Pulmonary Injury In Rats Exposed To Chronic Intermittent Hypoxia And The Effect Of Eodaravone

Objectives To establish a chronic imtermittent hypoxia(CIH) animal model in rats, to observe the hematoxylin-eosin and the level of SOD?MDA and Ang??ACE2?Apelin?Ang?m RNA in rat homogenate pulmonary were measured, investigate the mechanism of pulmonary injury in rats exposed to chronic intermittent hypoxia and to investigate the effect of Edaravone.Methods Ninety- six male Wistar rats were divided into four groups: uncontrol group(NC), chronic intermittent hypoxia group(CIH), chronic intermittent hypoxia normal saline matched group(NS), chronic intermittent hypoxia edaravone intervention group(NE), each group were only 24. After the experiment,sections of pulmonary were stained with hematoxylin-eosin and the level of SOD ? MDA ? PO2 in rat homogenate pulmonary were measured. The changes of ACE2?Apelin?Ang?and Ang?m RNA in pulmonary were observed by immunohistochemical and PCR.Results 1 Groups of rats blood gas analysis results: CIH group, the NE, NS group rats blood oxygen partial pressure lowest 37.6 mm Hg and 35.8 mm Hg and 35.8 mm Hg, NC group blood oxygen partial pressure maintenance in98-100 mm Hg.2 Compared with the NC, the content of MDA were increased in 1w, 2w, 3w, 4w, they had reached the peak all at 4w; while the SOD in CIH ?NE and NS group were decreased gradually. Compared with NC group,MDA in pulmonary increased markedly in CIH?NE and NS groups, SOD in pulmonary decreased markedly in CIH ? NE and NS groups(P <0.05);compare with NS and CIH group, MDA in pulmonary decreased significantly in NE group,SOD in pulmonary decreased markedly in NE group(P <0.05). 3 Pulmonary histology revealed that the CIH?NE and NC group showed high levels of interstitial edema,alveolar atelectasis,inflammatory cell infiltration of alveolarepithelial cell,pulmonary injury were serious in 1w, 2w,3w,4w.But the pulmonary histology of the NC was normal. Compared with the NS group, pulmonary injury of NE group 1w, 2w,3w,4w, significantly decreased. 4 Compared with the NC,CIH ?NS?NE Ang II protein expression in 1w, 2w, 3w, 4w IOD values were significantly higher;compared with NC, Ang II protein in pulmonary increased markedly in CIH ?NS and NE;compare with NS and CIH,Ang II protein expression in pulmonary decreased significantly in NE(P <0.05). 5 Compared with the NC, the expression of ACE2 protein in CIH and NS were increased gradually,they reached their peak at 2w and then decreased; while the expression of ACE2 protein in NE group were decreased gradually,they reached their peak at 2W and then increased. Compared with NC,ACE2 protein in pulmonary increased markedly in CIH and NS(P <0.05);compare with NS and CIH, NE in the 1w, 2w,4w ACE2 protein expression in pulmonary increased markedly in(P <0.05),while there was no significant difference in 3w(P >0.05).6 The expression of Apelin protein in CIH and NS were decreased gradually,they reached their peak at 2W and then increased; while the expression of Apelin protein in NE group were decreased gradually.Compared with NC, CIH and NS in the 1w, 2w Apelin protein expression in pulmonary decreased markedly(P <0.05),while there was no significant difference in 3w(P >0.05)and increased markedly in 4w(P <0.05), NE in the 3w, 4w Apelin protein expression in pulmonary decreased markedly. Compared with CIH and NS, NE in the1 w,2w,3w,4w Apelin protein expressionin pulmonary decreased markedly(P <0.05).7 Compared with the NC group,CIH ?NS and NE group Ang II m RNA levels in 1w, 2w, 3w, 4w were significantly higher;compared with NC group, Ang IIm RNA in pulmonary increased markedly in CIH ? NS and NE;compare with NS and CIH Ang IIm RNA in pulmonary,decreased significantly in NE(P <0.05). 8 Ang IIm RNA and MDA exists a positive correlation(r=0.782 P <0.01 was statistically significant) in CIH; Ang IIm RNA and SOD exists a negative, correlation((r=-0.804, P<0.01 statistically significant) in CIH. Ang IIm RNA and MDA exists a positive correlation(r=0.876,P <0.01 was statistically significant) in NE; Ang IIm RNA and SOD exists a negative correlation((r=-0.866,P <0.01 statistically significant) in NE.Conclusions Intermittent hypoxia-induced rat pulmonary injury.Intermittent hypoxia rat pulmonary injury was interrelated with OS and RAS imbalance in rats.Edaravone can prevents CIH-indueed disease of respiratory system by alleviating OS and maintaining RAS balance.