河北医科大学学报

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游泳训练对小鼠胰岛素抵抗及肝脏PPAR-γ信号通路的影响

  

  1. 1.河北省胸科医院内分泌科,河北 石家庄 050041;2.河北省胸科医院呼吸科,河北 石家庄 050041;
    3.中南大学湘雅医院康复科,湖南 长沙 410008
  • 出版日期:2019-10-25 发布日期:2019-10-21
  • 作者简介:冯彦景(1981-),女,河北石家庄人,河北省胸科医院主治医师,医学硕士,从事内分泌疾病诊治研究。

Effects of swimming training on insulin resistance and liver PPAR-gamma signaling pathway in mice #br#

  1. 1.Department of Endocrine, Hebei Chest Hospital, Shijiazhuang 050041, China; 2.Department of
    Respiratory, Hebei Chest Hospital, Shijiazhuang 050041, China; 3.Department of Rehabilitation,
    Xiangya Hospital of Central South University, Hunan Province, Changsha 410008, China
  • Online:2019-10-25 Published:2019-10-21

摘要: [摘要]
〖HTH〗目的〖HTSS〗观察游泳训练对小鼠肝脏脂含量及对过氧化物酶体增殖物激活受体γ(peroxisome proliferator activated receptor-γ,PPAR-γ)信号通路的影响,探讨运动改善胰岛素抵抗的作用机制。
〖HTH〗方法〖HTSS〗将31只8周龄健康雄性C57BL/6J小鼠随机分为正常组(n=10)、高脂组(n=10)和运动组(n=11)。采用高脂饮食建立胰岛素抵抗动物模型,运动组给予12周游泳训练。干预前后记录小鼠体重,检测空腹血糖(fasting  blood glucose,FBG)和空腹血胰岛素(fasting insulin,FINS),HOMA法计算胰岛素抵抗指数(insulin resistance index,IRI),逆转录聚合酶链反应法检测肝组织PPAR-γ、丙酮酸脱氢酶激酶4(pymvate dehydrogena kinase 4,PDK4)及丙酮酸脱氢酶(pyruvate dehydrogenase,PDH)mRNA表达水平,光镜和电镜观察各组肝脏脂肪含量变化。
〖HTH〗结果〖HTSS〗干预12周后,3组体重均大于干预前,高脂组体重显著大于正常组和运动组(P<0.05)。高脂组和运动组FINS、FBG、IRI明显高于正常组,运动组FINS、FBG、IRI明显低于高脂组(P<0.05)。HE染色显示:高脂组小鼠肝细胞肝细胞呈弥漫性脂肪变性,胞质内充满大量大小不等的圆形脂滴,脂滴绕于胞核周围或胞质一侧,将核挤向一边,有的呈印戒形;运动组小鼠肝细胞胞质内偶见脂滴形成。电镜观察显示:高脂组肝细胞内可见大量脂滴沉积;运动组肝细胞内有脂褐素样物质残留,偶见脂滴沉积。高脂组PPAR-γ mRNA表达低于正常组,运动组PPAR-γ mRNA表达高于正常组,高脂组和运动组PDK4 mRNA表达高于正常组,PDH mRNA表达低于正常组;运动组PPAR-γ mRNA和PDH mRNA表达明显高于高脂组,PDK4 mRNA表达增加低于高脂组(P<0.05)。
〖HTH〗结论〖HTSS〗运动可以改善胰岛素抵抗,可能与减少小鼠肝脏脂肪变性、上调小鼠肝组织PPAR-γ mRNA表达、减少PDK4 mRNA表达、增加PDH mRNA表达有关。

关键词: 胰岛素抵抗, 过氧化物酶体增殖物激活受体&gamma, 游泳

Abstract: [Abstract]Objective〖HTSS〗To observe the effect of swimming training on liver fat content and peroxisome proliferator activated receptor-γ(PPAR-γ) signaling pathway in mice and discuss the mechanism of exercise improving insulin resistance.
〖HTH〗〖WTHZ〗Methods〖HTSS〗Thirty-one healthy 8-week-old male C57BL/6J mice were randomly divided into normal group(n=10), high-fat group(n=10) and exercise group(n=11). Insulin resistance animal model was established by high fat diet. The exercise group was given 12 weeks swimming training. The weight of mice was recorded before and after intervention. Fasting blood glucose(FBG) and fasting insulin(FINS) were measured. Insulin resistance index(IRI) was calculated by HOMA. PPAR-γ and pyruvate dehydrogenase kinase 4(PDK4) in liver tissue were detected by reverse transcription polymerase chain reaction(RT-PCR). The expression levels of kinase 4, PDK4 and pyruvate dehydrogenase(PDH) were observed by light and electron microscopy.
〖HTH〗〖WTHZ〗Results〖HTSS〗After 12 weeks of intervention, the weight of the three groups was significantly higher than that before intervention, and the weight of the high-fat group was significantly higher than that of the normal group and the exercise group(P<0.05). FINS, FBG and IRI in the high-fat group and the sports group were significantly higher than those in the normal group, while FINS, FBG and IRI in the sports group were significantly lower than those in the high-fat group(P<0.05). HE staining showed that hepatocytes in the high-fat group presented diffuse steatosis, and the cytoplasm was filled with a large number of round lipid droplets of different sizes. Lipid droplets wrap around the nucleus or cytoplasmic side, squeezing the nucleus to one side, some in signed-ring shape. Lipid droplet formation was observed occasionally in the cytoplasm of hepatocytes of mice in the exercise group. Electron microscopy showed that a large number of lipid droplets were deposited in the hepatocytes of the high-lipid group. There were residual lipofuscin-like substances in liver cells of exercise group. The expression of PPAR-γ mRNA in the high-fat group was lower than that in the normal group, the expression of PPAR-γ mRNA in the exercise group was higher than that in the normal group, the expression of PDK4 mRNA in the high-fat group and exercise group was higher than that in the normal group, and the expression of PDH mRNA was lower than that in the normal group. The expression of PPAR-γ mRNA and PDH mRNA in the exercise group was significantly higher than that in the high-fat group, and the expression increase of PDK4 mRNA was lower than that in the high-fat group(P<0.05).
〖HTH〗〖WTHZ〗Conclusion〖HTSS〗Exercise can improve insulin resistance, which may be related to reducing liver steatosis in mice, up-regulating the expression of PPAR-γ mRNA in mouse liver tissue, reducing the expression of PDK4 mRNA, and increasing the expression of PDH mRNA.

Key words: insulin resistance; peroxisome proliferator activated receptor-&gamma, ; swimming