运动对ApoE基因敲除小鼠骨骼肌PPAR-α及脂代谢的影响
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摘要
目的：建立高脂饮食诱导ApoE敲基因小鼠胰岛素抵抗模型；观察运动对血脂、血糖、骨骼肌过氧化物酶体增殖物激活受体-α(peroxisome proliferator-activated receptor, PPAR-α)、脂酰辅酶A氧化酶(acyl-CoA oxidasel, Acyl)、烯酰辅酶A水解酶/L-3羟-CoA脱氢酶(enoyl-CoA-hydratase and 3-hydroxyacyl-CoA dehydrogenase, Enoy)mRNA表达的影响,探讨运动改善小鼠胰岛素抵抗的可能机制。
方法：将20只雄性ApoE基因敲除小鼠随机分为：高脂静止组(n=10)和高脂运动组(n=10)。高脂运动组,予以高脂饮食并运动训练12周。高脂静止组除不进行运动干预外,余处理同高脂运动组。另外C57BL/6J小鼠(n=8)作为正常对照组,常规饮食喂养12周。干预12周后,腹腔麻醉,摘眼球取静脉血。测定总胆固醇(TC)、甘油三脂(TG)、游离脂肪酸(FFA)、高密度脂蛋白胆固醇(HDL)、低密度脂蛋白胆固醇(LDL),空腹胰岛素(FIN),空腹葡萄糖(FPG)水平,并计算胰岛素抵抗指数(Homa-IRI),以确定胰岛素抵抗模型成功的建立。迅速取下双侧腓肠肌,一侧备电镜下观察分析超微结构,另一侧备测PCR。采用RT-PCR方法检测骨骼肌组织中过氧化物酶体增殖物激活受体-α(PPAR-α)、脂酰辅酶A氧化酶(Acyl)、烯酰辅酶A水解酶/L-3羟-CoA脱氢酶双(Enoy)mRNA。
结果：①与正常对照组相比较,高脂静止组FIN、FPG和Homa-IRI水平明显升高(P<0.01)；与高脂静止组相比较,高脂运动组FIN、FPG和Homa-IRI明显降低(P分别<0.05、0.01、0.01)。②与正常对照组相比较,高脂静止组TC、LDL、FFA水平明显升高(P<0.01)。与高脂静止组相比较,高脂运动组TC、LDL、FFA水平明显降低(P分别<0.05、0.05、0.01),HDL水平明显升高(P<0.05)。③高脂静止组：线粒体水肿,肌膜下水肿、内肌原纤维间水肿,见肌溶解灶。高脂运动组：肌细胞形态结构基本正常。肌原纤维间轻度水肿。肌纤维排列整齐,未见肌溶解、肌膜下水肿等病理征象。④干预12周后,高脂静止组与正常对照组相比较,PPAR-α、Acyl和Enoy mRNA表达明显减少(P<0.01)；高脂运动组与高脂静止组相比较,PPAR-α、Acyl和Enoy mRNA表达明显增加(P<0.01)。
结论：1、运动可以明显改善ApoE基因敲除小鼠胰岛素抵抗。2、运动上调骨骼肌组织PPAR-α表达、进而上调Acyl与Enoy的表达,使脂肪酸氧化作用增强,改善脂代谢,从而减轻胰岛素抵抗,可能是运动改善ApoE基因敲除小鼠胰岛素抵抗的机制之一
OBJECTIVES:To establish a model of ApoE knockout mice with insulin resistance induced by high fat diet, and explore the possible mechanisms that swimming training could improve insulin resistance by examining on the concentrations of serum free fatty acid(FFA) and glucose, and the mRNA expression of peroxisome proliferator-activated receptor(PPAR-α), acyl-CoA oxidase1 (ACYL), enoy-CoA-hydratase and 3-hydroxyacyl-CoA dehydrogenase (ENOY) in the skeletal muscle,
METHODS:Twenty male ApoE knockout mice were randomly divided into two groups:the high-fat diet group (HFD, n=10)and the high-fat diet group with exercise training (HFD+Ex, n=10). The HFD group were fed with high-fat diet, which was identical to the HFD+Ex group except 12 weeks'swimming training. And as the control group, ten healthy male C57BL/6j(ND,n=8) mice were fed with normal diet for 12 weeks. After 12 weeks intervention, the mice were sacrificed. Serum insulin and glucose were determined, and Homa-IRI was calculated to certain the establishment of insulin resistance. Serum total cholesterol (TC), trigiyceride (TG), high-density lipoprotein cholesterol (HDL),low-density liporeotein cholesterol (LDL) and free fatty acid (FFA) were determined. The bilateral gastrocnemiuses were cut for analyzing ultrastructure of sketletal muscle by the transmission electron microscope and measuring the mRNA expression of PPAR-a, ACYL and ENOY in skeletal muscle by reverse transcription polymerase chain reaction(RT-PCR).
