Chronic Intermittent Hypoxia Mediates Renal Injury Through PI3K/Akt/mTOR Autophagy Signaling Pathway And The Intervention Effect Of Edaravone

Objective: Establishing an animal model of chronic intermittent hypoxia(CIH)simulate the pathophysiological process of patients with obstructive sleep apnea hypopnea syndrome,to observe the renal injury of chronic intermittent hypoxia animal model,to explore the relationship between PI3 K / Akt / mTOR autophagy signal pathway and CIH mediated renal injury,and to observe the effect of edaravone on CIH mediated renal injury and autophagy signal pathway,so as to provide a new treatment direction for clinical prevention and treatment of renal injury caused by OSAHS.Methods:Thirty 8-week-old healthy male Wistar rats were randomly divided into three groups.They were group A(normal control group),group B(intermittent hypoxia group)and group C(intermittent hypoxia group + edaravone group).The normal control group was placed in normoxic environment,and the other two groups were placed in the marked intermittent hypoxia chamber.During the non modeling period,the three groups were raised in the same environment.Intermittent hypoxia modeling time was 8 hours a day for 8 weeks.After modeling,the levels of serum creatinine and urea nitrogen were detected;the morphological changes of kidney were observed by hematoxylin eosin staining under light microscope.The relative expression levels of Beclin 1,PI3 K,Akt and mTOR mRNA in kidney tissue were detected by real-time PCR.The expressions of Beclin 1,PI3 K,Akt and mTOR protein in kidney tissue were detected by immunohistochemistry.Results:(1)Compared with group A,the levels of blood serum creatinine and urea nitrogen in group B were significantly increased(P< 0.05);after edaravone intervention,the levels of blood urea serum creatinine and urea nitrogen in group C were significantly decreased(P< 0.05).(2)Under the light microscope,the structure of kidney in group A was normal,the glomerulus was filled and the gap was uniform,and there was no obvious abnormality in the morphology of renal tubular epithelial tissue;in group B,the glomerulus epithelial cells were sparse,the renal tubular epithelial cells were swollen and denatured,and the structure was disordered;in group C,the morphology of glomerulus gradually returned to normal,and some renal tubular epithelial cells were mild The morphology and structure of renal tubular epithelial cells were obviously improved.(3)Compared with group A,the mRNA levels of Beclin 1 in group B were significantly increased(P< 0.05),after edaravone intervention,compared with group B,the mRNA levels of Beclin 1 in group C were significantly decreased(P< 0.05).Conversely,compared with group A,the mRNA levels of PI3 K,Akt and mTOR in group B were significantly decreased(P< 0.05),after edaravone intervention,compared with group B,the mRNA levels of PI3 K,Akt and mTOR in group C were significantly increased(P< 0.05).(4)Compared with group A,the expression levels of Beclin 1 in group B were increased(P< 0.05),after edaravone intervention,compared with group B,the expression levels of Beclin 1 in group C were decreased(P< 0.05).Conversely,compared with group A,the expression levels of PI3 K,Akt and mTOR in group B were decreased(P < 0.05),after edaravone intervention,compared with group B,the expression levels of PI3 K,Akt and mTOR in group C were increased(P < 0.05).Conclusion:1.Chronic intermittent hypoxia can mediate renal injury in rats.Under the light microscope,the glomerular epithelial cells were sparse,the renal tubular epithelial cells were swollen and denatured,and the structure was disordered;the serum creatinine and serum urea nitrogen were increased.After edaravone intervention,glomerular morphology gradually returned to normal,serum creatinine and urea nitrogen decreased to normal level.2.Chronic intermittent hypoxia can increase the expression of beclin-1 and decrease the expression of PI3 K,Akt and mTOR,which may mediate renal injury by activating autophagy and inhibiting PI3 K /Akt / mTOR signaling pathway.3.Edaravone may reduce the level of autophagy through PI3 K / Akt / mTOR signaling pathway,so as to repair the damage of renal ultrastructure and improve renal function.