有氧运动加谷氨酰胺补充对2型糖尿病大鼠骨骼肌炎症因子NF-κB、MPO及MCP-1基因表达的影响

Effect of Aerobic Exercise plus Glutamine Supplement on Expression of Muscle NF-κB,MPO and MCP-1 mRNA of Type 2 Diabetes

目的:观察长期有氧运动联合谷氨酰胺(Gln)补充对2型糖尿病(T2DM)大鼠骨骼肌炎症因子核转录因子-κB(NF-κB)、单核细胞趋化蛋白-1(MCP-1)、髓过氧化物酶(MPO)基因表达及空腹血糖(FBG)、血胰岛素(ISN)及胰高血糖素样肽-1(GLP-1)的影响。方法:将雄性Sprague-Dawley大鼠60只(179.8±19.2g)随机分为健康对照组(C组,26只)和糖尿病造模组(D组,34只)。对照组普通饲料喂养,糖尿病组高脂喂养。4周后糖尿病组大鼠腹腔注射35mg/kg链脲佐菌素诱导T2DM。成模后两组进一步随机分为:安静组(CQ,DQ)、运动组(CE,DE)、Gln组(CG,DG)、运动加Gln组(CEG,DEG)。运动组大鼠进行6周游泳运动。Gln组改用含2%(w/w)L-Gln饲料喂养。腹主动脉取血测FBG、ISN及GLP-1水平,腓肠肌测NF-κB、MPO及MCP-1的mRNA的表达。结果:安静状态下T2DM大鼠(DQ)骨骼肌NF-κB、MCP-1及MPO的mRNA表达量及血FBG值显著高于对照组(CQ),血ISN和GLP-1水平明显低于对照组。6周游泳运动(DE)或Gln补充(DG)可明显降低T2DM大鼠骨骼肌NF-κB、MCP-1及MPO的mRNA表达和血FBG水平,并增加ISN及GLP-1水平。6周游泳运动联合Gln补充(DEG)时,降低T2DM大鼠骨骼肌NF-κB mRNA表达的效应显著高于单纯Gln补充组(DG),但与单纯运动组(DE)相似;对MCP-1mRNA的抑制与单纯Gln补充组(DG)相似,但明显高于单纯运动组(DE);对MPO mRNA表达的影响与单纯运动组(DE)或单纯Gln补充组(DG)相似;降低FBG水平、增加GLP-1的作用较单纯运动组(DE)或Gln补充组(DG)明显,增加ISN的效应与单纯运动组(DE)或Gln补充组(DG)相似。结论:长期有氧运动或Gln补充明显抑制T2DM大鼠骨骼肌炎症因子NF-κB、MPO及MCP-1的基因表达,增加GLP-1及ISN的分泌量,降低FBG值。当运动联合Gln补充时,降低T2DM骨骼肌炎症因子产生、升高GLP-1及降低FBG的效应较运动或Gln单因素作用时明显,对ISN分泌的影响与单纯运动或Gln补充相似。

Objective：To investigate the effects of aerobic exercise or/and glutamine （Gin） supplement on expression of muscle nuclear factor-;B （NF-;B）, myeloperoxidase （MPO） and monoeyte chemotactic protein-1 （MCP-1） mRNA, as well as serum level of fasting blood-glucose （FBG）, insulin （ISN） and of glucagon-like peptide 1 （GLP-1） of Type 2 Diabetes Mellitus（T2DM）. Methods.. Sixty male Sprague-Dawley （SD）rats （179. 8±19. 2 g） were randomly divided into control group （C, n= 26） and diabetic group （D, n=34）. After 4 weeks of regular diet or high fat diet respectively, the rats in the diabetic group were injected intraperitoneally with streptozotocin （35 mg/kg） to induce the T2DM model, as soon as the model was induced, the rats in each group were further divided into 4 groups： quiet group （CQ, DQ）, exercise group （CE, DE）, Gln group （CG, DG）, exercise plus Gln group （CEG, DEG）. The rats in exercise groups performed swimming for 6 weeks, in Gin groups fed with 2; （w/w） L- Gln for 6 weeks. Abdominal aorta blood was harvested for testing FBG, ISN and GLP-1, gastrocnemius muscle for muscle NF-κB, MPO and MCP-1 mRNA. Results： T2DM rats without exercise（DQ） had more expression of NF-κB, MCP-1 and MPO mRNA, higher FBG and lower INS and GLP-1 than control group（CQ）. 6 weeks swimming （DE） or Gln supplement （DG） obviously decreased NF-κB, MCP-1 and MPO mRNA and FBG level and increased ISN and GLP-1 in T2DM rats. Effect of swimming plus Gln supplement（DEG） showed more suppression on NF-κB mRNA expression of T2DM than the sole Gln supplement （DG）, and similar to the sole exercise （DE）; on MCP-1 mRNA showed similar effects as sole Gln supplement （DG）, but stronger than sole exercise （DE） ;on MPO mRNA showed similar effects as either sole exercise（DE） or sole Gin supplement （I;） ; on FI; and GLP-1 showed effects more than either sole exercise（DE） or sole Gln supplement（DG）, on ISN showed similar effects as sole exercise（DE） or sole Gln supplement （DG） . Conclusion： Chronic aerobic exercise or Gln supplement obviously reduced expression of NF-κB, MPO and MCP-1 mRNA and FBG level, increased GLP-1 and ISN level of T2DM. Combination of swimming and Gln supplement showed stronger effects on decreasing inflammatory cytokines and FBG, increasing GLP-1 of T2DM than either sole swimming or sole Gln supplement, but on ISN the combination showed no more effects.