半胱氨酸蛋白酶3和白细胞介素8在高氧暴露下早产大鼠肺组织中的动态表达及其意义

目的 探讨半胱氨酸蛋白酶-3(Caspase-3)及白细胞介素-8(IL-8)在早产大鼠高氧肺损伤中的动态表达及其意义.方法 孕21 d的SD早产大鼠生后第2天,随机分为空气组和高氧组(均n=40).高氧组大鼠予以85%高氧持续暴露,空气组大鼠置于空气中.于暴露1、4、7、14和21 d每组各处死8只大鼠,收集肺组织标本,苏木精-伊红染色观察肺组织病理形态学变化,双抗夹心ELISA法检测IL-8含量,免疫组化和Western blot检测Caspase-3表达.结果 高氧暴露后肺泡腔内可见有坏死脱落细胞、炎症细胞渗出增多、间质水肿,肺组织结构紊乱,肺泡形成明显滞后,肺泡结构简单化和囊泡化;与空气对照组比较,高氧暴露4、7和14 d肺组织Caspase-3和IL-8含量均明显增高(P＜0.01).结论 在高氧所致早产大鼠肺损伤中细胞凋亡和坏死共存,两者共同参与了早产大鼠高氧肺损伤的病理过程.

Temporal expression and significance of caspase-3 and interleukin-8 in the lungs of preterm rats exposed to hyperoxia

Objective To explore the temporal expression and significance of Caspase-3 and interleukin-8(IL-8) in hyperoxia-induced lung injury in preterm rats.Methods Two-day-old Sprague-Dawley preterm rats were randomly divided into Air group and Hyperoxia group (each rats in each group).Rats in the Hyperoxia group were exposed to 85% O2,while rats in the Air group were exposed to air.The rats in each group were sacrificed at 1,4,7,14 and 21 days after exposure (8 rats at each time point),and lung tissues were collected.Pathomorphology of lungs was observed by hematoxylin-eosine staining.The contents of IL-8 in the homogenate of lungs were detected using ELISA.The expression of Caspase-3 was detected by immunohistochemistry and Western blot.Results (1) Lung histopathology:after hyperoxia exposure 1 day,no significant effects on alveoli were found;but on days 4 and 7,alveolitis appeared:there were necrotic abscission cells in alveolar space,increased inflammatory cells infiltration,lung interstitial edema;on days 14 and 21,lung structure derangement,decreased number of alveoli,simplified and vesicular lung structure,all of which showed the retardation of alveolar formation.(2) the contents of IL-8 in the homogenate of lungs had no significant change on day 1 but increased significantly on days 4,7 and 14 compared with air control group (P＜0.01 for all).(3) Immunohistochemistry detected the expression of Caspase-3 in the lung:the intensity of Caspase-3 expression increased significantly on days 4,7 and 14 compared with air control group(P＜0.01).(4) Western blotting detected the expression of caspase-3 in the lung:the pattern of dynamic expression of Caspase-3 was similar to the results of immunohistochemistry.Conclusions Both apoptosis and necrosis contribute to cell death during hyperoxia.Apoptosis and necrosis may both play an important role in hyperoxia-induced lung injury in preterm rats.