慢性间歇低氧对小鼠糖代谢及肝脏JNK/Akt表达的影响

Effect of intermittent hypoxia on glucose metabolism and expression of JNK/Akt in liver of mice

目的:探讨间歇低氧对小鼠糖代谢的影响以及相关信号通路的变化。方法:将30只C57/BL6J小鼠随机分为间歇空气组(对照组)和间歇低氧组,每天给予8 h的间歇空气或间歇低氧处理。造模7周后检测小鼠空腹血糖及餐后血糖,采用酶联免疫吸附试验(ELISA)检测空腹胰岛素,并行经腹腔葡萄糖耐量试验评估糖耐量。采用蛋白质印迹(Western blotting)技术检测小鼠肝脏中c-Jun氨基末端激酶(JNK)以及胰岛素信号通路中关键激酶蛋白激酶B(Akt)磷酸化水平的变化。结果:间歇低氧组小鼠空腹血糖显著高于对照组(P<0.01),2组空腹血清胰岛素无显著差异(P=0.637)。葡萄糖耐量试验表现为间歇低氧组糖耐量受损。间歇低氧组肝脏中炎症激酶JNK的磷酸化水平显著高于对照组(45.24±8.95比8.98±1.71,P<0.01),而Akt磷酸化水平显著低于对照组(46.93±4.25比66.92±11.49,P<0.01)。结论:间歇低氧可导致小鼠糖代谢异常,胰岛素敏感性下降,肝脏中炎症信号通路被激活,JNK磷酸化水平显著升高,胰岛素信号转导受到抑制,通路中重要激酶Akt磷酸化水平显著降低,JNK的激活可能在间歇低氧所致的糖代谢异常中起重要作用。

Objective To study the effect of intermittent hypoxia on glucose metabolism and the changes of relatedsignal transduction pathway in mice. Methods Thirty male C57/BL6J mice were randomly divided into intermittent airventilation group （IA group, n=15） and intermittent hypoxia group （IH group, n=15） by exposed correspondingly to inter-mittent air ventilation or intermittent hypoxia for 8 h every day. After 7 weeks exposure, fasting blood glucose and post-prandial blood glucose were determined. Enzyme linked immunosorbent assay （ELISA） was used to test the fasting seruminsulin. Intraperitoneal glucose tolerance test （IPGTF） was performed to assess the glucose tolerance. The phosphorylationof c-Jun N-terminal kinase （JNK） and phosphorylation of insulin signaling pathway kinase protein kinase B （Akt） in liverwere determined by Western blotting. Results After 7 weeks exposure, the fasting glucose of IH group was significantlyhigher than that of IA group （P〈0.01） and there was no significant difference in fasting serum insulin between the twogroups （P=0.637）. The results of IPGTY showed impaired glucose tolerance in IFI group. The level of phosphorylated-JNKwas higher （45.24±8.95 vs 8.98±1.71, P〈0.01） and phosphorylated-Akt was lower （46.93±4.25 vs 66.92±11.49, P〈0.01） inliver tissue of IH group than in that of IA group. Condusions Intermittent hypoxia impaired the glucose metabolism andinsulin sensitivity in mice. The inflammatory signaling pathway in liver was activated. The phosphorylation of JNK increased and the phosphorylation of Akt decreased significantly. The activation of JNK might play an important role in theglucose metabolic impairment induced by intermittent hypoxia.