RESULTS:①Compared with the ND group, fasting glucose, insulin and Homa-IRI of the HFD group were significantly higher (P<0.01). Compared with the HFD group, fasting insulin, glucose and HOMA-IR of the HFD+Ex group were significantly lower (P<0.05,0.01,0.01)。②Compared with the ND group,TC, LDL, FFA of HFD group were significantly higher (P<0.01). Compared with the HFD group, TC, LDL and FFA of the HFD+Ex group were significantly lower (P<0.05,0.05, 0.01), while HDL was significantly higher (p<0.05).③The transmission electron microscope showed that the myofibrils of ND group remained intergrity, the structure of sarcomere weas intact and clear.; HFD group appeared the sarcolemma edema, mitochondrial swelling, focal myocytolysis and edema within myofibrils, while HFD+Ex group reveresed pathological changes of the above.④Compared with the ND group, the mRNA expression of PPAR-a, ACYL and ENOY of the HFD group were significantly deceased(P<0.01); Compared with the HFD group, the mRNA expression of the above in the HFD+Ex group were significantly increased(P<0.01).
CONCLUSION:①Swimming training could improve insulin resistance of ApoE knockout mice.②Swimming training could improve insulin resistance possibly through upregulating the expression of PPAR-a, ACYL and ENOY mRNA.
方法：将20只雄性ApoE基因敲除小鼠随机分为：高脂静止组(n=10)和高脂运动组(n=10)。高脂运动组,予以高脂饮食并运动训练12周。高脂静止组除不进行运动干预外,余处理同高脂运动组。另外C57BL/6J小鼠(n=8)作为正常对照组,常规饮食喂养12周。干预12周后,腹腔麻醉,摘眼球取静脉血。测定总胆固醇(TC)、甘油三脂(TG)、游离脂肪酸(FFA)、高密度脂蛋白胆固醇(HDL)、低密度脂蛋白胆固醇(LDL),空腹胰岛素(FIN),空腹葡萄糖(FPG)水平,并计算胰岛素抵抗指数(Homa-IRI),以确定胰岛素抵抗模型成功的建立。迅速取下双侧腓肠肌,一侧备电镜下观察分析超微结构,另一侧备测PCR。采用RT-PCR方法检测骨骼肌组织中过氧化物酶体增殖物激活受体-α(PPAR-α)、脂酰辅酶A氧化酶(Acyl)、烯酰辅酶A水解酶/L-3羟-CoA脱氢酶双(Enoy)mRNA。
结果：①与正常对照组相比较,高脂静止组FIN、FPG和Homa-IRI水平明显升高(P<0.01)；与高脂静止组相比较,高脂运动组FIN、FPG和Homa-IRI明显降低(P分别<0.05、0.01、0.01)。②与正常对照组相比较,高脂静止组TC、LDL、FFA水平明显升高(P<0.01)。与高脂静止组相比较,高脂运动组TC、LDL、FFA水平明显降低(P分别<0.05、0.05、0.01),HDL水平明显升高(P<0.05)。③高脂静止组：线粒体水肿,肌膜下水肿、内肌原纤维间水肿,见肌溶解灶。高脂运动组：肌细胞形态结构基本正常。肌原纤维间轻度水肿。肌纤维排列整齐,未见肌溶解、肌膜下水肿等病理征象。④干预12周后,高脂静止组与正常对照组相比较,PPAR-α、Acyl和Enoy mRNA表达明显减少(P<0.01)；高脂运动组与高脂静止组相比较,PPAR-α、Acyl和Enoy mRNA表达明显增加(P<0.01)。
结论：1、运动可以明显改善ApoE基因敲除小鼠胰岛素抵抗。2、运动上调骨骼肌组织PPAR-α表达、进而上调Acyl与Enoy的表达,使脂肪酸氧化作用增强,改善脂代谢,从而减轻胰岛素抵抗,可能是运动改善ApoE基因敲除小鼠胰岛素抵抗的机制之一
OBJECTIVES:To establish a model of ApoE knockout mice with insulin resistance induced by high fat diet, and explore the possible mechanisms that swimming training could improve insulin resistance by examining on the concentrations of serum free fatty acid(FFA) and glucose, and the mRNA expression of peroxisome proliferator-activated receptor(PPAR-α), acyl-CoA oxidase1 (ACYL), enoy-CoA-hydratase and 3-hydroxyacyl-CoA dehydrogenase (ENOY) in the skeletal muscle,
