黏膜上皮趋化因子28表达与肺移植术后急性肺损伤的关系

Relationship between C-C motif chemokine ligand 28 expression and acute lung injury after lung transplantation

目的:探讨黏膜上皮趋化因子28(CCL28)与肺移植术后急性肺损伤发生的关系。方法:高通量筛选低氧条件下人肺毛细血管内皮细胞(PCEC)mRNA-CCL28高表达,同时检测肺移植术后患者血清以及肺移植小鼠肺组织mRNA-CCL28表达。观察低氧条件下PCEC培养基趋化人单核细胞(THP-1)的作用;利用腺病毒携带CCL28转染动物模型,观察过表达CCL28对肺移植小鼠炎性因子及肺损伤的影响。多组比较采用方差分析,术前及术后数据采用配对t检验。结果:肺移植术后血清CCL28表达高于术前,0.970±0.100比0.766±0.148,t=-3.217,P<0.05;经PCR检测,术后mRNA-CCL28高于术前(2.438±0.210比1.000±0.088),t=-17.844,P<0.05;低氧条件下PCEC培养基趋化THP-1,低氧组迁移细胞高于对比组(252.000±20.662比140.670±12.662),t=-7.957,P<0.05;过表达CCL28使支气管灌洗液内肿瘤坏死因子-α(TNF-α)(231.17±22.27)、白细胞介素(IL)-1β(92.81±11.44)和IL-6(317.14±39.14)分别与移植组TNF-α(184.84±14.38)、IL-1β(74.57±9.63)、IL-6(252.22±29.03)比较,表达水平高于移植组,同时过表达CCL28加重肺损伤。结论:低氧条件下CCL28高表达并趋化THP-1加重肺移植术后急性炎性反应以及肺损伤。

Objective To investigate the relationship between C-C motif chemokine ligand 28(CCL28)and acute lung injury after lung transplantation.Methods High throughput screening was performed for determining mRNA-CCL28 expression in human primary pulmonary capillary endothelial cells(PCEC)under the hypoxia condition.The CCL28 expression in patients and rat lung tissue after lung transplantation was detected.The chemotactic effect on THP-1 by PCEC medium under the hypoxia condition was observed by co-culture system.The effects of overexpression of CCL28 on inflammatory factors and lung injury were observed in animal models transfected with adenovirus carrying CCL28.One way analysis of variance was applied to determine statistical significance among multiple groups.Data collected before and after surgery were analyzed with paired t-test.Results The expression of CCL28 in serum after lung transplantation was higher than that before surgery(0.970±0.100 vs.0.766±0.148,t=-3.217,P<0.05).The PCR results showed that mRNA-CCL28 was significantly higher after operation than that before operation(2.438±0.210 vs.1.000±0.088,t=-17.844,P<0.05).The number of migrating THP-1 cells in hypoxia group was significantly higher than that in control group(252.000±20.662 vs.140.670±12.662,t=-7.957,P<0.05).Overexpression of CCL28 increased the expression of tumor necrosis factor-α(TNF-α)(231.17±22.27),interleukin(IL)-1β(92.81±11.44)and IL-6(317.14±39.14)in bronchial lavage fluid as compared with that in transplantation group[TNF-α:(184.84±14.38);IL-1β:(74.57±9.63);and IL-6(252.22±29.03)].Meanwhile,overexpression of CCL28 aggravated acute lung injury.Conclusion The expression of CCL28 increased under the hypoxia condition,which induced THP-1 chemotactic migration and aggravated the inflammation and acute lung injury.