CAJ | 학술논문

目的:探讨血管生成素-2(Ang-2)及其受体具有免疫球蛋白和表皮生长因子同源性结构域的酪氨酸蛋白激酶-2(Tie-2)在大鼠急性肺损伤(ALI)时的表达及意义.方法:42只Wistar大鼠随机分为对照组12只,采用假手术处理;CLP组30只,采用盲肠结扎穿孔术(CLP)制作ALI模型,于假手术及CLP术后12 h每组各处死6只大鼠,进行动脉血气分析,取左肺计算肺系数,采用免疫组织化学法检测Tie-2及Ang-2在鼠肺组织中的表达,酶联免疫吸附试验检测血清Ang-2的水平,观察36 h内2组鼠死亡率.结果:光镜下对照组鼠肺组织结构清楚;CLP组肺泡间隔增厚,毛细血管充血水肿,有中性粒细胞及巨噬细胞浸润.对照组在支气管上皮细胞、平滑肌细胞及内皮细胞表达Tie-2;CLP组Tie-2表达与对照组相似外,中性粒细胞及巨噬细胞有强阳性表达,在Tie-2阳性的炎症细胞附壁区域,内皮细胞Tie-2表达亦增强.对照组Ang-2主要表达于平滑肌细胞、支气管上皮细胞及内皮细胞,CLP组Ang-2在炎症渗出区的巨噬细胞表达增强,其它与对照组相似.CLP组血清Ang-2水平(8.14±1.74)μg/L明显高于对照组(4.63±0.49)μg/L(P<0.01),且CLP组36 h内死亡鼠Ang-2血清水平(8.95±1.61)μg/L显著高于存活鼠(6.80±0.96)μg/L(P<0.01);CLP组动脉血氧分压低于对照组(P<0.01),肺系数则高于对照组(P<0.01).结论:Ang-2与Tie-2可能参与ALI的发病过程,Ang-2血清水平增高与预后有关.
목적:탐토혈관생성소-2(Ang-2)급기수체구유면역구단백화표피생장인자동원성결구역적락안산단백격매-2(Tie-2)재대서급성폐손상(ALI)시적표체급의의.방법:42지Wistar대서수궤분위대조조12지,채용가수술처리;CLP조30지,채용맹장결찰천공술(CLP)제작ALI모형,우가수술급CLP술후12 h매조각처사6지대서,진행동맥혈기분석,취좌폐계산폐계수,채용면역조직화학법검측Tie-2급Ang-2재서폐조직중적표체,매련면역흡부시험검측혈청Ang-2적수평,관찰36 h내2조서사망솔.결과:광경하대조조서폐조직결구청초;CLP조폐포간격증후,모세혈관충혈수종,유중성립세포급거서세포침윤.대조조재지기관상피세포、평활기세포급내피세포표체Tie-2;CLP조Tie-2표체여대조조상사외,중성립세포급거서세포유강양성표체,재Tie-2양성적염증세포부벽구역,내피세포Tie-2표체역증강.대조조Ang-2주요표체우평활기세포、지기관상피세포급내피세포,CLP조Ang-2재염증삼출구적거서세포표체증강,기타여대조조상사.CLP조혈청Ang-2수평(8.14±1.74)μg/L명현고우대조조(4.63±0.49)μg/L(P<0.01),차CLP조36 h내사망서Ang-2혈청수평(8.95±1.61)μg/L현저고우존활서(6.80±0.96)μg/L(P<0.01);CLP조동맥혈양분압저우대조조(P<0.01),폐계수칙고우대조조(P<0.01).결론:Ang-2여Tie-2가능삼여ALI적발병과정,Ang-2혈청수평증고여예후유관.
AIM: To explore the expressions and significance of angiopoietin-2 (Ang-2) and tyrosine kinase with immunoglobulin and epidermal growth factor homology domains-2 (Tie-2) receptors in a rat model of acute lung injury (ALI). METHODS: Wistar rats (n=42) were divided into control group (n=12) and cecal ligation and puncture (CLP) group (n=30). Control group underwent sham operation, and CLP group underwent cecal ligation and puncture to make the model of ALI. 12 h after sham operation or CLP, 6 rats in each group were killed, and arterial blood gas analysis and lung coefficient were tested. The expressions of Ang-2 and Tie-2 receptors in lung tissue were observed by immunohistochemical method. Blood samples of the rest rats were collected from vena caudalis, and Ang-2 levels were measured by enzyme linked immunosorbent assay (ELISA). The mortality rate in each group within 36 h was compared. The lung architecture was observed under microscope. RESULTS: The lung architecture in control group was clear and intact. Alveolar septum was thicker, blood capillary was congested, and neutrophils and macrophages were infiltrated in the lung tissue in CLP group. Tie-2 receptors were expressed in bronchial epithelial cells, smooth muscle cells and endothelial cells in control group. Besides the similar expression as control group, high expression of Tie-2 on neutrophils and macrophages in CLP group was observed. In the adhesion location of Tie-2 receptors positive inflammatory cells, there was stronger staining in endothelial cells. Ang-2 was expressed in smooth muscle cells, bronchial epithelial cells and endothelial cells in control group. The Ang-2 level in CLP group were higher than that in control group [(8.14±1.74) μg/L vs (4.63±0.49) μg/L, P<0.01], and the Ang-2 level of dead rats was higher than that of survival rats within 36 h in CLP group [(8.95±1.61)μg/L vs (6.80±0.96)μg/L, P<0.01]. Oxygen partial pressure in control group was lower (P<0.01) and lung coefficient was higher (P<0.01) than that in CLP group. CONCLUSION: Ang-2 and Tie-2 receptors may participate in the pathophysiology of ALI, and Ang-2 level is correlated with mortality.