The Effects Of The Expression Level Of GSK-3 And MTOR1 In Rat Hepatocytes During Intermittent Hypoxia On Insulin Resistance

Objective:Through observing the morphologic alteration and testing the expression of glycogen synthase kinase-3(GSK-3) and the mammalian target of rapamycin1(m TOR1) in models of intermittent hypoxic rat heptocytes, to investigate the effects of intermittent hypoxia on the insulin signaling pathways, and reflecting and the possible mechanism of insulin resistance(IR).Methods:24 healthy male SD rats at 6-week age were randomly divided into 3 groups, namely,intermittent air group(NC group), intermittent hypoxia 4 weeks group(IH4 group) and intermittent hypoxia 8 weeks group(IH8 group), with 8 rats in each group. From 9 to17(About 8 hours per day), when IH4 and IH8 group were exposed to the intermittent hypoxia environment of intermittent hypoxia cabin, NC group were given intermittent compressed air. Respectively, IH4 group in fourth weeks, NC group and IH8 group in eighth weeks after fasting for 12 hours, testing each group rats fasting blood glucose(FBG)and fasting insulin(FINS), using insulin sensitive index(ISI) and steady state model of insulin resistance index(HOMA-IR) to evaluate insulin resistance(IR); To observe the morphological changes of the rat heptocytes in each group with hematoxylin eosin(HE)staining, and to evaluate the injury degree by intermittent hypoxia. Detecting the expression of hepatic GSK-3 and m TOR1 by immunohistochemical method, taking the average grey value as the amount of protein expression of GSK-3 and m TOR1, and a statistical analysis of date was also given.Results:Compared with control group, the experimental group SD rats elevated FBG, FINS,HOMA-IR, and reduced ISI, which were more obvious in IH8 group, the difference was statistically significant(F values were 100.375, 69.90, 85.49, 62.52, all P<0.01); Compared with control group, the expression of GSK-3 and m TOR1 protein were increased in IH4 and IH8 group, especially in IH8 group, the difference was statistically significant(F values were 72.25, 148.01, all P<0.01). At the same time, Pearson correlation analysis showed that the average gray values of GSK-3 and m TOR1 were positively correlated to ISI(r=0.786, 0.811, all P<0.01), and negatively correlated with HOMA-IR(r=-0.882,-0.889, all P<0.01). HE staining showed that the structure of the rat heptocytes of NC group is complete, the nucleus is large and round; Bureau of the rat liver cell with intermittent hypoxia is necrosis, cell is swelling, cell membrane is destruct, cytoplasm is sparse,nucleus staining is deepen and inflammatory cells are infiltrating and the damage of liver cell structure is more obvious with the prolonged intermittent hypoxia.Conclusions:1. Intermittent hypoxia can damage the heptocytes in rats and make the insulin resistance happen, and with more intermittent hypoxia exposure time, the heptocytes destruction and insulin resistance worse.2. During intermittent hypoxia, the GSK-3 and m TOR1 protein expression in rat heptocytes were upregulated, and the expression was positively correlated with the intermittent hypoxia time.3. During intermittent hypoxia, the GSK-3 and m TOR1 protein expression rat heptocytes were significantly correlated with ISI and HOMA-IR, suggesting that these two proteins may play important roles in the occurrence and development of insulin resistance caused by intermittent hypoxia.