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目的观察血管紧张素转换酶2(ACE2)在慢性间歇低氧(CIH)大鼠肺组织氧化应激损伤中的动态变化,探讨其在CIH肺损伤中可能的作用机制。方法 96只Wistar大鼠随机分为正常对照组(UC组)、CIH组、依达拉奉治疗组(NE组)、安慰剂(0.9%NaCl)治疗组(NS组),并分为1周、2周、3周、4周4个时间亚组,每亚组6只大鼠。UC组暴露于空气中,CIH组、NE组及NS组分别暴露于CIH环境下,NE组每日给予依达拉奉注射液(3mg/kg)尾静脉注射,NS组给予0.9%生理盐水(3mg/kg)尾静脉注射。实验结束后,取各组大鼠肺组织标本,观察肺组织病理变化、应用免疫组化检测肺组织ACE2蛋白的表达,丙二醛(NDA)测定试剂盒检测MDA水平、实时荧光定量PCR法检测ACE2mRNA、血管紧张素Ⅱ(AngⅡ)mRNA的表达。结果 UC组未见明显病理损害,而CIH组及NS组肺泡壁水肿增厚,肺泡萎缩不张,肺间质及支气管上皮内也可见中性粒细胞浸润,且随时间延长病理损伤逐渐加重,与NS相比NE组出现病理损伤的时间较晚且程度较轻;与UC组比较,CIH组及NS组MDA含量、AngⅡmRNA表达在观察时间点内均逐渐增加(P<0.05),于4周达到高峰;而ACE2蛋白及ACE2mRNA1周、2周呈逐渐增高趋势(P<0.05),于2周时达到峰值,然后逐渐下降(P<0.05);与NS组比较,NE组各指标升高幅度较低,依达拉奉能抑制CIH引起的各指标的的增加(P<0.05);CIH组肺组织AngⅡmRNA水平与MDA含量均呈正相关(r=0.782,P<0.01)。结论提示ACE2对慢性间歇低氧大鼠肺组织氧化应激损伤有一定的保护作用,其机理可能与对AngⅡ降解作用增强有关。
Objective To investigate the dynamic changes of angiotensin converting enzyme 2 (ACE2) in the lung tissue of chronic intermittent hypoxia (CIH) induced by oxidative stress and to explore its possible mechanism in CIH lung injury. Methods 96 Wistar rats were randomly divided into normal control group (UC group), CIH group, edaravone treatment group (NE group) and placebo (0.9% NaCl) treatment group (NS group) , 2 weeks, 3 weeks, 4 weeks 4 subgroups, 6 rats in each subgroup. UC group were exposed to the air, CIH group, NE group and NS group were exposed to CIH environment, NE group were given edaravone injection (3mg / kg) intravenous injection, NS group were given 0.9% saline 3mg / kg) tail vein injection. After the experiment, take the lung tissue samples of each group to observe the pathological changes of the lung tissue. The expression of ACE2 protein in the lung tissue was detected by immunohistochemistry. The MDA level was detected by the NDA kit. The real-time PCR ACE2 mRNA and Ang Ⅱ mRNA expression. Results There was no obvious pathological damage in UC group, while the alveolar wall edema in CIH group and NS group were thicken, alveolar atrophy was atelectasis, neutrophil infiltration was also seen in interstitial lung and bronchial epithelium, and the pathological injury was aggravated with time. Compared with NS group, pathological injury of NE group was late and mild. Compared with UC group, the content of MDA and the expression of Ang Ⅱ mRNA in CIH group and NS group increased gradually at the time point of observation (P <0.05) (P <0.05), and peaked at 2 weeks, then decreased gradually (P <0.05). Compared with NS group, the increase of each index of NE group In the CIH group, there was a positive correlation between the level of AngⅡmRNA and MDA content (r = 0.782, P <0.01). The results suggest that ACE2 may play a protective role in the oxidative stress injury of lungs in chronic intermittent hypoxic rats. The mechanism may be related to the enhancement of AngⅡ degradation.