Relationship Between OSAHS And NAFLD In Elderly Adults And Preliminary Study On Its Underlying Mechanism

Purpose Obstructive sleep apnea(OSAHS)is closely related to non-alcoholic fatty liver disease(NAFLD),but there is no study on the relationship between OSAHS and non-alcoholic fatty liver disease(NAFLD)in the elderly.Meanwhile,the mechanism of liver injury caused by chronic intermittent hypoxia characterized by OSAHS is still unclear,and endoplasmic reticulum stress may play a role in it.The purpose of this study is to explore the relationship between OSAHS and NAFLD in the elderly,and to explore the role of endoplasmic reticulum stress in intermittent hypoxia-induced liver injury and its possible mechanism through cell experiments.Methods In the clinical study,according to inclusion and exclusion criteria,we recruited patients over 65 years of age suspected of having sleep apnea disorders and receiving polysomnography between January 2017 and December 2018.Patients were grouped according to apnea-hypopnea index(AHI)and analyzed for different severity courses in elderly patients with NAFLD.The differences between the patients with OSAHS were analyzed by grouping the patients according to whether NAFLD existed,and the possible risk factors of NAFLD were evaluated by logistic regression analysis.In basic research,L02 cells(normal human hepatocytes)were cultured for 4,8,and 12 hours under normal or intermittent hypoxia conditions.Some L02 cells treated with intermittent hypoxia were treated with 4-PBA one hour before exposure to hypoxia to observe the effects of 4-PBA on liver injury induced by intermittent hypoxia,hepatocyte apoptosis,endoplasmic reticulum stress and PERK-eIFa2-ATF4-CHOP apoptosis pathway.Results Clinical study showed that there was no significant difference in liver enzymes(ALT,AST,GGT)among the groups according to the severity of OSAHS(AHI)in the elderly NAFLD patients;however,there were significant differences in TG,ALT,AST,GGT,TS90%,ODI and AHI between the groups according to the presence of NAFLD in the elderly OSAHS patients;and BMI,TS90% and ODI might be the risk factors for NAFLD in elderly OSAHS patients.Basic research showed that 1.intermittent hypoxia can induce hepatocyte apoptosis;2.intermittent hypoxia can induce endoplasmic reticulum stress(ERS);3.intermittent hypoxia can cause liverinjury;4.4-PBA can alleviate intermittent hypoxia induced hepatocyte injury;5.4-PBA can alleviate intermittent hypoxia induced hepatocyte injury by inhibiting cell apoptosis;6.4-PBA inhibited the ERS related apoptosis pathway(PERK-eIF2a-ATF4-CHOP),but did not inhibit the unfolded protein response(UPR)induced by intermittent hypoxia.Conclusions 1.The characteristic chronic intermittent hypoxia of OSAHS may not result in significant elevation of liver enzymes in elderly OSAHS patients.2.BMI,TS90% and ODI may be risk factors for the occurrence and development of NAFLD in elderly OSAHS patients.Therefore,controlling body weight and improving sleep hypoxemia may reduce or prevent the occurrence of NAFLD in elderly OSAHS patients.In addition,BMI,TS90% and ODI may also be used as predictors of NAFLD in elderly OSAHS patients;3.4-PBA attenuates intermittent hypoxia induced hepatocyte injury by inhibiting ERS mediated cell apoptosis,rather than by reducing UPR.