0. 01）; in HR group,the lipid deposition decreased while SOD and GSH-Px activity in skeletal muscle increased（ Ps〈0. 05）,and the MDA,8-OH-d G,TRIM72 mRNA and protein level and p IRS-1Ser307 phosphorylation level decreased（ Ps〈0. 05）,p Akt Ser473 phosphorylation level and Akt expression increases（ Ps〈0. 05）. Conclusion： Eight weeks swimming can alleviate the damage degree of skeletal muscle cells by inhabiting oxidative stress; it can reduce TRIM72 level and enhance the signal transduction of PI3-K / Akt in skeletal muscle,and improve IR of high-fat diet rats.