Mechanism Of Chronic Intermittent Hypoxia Induced Renal Injury In Rats By Endoplasmic Reticulum Stress And Renal Function Recovery After Reoxygenation

Objective To observe the mechanism of obstructive sleep apnea hypopnea syndrome(OSAHS)on renal injury induced by common diet and high fat diet,and to kown the recovery of renal tissue after reoxygenation.This study was based on chronic intermittent hypoxia(CIH),high-fat diet simulating OSHAS and high-fat diet,which induceds rat kidney damage by activating endoplasmic reticulum stress response(ERS).Reoxygenation simulating cntinuous positive airway pressure(CPAP)treatment,observation of renal tissue structure and function recovery.To provide a new diagnose and treatment for the clinical treatment.Methods 48 healthy male Wistar rats of SPF grade were randomly divided into 4 groups(n=12).group A: control group(normoxia and common diet group),group B: high fat group(normoxia and high fat diet),Group C: CIH group(CIH and common diet group),group D: CIH and high fat diet group(CIH and high fat diet group).Detection of serum CystatinC(Cys-C),high density lipoprotein(HDL).And detected the renal CHOP protein was detected by immunohistochemistry.The changes of renal pathological structure were observed by HE staining.And the ultrastructural changes of glomeruli and renal tubules were observed under electron microscope.And then in the reoxygenation and the group of the original diet under the conditions of 2 weeks to repeat the above tests,and compare.Results The levels of Cys-C in group B,group C and group D were significantly higher than those in group A(P <0.05).The levels of HDL in group B and group D were significantly lower than those in group A(P <0.05),but there was no significant difference between group C and group A(P> 0.05).The mean density of ERS marker protein CHOP in group B,group C and group D was significantly higher than that in group A(P <0.05).HE staining showed that there was no obvious abnormality in the renal tissue of group A,proximal tubule epithelial cells in the B group and C group of small edema,D group was mostly edematous;Electron microscopic observation,B group,C group the partly renal tubular epithelial cell focal nuclear pyknosis,brush edge sparse and fall off,D group has a large tubular epithelial cell nuclear pyknosis,brush edgeSparse and off.There was no significant change in Cys-C level after reoxygenation in group A and group B,and significantly increased in group C(P <0.05),In group D,there was no significant difference(P> 0.05).The mean density of CHOP protein in the kidney after reoxygenation.There was no significant difference between group A and group B(P> 0.05),the levels of group C and D were significantly lower than those before reoxygenation(P <0.05).Under light microscope and electron microscope,there was no obvious abnormality in group A,and the edema was slightly increased in group B compared with before reoxygenation.Compared with group C and group D,renal tissue was improved after reoxygenation.Conclusion 1.Establishment of CIH combined with high fat diet.2.CIH can activate the ERS mediated renal tubular epithelial apoptosis,so that the ultrastructure of the kidney changes,and then kidney damage.3.Reoxygenation can reduce the ERS response,so that renal structure and renal function improved.