Effects Of Aerobic Exercise On Kidney Injury And Endoplasmic Reticulum Stress In CIH Mice

Obstructive sleep apnea-hypopnea syndrome(OSAHS)is a type of sleep apnea(SDB)mainly characterized by repeated obstruction of the upper airway during sleep,and followed by hypoventilation and apnea,and the body’s repeated suffering from intermittent hypoxia(CIH)/reoxygenation is a clinical syndrome accompanied by snoring and frequent declines in blood oxygen saturation.According to previous studies,exercise has a significant protective effect on multiple organ damage in OSAHS patients,but the specific mechanism has not yet been determined.Object:To investigate the effects of aerobic exercise on kidney injury and endoplasmic reticulum stress(ERS)in CIH mice.Methods:Six-week-old male C57BL/6 mice were selected.weighing 20-25 g,for a total of 40 mice.The mice were randomly divided into 4 groups:control group(C),exercise control group(E),intermittent hypoxia group(H),and intermittent hypoxia+exercise group(HE),10 mice in each group.A self-designed computer-controlled chronic intermittent hypoxia device was used for CIH modeling.Group C was raised normally for 5 weeks.In group E mice,the treadmill exercise was performed in normoxia condition for one week,and the treadmill exercise was performed for 1 hour every day from the 2nd week.The adaptive and formal exercise were performed for 5 weeks.Group H was treated with intermittent hypoxia for 8 h/d,5 weeks.In the first week of the HE group,adaptive treadmill exercise was performed after CIH treatment.Starting from the second week,after 8 hours of CIH treantment every day,the treadmill exercise was performed for 1 hour,and all the exercises lasted for 5 weeks.After sampling,the degree of renal fibrosis was observed by Masson staining.The mRNA expression levels of transforming growth factor(TGFβ-1),collagen 1(Collagen 1)and.apoptosis-related gene C/EBP Homologous Protein(CHOP)were detected by RT-PCR.Western Blotting is used to detect the phosphorylation level of the ERS regulatory protein eukaryotic initiation factor 2 subunit a(eIF2α)and the expression of activating transcription factor 4(ATF4)Results:(1)Masson staining results of mice in each group showed that CIH caused edema andstructural abnormalitie s in the kidney tissue of m ice,large-scale necrosis or swelling of glomeruli,and widening or narrowing of the cystic cavity.There are a large number of collagen fibers around the renal interstitial and blood vessels,and the degree of fibrosis is severe.Aerobic exercise significantly improved the renal pathological changes in group HE mice.Compared with group C,the mRNA expression of renal fibrosis related factor TGF-β1 in group H was significantly increased(P<0.01).Aerobic exercise can significantly reduce TGF-β1 mRNA expression of group HE mice,which is significantly lower than that of group H mice(P<0.05).At the same time,the mRNA expression level of Collagen 1 was significantly higher than that of group C(P<0.01),and the mRNA expression level of Collagen 1 of group HE was significantly lower than that of group H(P<0.05).(2)Compared with group C,the expression of endoplasmic reticulum stress-related gene CHOP in group H was significantly increased(P<0.01).Compared with group H,aerobic exercise significantly reduced the expression of CHOP in group HE(P<0.05).(3)It was showed by Western Blotting results that compared with group C,the phosphorylation level of ERS regulator eIF2α(p-eIF2α)of group H was significantly increased(P<0.01).There was a significant decrease in the expression of p-eIF2a of HE group compared with that of group H,(P<0.05).At the same time,the protein expression of ERS regulator ATF4 in group H was significantly higher than that in group C(P<0.01),and the protein expression of ATF4 in group HE was significantly lower than that in group H(P<0.01).Conclusion:(1)Aerobic exercise has a protective effect on renal fibrosis of mice induced by chronic intermittent hypoxia.(2)Aerobic exercise reduces the level of endoplasmic reticulum stress in kidney tissues by down-regulating the protein expression of p-eIF2α and ATF4,thereby reducing the degree of renal fibrosis and apoptosis,which protecting the kidney function of CIH mice.