Analyses of the process to the chronic rejection after rat lung trasplantation.

【背景与目的】慢性排斥反应是肺移植术后中远期死亡的主要原因。其机制尚不清楚，但不少数据表明，急性排斥反应的频率和严重程度是移植后阻塞性支气管炎的危险因素，被认为是慢性排斥反应的表现。因此，早期发现和治疗急性排斥反应非常重要。据报道，在心脏或胰腺移植后，一氧化氮（NO）的产生会随着急性排斥反应而急剧增加。我们假设肺移植后NO的产生也是急性排斥反应的一个标志，并研究了大鼠肺移植后呼出空气中的NO和支气管肺泡细胞中的NO的产生。【材料、方法及结果】实验1(1995-1996)：三组大鼠原位肺移植中，同种异体（Brown-Norway to Lewis）。移植后第3天、第5天测定呼出空气中no的孔隙蛋白和等基因（Lewis to Lewis）。第3天各组呼出空气NO含量差异无统计学意义，但第5天同种异体+无治疗组（63.9 * 39.2 ppb）明显高于同种异体+环孢素组（9.1 * 1.6）和等基因组（6.9 * 0.5）。此外，呼出空气中NO与急性排斥反应的组织学分级显著相关（p< 0.01）。实验二（1996-1997）：在两组大鼠原位肺移植中，分别测定同种异体(Brown-Norway to Lewis) +未处理、等基因（Lewis to Lewis），分别于移植后第3天、第5天对经支气管肺泡灌洗培养3小时的细胞进行no生成，并对细胞进行iNOS免疫染色。与异体组（未检测到）相比，等基因组在第3天（11.6 * 2.5 ppb）和第5天（195.4 * 154.7 ppb）的NO产量显著（p< 0.01）高。巨噬细胞、淋巴细胞和中性粒细胞均进行iNOS染色。【结论及意义】呼出空气NO是肺移植术后急性排斥反应的敏感指标，BAL细胞NO的产生也是或更敏感的指标。少

[Background and Purpose] Chronic rejection is the major cause of death intermediate- or long-term after lung transplantation. Its mechanism remains to be clearly demonstrated, but not a few data have shown that the frequency and severity of acute rejection are the risk factors for post-transplantation obstructive bronchitis considered as a manifestation of chronic rejection. Accordingly early detection and treatment of acute rejection is very important. After heart or pancreas transplantation, nitric oxide (NO) production have been reported to increase dramatically in accordance with acute rejection. We hypothesized that also after lung transplantation NO production would be a marker of acute rejection and investigated NO in exhaled air and NO production from bronchoalveolar cells after rat lung transplantation.[Material, Method and Results]Experiment 1(1995-1996) :In the 3 groups of orthotopic rat lung transplantation, allogenic (Brown-Norway to Lewis). +no treatment, allogenic+cyclos … More porin and isogenic (Lewis to Lewis), NO in exhaled air was determined on days 3, 5 after transplantation. NO in exhaled air were not different among the three groups on day 3, but on day 5 significantly (p<.Ol) high in the allogenic + no treatment group (63.9 * 39.2 ppb) compared with the allogenic+cyclosporin group (9.1 * 1.6) and isogenic group (6.9 * 0.5). Furthermore NO in exhaled air was significantly (p<.Ol) correlated with histological grading of acute rejection.Experiment 2(1996-1997) :In the 2 groups of orthotopic rat lung transplantation, allogenic (Brown-Norway to Lewis) + no treatment, isogenic (Lewis to Lewis), NO production from the cells collected by bronchoalveolar lavage and incubated for 3 hours was determined on days 3, 5 after transplantation, and also those cells were immunostained for iNOS.NO production was significantly (p<.Ol) high in the isogenic group (11.6 * 2.5 ppb) compared with the allogenic group (not detected) on day 3, and furthermore on day 5 (195.4 * 154.7 ppb). iNOS was stained on the recovered macrophages, lymphocytes and neutrophils.[Conclusion and Implication] NO in exhaled air would be a sensitive marker of acute rejection after lung transplantation, and furthermore NO production from the BAL cells would be also or more sensitive marker. Less