Effect Of Chronic Intermittent Hypoxia On Inflammation And Vascular Endothelial Injury In Rats

Back ground:Obstructive sleep apnea-hypopnea syndrome(OSAHS)is the most representative disease of sleep disorder,characterized by repeated apnea and hypopnea during sleep.OSAHS has been considered as an independent risk factor for hypertension,coronary heart disease,stroke and so on.Chronic intermittent hypoxia(CIH)is one of the most important mechanism of tissue injure in OSAHS patients.The oxidative stress,inflammatory processes and high sympathetic activity(SNA)induced by CIH are important to endothelial dysfunction[2,3,4],whose pathogenic mechanism are incompletely understood.Objectives:We designed a rat model of CIH in order to explore the relationship of CIH,endothelial dysfunction and the expression of TNF-?,IL-10,YKL-40,NF-?B.It's our goal to understand the mechanisms and provide effective theoretical basis for prevention and treatment of OSAHS and its complication.Methods:The first part:Established and validated a rat model of CIH.Twenty male Wistar rats were randomly divided into the two groups:CIH group and the normoxia group.Eight weeks later,We sacrificed all rats to collect serum and Aorta.The second part:We detected the concentration of serum TNF-??IL-10?YKL-40 by ELISA assay.We observed the feature of the general pathological changes(HE staining)and the expression of YKL-40,NF-?Bp65 protein in Endothelium of aorta(immunohistochemistry staining).Results:The first part:Blood gas analysis show that the PO2 and SaO2 in CIH group were felled first and then increased,which were similar with the change of oxygen concentration in the chamber.The second part:1.ELISA assay of serum: serum level of IL-10 was significantly decreased in CIH group(P<0.05);There were no specific differences of the concentration of YKL-40 in serum between CIH group and normoxia control group(P>0.05);there were no expression of TNF-? in serum in both group.2.HE staining of aorta: In the normoxic group,the aortic vascular endothelium was smooth without exfoliation.In the CIH group,the aortic vascular endothelium was not smooth,and endothelial cells were locally absent.3.Immunohistochemistry staining of aorta: The expression of NF-?B in aorta in CIH group was obviously increased compared with which in the normoxia control group(P<0.05);There were no specific differences of the expression of YKL-40 in aorta between CIH group and normoxia control group(P>0.05).Conclusions:1.The rat model of chronic intermittent hypoxia can imitate the pattern of intermittent hypoxia of OSAHS.2.Chronic intermittent hypoxia induced vascular endothelial injury,whose mechanism was likely to do with the decrease of serum level of IL-10 and the increasing expression of NF-?B in aorta.