摘要目的 观察血管紧张素Ⅱ(AngⅡ)及氧化应激水平在慢性间歇低氧(CIH)大鼠肺组织中的动态变化,探讨其在慢性间歇低氧相关性肺损伤机制中的可能作用机制.方法 将72只雄性wistar大鼠用随机数字表法分为正常对照组(UC组)、实验对照组(SC组)、5％间歇低氧组(CIH组),每组再分为1、2、3、4周4个亚组,每个亚组6只大鼠.UC组不予任何处理,CIH组循环暴露于氮气和压缩空气中,SC组循环给予压缩空气.观察各亚组大鼠肺组织HE病理变化,检测肺组织MDA含量、SOD活性、AngⅡ蛋白、AngⅡmRNA表达水平.结果 肺组织病理检查可见CIH组肺泡间隔增厚,部分肺泡萎缩不张,肺泡上皮可见炎性细胞浸润,且随时间延长病理损伤逐渐加重,NC组及SC组未见明显病理损害;与UC组及SC组比较,CIH组大鼠肺组织AngⅡ蛋白表达量及AngⅡmRNA水平于各个时间点均逐渐增加(21.3±1.7、26.5 ±1.3、34.6±2.2、36.3±0.9,均P＜0.05),MDA含量在1、2、3、4周逐渐增高[(2.3±0.7)、(2.9±0.4)、(3.7±0.7)、(5.2 ±0.1)nmol/mg],于4周达到高峰,而SOD活性于各个时间点均逐渐下降(均P＜0.05);并且CIH组肺组织AngⅡ蛋白、AngⅡmRNA水平与MDA含量均呈正相关(r=0.751,0.782,P＜0.01),而AngⅡ蛋白、AngⅡmRNA含量与SOD活性均呈负相关(r=-0.743,-0.904,P＜0.01).结论 慢性间歇低氧可激活氧化应激和AngⅡ,二者互为因果,可能是慢性间歇低氧肺损伤的重要发生机制.

abstractsObjective To observe the changes of angiotensin Ⅱ and the levels of oxidation stress during the development of chronic intermittent hypoxia (CIH)-induced pulmonary injury in rats,and the effect in the mechanism of CIH-induced pulmonary injury.Methods Seventy-two male Wistar rats were divided into three groups:control group (UC),sham control group (SC) and chronic intermittent hypoxia group (CIH).The three groups were also divided into 1 w,2 w,3 w,4 w time subgroups,and each time subgroup has 6 rats.UC rats were not treated,The CIH rats were subjected to alternating cycles of nitrogen and compressed air,while SC rats were similarly treated but received compressed air instead of nitrogen.After the experiment,sections of pulmonary were stained with hematoxylin-eosin (HE) and the level of SOD,MDA,Ang Ⅱ and Ang Ⅱ mRNA in rat homogenate pulmonary were measured.Results Pulmonary histology revealed that the CIH group showed high levels of interstitial edema,alveolar atelectasis,inflammatory cell infiltration of alveolar epithelial cell,pulmonary injury were serious in 1 w,2 w,3 w,4 w.But the pulmonary histology of the NC group and the SC group was normal.Compared with the UC group and SC group,the expression of angiotensin Ⅱ (Ang Ⅱ) protein,the levels of Ang Ⅱ mRNA in each time point in CIH group were increased gradually (P ＜ 0.05),the content of MDA were increased in 1 w,2 w,3 w,4 w (P ＜ 0.05),they had reached the peak all at 4 w;while the SOD in each time point in CIH group were decreased gradually (P ＜ 0.05) compared with that in UC group and SC group;the Ang Ⅱ and Ang Ⅱ mRNA levels of CIH in pulmonary showed positive correlation with MDA(r =0.751,0.782,P ＜0.01);while the Ang Ⅱ and Ang Ⅱ mRNA levels of CIH in pulmonary showed negative correlation with SOD [r =-0.743,-0.904,P ＜ 0.01].Conclusion CIH can activate oxidation stress and Ang Ⅱ,which were mutually causal and maybe an important mechanism of CIH-induced pulmonary injury.