一氧化碳释放分子3通过抑制肺泡上皮细胞凋亡减轻脂多糖诱导的新生鼠急性肺损伤

目的 探讨一氧化碳释放分子3(CORM3)对脂多糖(LPS)诱导的新生鼠急性肺损伤(ALI)肺泡上皮细胞凋亡的影响。 方法 32只新生SD大鼠均分为对照组、LPS组、CORM3组和失活CORM3（iCORM3）组；LPS组、CORM3组和iCORM3组采用LPS气管内滴注建立新生鼠ALI模型，分别腹腔注射生理盐水、CORM3和iCORM3；对照组不建立ALI模型，腹腔注射生理盐水。于建模后12 h取肺组织，苏木素 伊红染色观察肺组织病理改变，湿干(W/D)比值测定，肺泡灌洗液(BALF)细胞计数及蛋白含量测定。体外培养A549细胞，LPS诱导细胞凋亡。MTT检测细胞活性，Tunel染色观察组织、细胞凋亡变化。 结果 ①与对照组相比，LPS组肺组织形态结构明显紊乱，肺泡压缩，肺间质大量炎性细胞浸润；CORM3组肺组织形态结构基本正常，间质炎性细胞浸润少；iCORM3组见肺组织水肿及大量炎性细胞浸润。②与对照组相比，LPS组肺组织W/D比值、BALF细胞数及蛋白含量明显升高，肺泡上皮细胞凋亡率明显增多［(37.3±4.5)% vs (3.0±1.0)%］；A549细胞活力下降，凋亡率明显升高［(29.6±4.1)% vs (3.6±1.0)%］，差异均有统计学意义 （P<0.05）。CORM3组肺组织W/D比值、BALF细胞数和蛋白含量较LPS组显著下降，肺泡上皮细胞凋亡率减少［（19.3±4.6）%］；A549细胞活力回升，凋亡率［（15.3±4.5）%］明显降低，差异均有统计学意义 （P<0.05）。LPS组与iCORM3组间上述指标差异均无统计学意义。 结论 CO通过抑制肺泡上皮细胞凋亡减轻新生鼠ALI

CORM3 attenuates acute lung injury induced by LPS via inhibiting AECs apoptosis in neonatal rats

Objective To study the protective effects of CORM3 treatment on AECs apoptosis after LPS inducing acute lung injury in neonatal rats. Methods Thirty two SD neonate rats were divided equally into four groups, the control group, LPS group,CORM3 group and iCORM3 group. Neonate rat acute lung injury was induced by LPS intratracheal administration in LPS group, CORM3 group and iCORM3 group received treatment of itraperitoneal injection of saline, CORM3 and iCORM3 respectively. The control group received intraperitoneal injection of saline. Animals in each group were sacrificed after 12h modeling, the histopathologic changes were observed by H E staining, and lung tissue was seperated and weighed, wet and dry ratio of lung tissue was calculated, lung tissue damage was detected by BALF cell counting and protein quantitative analysis. Cultivated A549 cell apoptosis was induced by LPS in vitro, cell activity was determined by MTT test, cell apoptosis was watched by Tunel dyeing. Results Firstly, compared with the control group, the morphological structure of lung tissue was disordered in model group, alveoli were compressed, and a lot of inflammatory cells in filtrated in pulmonary interstitium. CORM3 group kept basic normal morphological structure, and inflammatory cells infiltrated in alveolar interstitium were less, the iCORM3 group was consistent with the LPS group in lung morphological structure and inflammatory cells infiltration. Secondly, compared with the control group, the W/D ratio, BALF cell number and protein content increased significantly in LPS group, and the number of AECs apoptosis was increased obviously［(37.3±4.5)% vs (3.0±1.0)%］. The A549 cells activity was decreased, and percentage of apoptosis cells increased significantly［(29.6±4.1)% vs (3.6±1.0)%, P<0.05］,with a statistically significant difference. In CORM3 group compared with the LPS group, the W/D ratio, BALF cell number and protein content decreased obviously, and the number of AECs apoptosis was decreased［（19.3±4.6）%］. The A549 cells activity rebounded, and the rate of cells apoptosis［（15.3±4.5）%］ decreased significantly, the difference was statistically significant(P < 0.05).There were no significant changes between the iCORM3 group and the CORM3 group in these indexes. Conclusion CORM3 attenuates neonate rat acute lung injury induced by LPS via inhibiting AECs apoptosis.