The Effects Of Insulin Resistance By Expression Levels Of FoxO1and IRS-2 In Chronic Intermittent Hypoxia Rat Hepatocytes

Objective:By observing changes of the rat heptocytes histomorphology, and protein expression of insulin receptor substrate-2(IRS-2) and forkhead box O1(Fox O1) in heptocytes to investigate whether there is a correlation between IRS-2、 Fox O1 and insulin resistance in the environment of chronic intermittent hypoxia.Methods:Select 24 healthy male 6 weeks old SD rats were randomly divided into 3 groups, namely, normal control group(NC group), chronic intermittent hypoxia 4 weeks group(CIH4 group), chronic intermittent hypoxia 8 weeks group(CIH8 group), with 8 rats in each group. CIH4、CIH8 group were placed in intermittent low oxygen cabin. About 8 hours per day, the minimum oxygen concentration was6%~8% in animal chamber. NC group were placed in normal air cabin and fed. In 4 weeks、8 weeks and8 weeks,after fasting for 12 hours to measure fasting blood glucose and fasting insulin of CIH4、CIH8and NC group, using steady state model of insulin resistance index(HOMA-IR) and insulin sensitive index(insulin sensitive index, ISI) to evaluate insulin resistance, observing changes of the liver of rats histomorphology by dyeing HE method,and the heptocytes of rats was determined by immunohistochemical method in the expression of IRS-2 and Fox O1。Average gray value was used to represent the protein expression, and wich is inversely proportional to average gray value. A statistical analysis was also given.Results:Compared with NC group, the experimental group rats elevated fasting blood glucose, fasting insulin, HOMA-IR, and reduced ISI, with more obvious in CIH8 group,the difference was statistically significant(P<0.05). Compared with the NC group,the expression of IRS-2 protein was decreased in CIH4 and CIH8 groups;the expression of Fox O1 protein was increased in CIH4 and CIH8 groups(P<0.05),and being distributed in the nucleus.At the same time, Pearson correlation analysis showed that the average gray value of HOMA-IR and IRS-2 protein was positively correlated(r=0.857, P<0.05)and was negatively correlated(r=-0.926, P<0.05)with Fox O1 protein;the average gray value of ISI and IRS-2 protein was negatively correlated(r=-0.926, P<0.05)and was positively correlated(r=0.848,P<0.05)with Fox O1 protein.Conclusions:1. In the environment of intermittent hypoxia,the rat can lead to heptocytes damage, with more exposing time the degree of heptocytes damage get more serious.2. In the environment of intermittent hypoxia, the rat can lead to insulin resistance, with more exposing time the degree of heptocytes damage get more serious.3. Chronic intermittent hypoxia rat hepatocytes IRS-2 protein expression decreased, Fox O1 protein expression increased, and correlated with the degree of insulin resistance, indicating that these two proteins may be involved in chronic intermittent hypoxia-induced insulin resistance.