METHODS:Twenty male ApoE knockout mice were randomly divided into two groups:the high-fat diet group (HFD, n=10)and the high-fat diet group with exercise training (HFD+Ex, n=10). The HFD group were fed with high-fat diet, which was identical to the HFD+Ex group except 12 weeks'swimming training. And as the control group, ten healthy male C57BL/6j(ND,n=8) mice were fed with normal diet for 12 weeks. After 12 weeks intervention, the mice were sacrificed. Serum insulin and glucose were determined, and Homa-IRI was calculated to certain the establishment of insulin resistance. Serum total cholesterol (TC), trigiyceride (TG), high-density lipoprotein cholesterol (HDL),low-density liporeotein cholesterol (LDL) and free fatty acid (FFA) were determined. The bilateral gastrocnemiuses were cut for analyzing ultrastructure of sketletal muscle by the transmission electron microscope and measuring the mRNA expression of PPAR-a, ACYL and ENOY in skeletal muscle by reverse transcription polymerase chain reaction(RT-PCR).
RESULTS:①Compared with the ND group, fasting glucose, insulin and Homa-IRI of the HFD group were significantly higher (P<0.01). Compared with the HFD group, fasting insulin, glucose and HOMA-IR of the HFD+Ex group were significantly lower (P<0.05,0.01,0.01)。②Compared with the ND group,TC, LDL, FFA of HFD group were significantly higher (P<0.01). Compared with the HFD group, TC, LDL and FFA of the HFD+Ex group were significantly lower (P<0.05,0.05, 0.01), while HDL was significantly higher (p<0.05).③The transmission electron microscope showed that the myofibrils of ND group remained intergrity, the structure of sarcomere weas intact and clear.; HFD group appeared the sarcolemma edema, mitochondrial swelling, focal myocytolysis and edema within myofibrils, while HFD+Ex group reveresed pathological changes of the above.④Compared with the ND group, the mRNA expression of PPAR-a, ACYL and ENOY of the HFD group were significantly deceased(P<0.01); Compared with the HFD group, the mRNA expression of the above in the HFD+Ex group were significantly increased(P<0.01).
CONCLUSION:①Swimming training could improve insulin resistance of ApoE knockout mice.②Swimming training could improve insulin resistance possibly through upregulating the expression of PPAR-a, ACYL and ENOY mRNA.
引文
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