8周游泳运动对2型糖尿病大鼠海马胰岛素抵抗的影响及机制

Effect of 8-Week Swimming Exercise on Insulin Resistance in Hippocampus of Type 2 Diabetic Rats and Its Mechanism

目的探讨糖尿病大鼠海马胰岛素抵抗的发生发展及在运动干预下糖尿病海马胰岛素抵抗与半乳糖苷凝集素3以及脂联素/AMPK/GLUT4信号通路之间的关系。方法高脂饮食联合腹腔注射低剂量STZ诱导的2型糖尿病大鼠建模成功后随机分为糖尿病对照组(DM组)和糖尿病运动组(DME组)两组。DM组大鼠不运动,DME组进行8周无负重游泳训练,6次/周。大鼠于末次训练后禁食12h,次日以2.5ml/kg的剂量,腹腔注射10%的水合氯醛麻醉,随后胸主动脉取血后保存于-20℃,以备待测,取海马组织投入液氮,-80℃冰箱保存。结果1)与NC组相比,DM组大鼠血清FBG、HOMA-IR的含量显著性增加(p<0.01),而大鼠血清INS含量减少,但无显著性差异(p>0.05);与DM组相比,DME组大鼠血清FBG、HOMA-IR的含量显著性减少(p<0.05),而大鼠血清INS含量减少,但无显著性差异(p>0.05);2)Real-Time PCR结果显示:与NC组相比,DM组大鼠GLUT4、PI3K及Adiponectin(脂联素)mRNA表达水平显著降低(p<0.01),Galectin-3、IRS-1mRNA表达水平显著升高(p<0.05,p<0.01),尽管AMPK、AKtmRNA表达水平无显著性变化,但存在有明显的下降趋势;与DM组相比,DME组大鼠海马组织的Galectin-3mRNA表达水平显著降低(p<0.05),PI3K、GLUT4及Adiponectin mRNA表达水平呈显著增加(p<0.01),AMPK、IRS-1及AKt mRNA表达水平无显著性变化,但仍存在改善趋势。结论1)2型糖尿病将导致病理性中枢胰岛素抵抗,同时8周有氧运动能够有效改善2型糖尿病海马胰岛素抵抗;2)8周有氧运动可能通过降低海马组织Gal-3水平以及提高脂联素/AMPK/GLUT4信号通路表达,从而达到改善2型糖尿病海马胰岛素抵抗,同时Gal-3以及脂联素/AMPK/GLUT4信号通路异常可能也是2型糖尿病病理性引发中枢胰岛素抵抗的机制之一。

Objective To investigate the development of hippocampal insulin resistance in diabetic rats and its relationship with galectin-3 and adiponectin/AMPK/GLUT4 signaling pathways under exercise intervention.Methods Male SD rats were randomly divided into control group(NC group)and diabetic model group(DM group)with high-fat diet.After 5 weeks of high-fat diet feeding,the DM group was injected with 1%STZ at the dose of 40 mg/kg.One week later,blood samples were collected from the tail vein of rats,and the fasting blood glucose was more than 7.8mmol/L,which indicated that the model was successful.After successful modeling,normal diet was restored.The rats were randomly divided into two groups:diabetic control group(DM group)and diabetic exercise group(DME group).In DME group,swimming training without load was carried out every day,6 days a week and 60min each time for 8 weeks.After the last training,the rats were fasted for 12 hours.The next day,the rats were anesthetized by intr aperitoneal injection of 10%chloral hydrate at the dose of 2.5 ml/kg.Then the blood samples of thoracic aorta were stored at-20℃for testing.The hippocampal tissues were taken and stored in-80℃refrigerator.Results 1)compared with NC group,the contents of FBG and HOMA-IR in DM group were significantly increased(p<0.01),while the contents of INS in serum were decreased,but there was no significant difference(p>0.05);compared with DM group,the contents of FBG and HOMA-IR in DME group were significantly decreased(p<0.05),while the contents of INS in serum of rats were decreased,but there was no significant difference(p>0.05);2)real time The results of PCR showed that compared with NC group,the mRNA expression levels of GLUT4,PI3K and adiponectin in DM group were significantly decreased(p<0.01),while the mRNA expression levels of galectin-3 and IRS-1 were significantly increased(p<0.05);Compared with DM group,the expression of galectin-3 mRNA in hippocampus of DME group was significantly decreased(p<0.05),the mRNA expression of PI3K,GLUT4 and adiponectin was significantly increased(p<0.01),AMPK,IRS-1 and Akt were significantly increased(p<0.01)There was no significant change in mRNA expression,but there was still a trend of improvement.Conclusion 1)Type 2 diabetes mellitus will lead to pathological central insulin resistance,and 8-week aerobic exercise can effectively improve insulin resistance in hippocampus of type 2 diabetes mellitus.2)8-week aerobic exercise may improve hippocampal insulin resistance in type 2 diabetes mellitus by reducing the level of Gal-3 and increasing the expression of adiponectin/AMPK/GLUT4 signaling pathway.Meanwhile,abnormal Gal-3 and adiponectin/AMPK/GLUT4 signaling pathway may also be one of the mechanisms of central insulin resistance induced by type 2 diabetes.