Role of Endoplasmic Reticulum Stress in Exercise Training and Resveratrol-induced Prevention of NAFLD Rat Liver Cell Apoptosis

Objective:To observe the impact on exercise and resveratrol(RSV)for blood lipids,liver cells apoptosis and endoplasmic reticulum stress on nonalcoholic fatty liver rats.Methods:70 SPF male SD rats were divided into seven groups,the normal control group(NC),high fat group(HF),model with low intensity-endurance exercise group(LE),model with middle intensity-endurance exercise group(ME),model with increment intensity-endurance exercise group(IE),RSV group,RSV with middle intensity exercise group(RE),10 rats in each group.rats were arranged to run on the treadmill 60 min per day and 5 days per week.Rats were given by gavage of resveratrol at the dose of 40mg/day,and 7 days a week.All the intervention lasted for 6 weeks.Blood lipids were determined,morphology of liver tissue was observed by making HE sections of liver tissue,the expression of Bax and Bcl-2were detected by immunohistochemical method,and cells apoptosis was determined by TUNEL,the protein expression of GRP78,Caspase3,IRE1,p-IRE1,JNK1,PERK,eIF2αand CHOP were detected by Western-blot.Results:Compared to HF group,the content of TG,TC,FFA,LDL-c on NAFLD rats' serum decreased.The expression of Bax decreased and cell apoptosis reduced.The expression of Bcl-2 and HDL-c increased.Compared to HF group,the protein expression of IRE1,PERK and the ratio of GRP78/Caspase3 increased.The protein expression of Caspase3,p-IRE1,eIF2α,JNK1 and CHOP decreased.The effect of ME group was better than LE group and IE group and RE group was the best in all groups.Conclusions:1)Duplicating the model of NAFLD after 16 weeks high-fat feeding,the enablement of mitochondrial apoptotic pathway of liver cells was related to the ERS induce the pathway of IRE1/JNK1 and the pathway eIF2α/CHOP on NAFLD rats.2)The different intensity of endurance exercise was improved blood lipids and liver cells apoptosis on NAFLD rats in different levels,but ME group was better than other exercise groups,this may depends on the regulation of liver cells mediated endoplasmic reticulum stress signaling pathways IRE1/JNK1 and eIF2α/CHOP.3)Resveratrol could improve apoptosis of liver cells on NAFLD rats,but not depends on regulation of ERS signaling pathway.4)RE group reminds that resveratrol can strengthen the control of endurance exercise to ERS signal pathway IRE1/JNK and elf-2α/CHOP,to improved lipid metabolism and apoptosis in liver cells of NAFLD rats more effective.