| Objective By studying the effects of intermittent hypoxia(IH)on hepatic injury and expression of adipokine chemerin in rats,we aim to explore the internal relationship between nonalcoholic fatty liver disease(NAFLD)and the expression of adipokine chemerin,and further to investigate the intervention effect of reoxygenation,so we can provide new ideas for the research and prevention of OSAHS related metabolic complications in the future.Methods According to the random number table,48 healthy male Wistar rats were choosen and divided into four groups(n = 12): normoxic + normal diet(NC + ND)group,normoxic + high fat diet(NC + HFD)group,intermittent hypoxia + normal diet(IH + ND)group,intermittent hypoxia + high fat diet(IH + HFD)group.ND group was given basic diet,and HFD group was given high-fat diet.IH group was exposed to intermittent hypoxic environment of 8h/d,while NC group received intermittent compressed air.At the end of the 6 weeks of experiment,we killed the rats and measured the weight and liver weight,the liver index was calculated,we collected the arterial blood and liver tissue samples.The liver enzymes and blood lipid were measured by automatic biochemical analyzer.We used oxidase-peroxidase method to measure the level of fasting plasma glucose(FPG)in serum and radioimmunoassay to mesure fasting insulin(FINS).The insulin resistance index(ISI)and insulin resistance index(IRI)were used to evaluate insulin resistance.Light microscopy and transmission electron microscopy were used to observe the liver tissue morphology and ultrastructural changes.The expression of chemerin in serum and liver tissue was detected by ELISA(double antibody sandwich method).The remaining rats in the IH group were reoxygenated for 2 weeks.The rats in the normal diet group were fed with basal diet,while high fat diet group were fed with high fat diet,and all the rats were killed at the end of 8 weeks.The detection indexes and methods were the same as above.Results Firstly,compared with NC + ND group,serum ALT,AST,FPG,FINS,IRI,TC,TG and LDL-C were significantly increased in IH + ND group.Compared with NC + HFD group,The levels of AST,FINS and IRI in IH + HFD group were increased.Compared with IH + ND group,the serum AST,FPG and TC standard in IH + HFD group were higher and the LDL-C level was significantly increased.No significant differences were existed between the other indicators.Secondly,compared with NC + ND group,the liver histological features of NC + HFD group,IH + ND group and IH + HFD group all showed non-alcoholic fatty liver disease under optical microscopy and transmission electron microscopy: NC + HFD group showed simple fatty liver and IH + ND group steatohepatitis,while IH + HFD group showed fatty liver and even slight liver fibrosis,which were more serious than IH + ND group and NC + HFD group.Thirdly,The expression level of serum chemerin in IH + ND group was significantly higher than that in NC + ND group,and the level in IH + HFD group was significantly increased than that in NC + HFD group and IH + ND group.There were no significant differences between the other indicators.Fourthly,serum chemerin levels were positively correlated with ALT(r = 0.526),AST(r = 0.742),FPG(r = 0.751),FINS(r = 0.764),IRI(r = 0.765),TC(r=0.791),LDL-C(r = 0.818)and body weight(r = 0.685),while negatively correlated with ISI(r =-0.692).Fifthly,Whether the occurrence of OSAHS-related NAFLD as the dependent variable,liver weight,body weight,LBR,AST,ALT,FPG,FINS,IRI,ISI,TC,TG,LDL-C,serum chemerin and liver chemerin were used as the independent variables,our logistic stepwise regression analysis showed that serum chemerin was a risk factor for OSAHS-associated NAFLD(OR = 1.197,P <0.01).Sixthly,compared with pre-reoxygenation,the body weight of IH + ND group was increased and IRI level decreased,the level of serum FPG and serum chemerin decreased significantly after reoxygenation,and the histological features of liver were still still appear to be steatohepatitis under optical microscope and transmission electron microscope.The expression level of serum FPG was decreased and serum chemerin significantly decreased in IH + HFD group compared with pre-reoxygenation,under optical microscope and transmission electron microscope,liver histological features were still expressed as steatohepatitis and even slight liver fibrosis.Conclusions Firstly,intermittent hypoxia can lead to glucose and lipid metabolism and liver injury in rats,mainly for NAFLD,under the condition of intermittent hypoxia combined with high fat diet,this metabolic disorder and liver injury can be more serious,suggesting that intermittent hypoxia may be an independent risk factor for the occurrence and progression of NAFLD.Secondly,the serum chemerin levels was significantly higher in the OSAHS-related NAFLD rats exposed to intermittent hypoxia,while there was no significant change in liver chemerin levels.Logistic stepwise regression analysis showed that serum chemerin was a risk factor for NAFLD,suggesting that serum chemerin could be used as an early adipokines predictor of OSAHS-related NAFLD.Thirdly,two weeks of reoxygenation therapy can not cause pathological changes in rat liver and significant changes in serum transaminase levels,but can reduce the level of FPG and even reduce insulin resistance,and also make serum chemerin level significantly decreased,suggesting that short-term CPAP treatment could not effectively improve OSAHS related NAFLD,but may stabilize and delay its progression to a certain extent,serum chemerin may serve as a new noninvasive marker for future treatment of OSAHS-related NAFLD. |
