摘要目的 观察运动对胰岛素抵抗小鼠骨骼肌过氧化物酶体增殖物激活受体-α(PPAR-α)及靶基因脂酰辅酶A氧化酶(ACO)、烯酰辅酶A水解酶/L-3羟-CoA脱氢酶(EHHADH)mRNA表达的影响,并初步探讨运动改善脂代谢的可能机制.方法 将20只雄性ApoE基因敲除小鼠随机分为高脂组及运动组,高脂组小鼠给予高脂饮食喂养,运动组小鼠在高脂饮食基础上增加游泳训练,另选取C57BL/6J小鼠作为对照组.经干预12周后,测定各组小鼠空腹血脂、血糖及胰岛素浓度,并计算胰岛素抵抗指数;同时取各组小鼠腓肠肌进行电镜超微结构观察,采用RT-PCR方法检测各组小鼠骨骼肌中PPAR-α、ACO及EHHADH mRNA水平.结果 通过电镜观察发现,高脂组可见肌细胞线粒体水肿、肌膜下水肿、肌原纤维间水肿,伴有肌溶解灶,该组小鼠血脂(总胆固醇、低密度脂蛋白、游离脂肪酸)、空腹血糖、空腹胰岛素及胰岛素抵抗指数均较对照组明显升高(均P ＜0.05),骨骼肌中PPAR-α、ACO及EHHADH mRNA表达均较对照组明显下调(均P＜0.05).运动组小鼠经游泳干预后,发现其肌细胞肌原纤维间有轻度水肿,肌纤维排列整齐,未见肌溶解及肌膜下水肿;血脂水平较高脂组明显降低(均P＜0.05),高密度脂蛋白较高脂组明显升高(P＜0.05);空腹血糖、空腹胰岛素及胰岛素抵抗指数较高脂组明显降低(均P＜0.05),骨骼肌中PPAR-α、ACO及EHHADH mRNA表达较高脂组明显上调(均P＜0.05).结论 游泳运动可显著改善ApoE基因敲除小鼠脂代谢紊乱及胰岛素抵抗,其治疗机制可能与上调骨骼肌中PPAR-α,进一步激活其下游靶基因ACO及EHHADH,从而提高脂肪酸氧化代谢能力有关.

abstractsObjective To observe the influence of exercises on the mRNA expression of peroxisome proliferator-activated receptor (PPAR-α) and its target genes of acyl-CoA oxidase (ACO),Enoyl-CoA-hydratase and 3-hydroxyacyl-CoA-dehydrogenase (EHHADH) in the skeletal muscles in insulin-resistance mice to develop a way to improve the lipid metabolism.Methods Twenty male ApoE knockout mice were randomly divided into two groups,the high-fat diet group (group HFD) and the exercise training group (group Ex).The HFD group were fed with highfat diet,while the Ex group were fed in the same way,with additionally swimming training.And ten healthy male C57BL/6j mice were chosen as the control group(group ND).After 12 weeks of intervention,the serum lipid,blood glucose and insulin levels were determined,and homeostasis model assessment insulin resistance index (Homa-IRI) was calculated.The bilateral gastrocnemiuses were cut to be observed under a transmission electron microscope,and the mRNA expression of PPAR-α,ACO and EHHADH in skeletal muscle were measured using reverse transcription polymerase chain reaction(RT-PCR).Results The transmission electron microscope showed that the sarcolemma edema,mitochondrial swelling,as well as focal myocytolysis and edema within myofibrils were observed in the HFD group.The total cholesterol,low-density lipoprotein cholesterol,free fatty acid,fasting glucose,insulin and HomaIRI of the HFD group were significantly higher than the control group (P ＜ 0.05),while the mRNA expression of PPAR-α,ACO and EHHADH was significantly deceased than the latter(P ＜ 0.05).After swimming,the abovementioned pathological changes disappeared.The serum lipid of the Ex group were significantly lower (P ＜ 0.05),while HDL was significantly higher (P ＜ 0.05).And fasting insulin,glucose and HOMA-IR of the Ex group were significantly lower (P ＜ 0.05),while the mRNA expression of the above in the Ex group were significantly increased (P ＜0.05).Conclusion Swimming training could improve insulin resistance and metabolic disorder of lipid of ApoE knockout mice.The possible mechanisms may be through up-regulating the expression of PPAR-α,which in turn stimulates the expression of ACO and EHHADH mRNA to strengthen fatty acid β-oxidation.