摘要
目的探讨供、受者在肺移植前后吸入低浓度一氧化氮(NO)对移植肺缺血/再灌注损伤的影响及其机制。方法取60只雄性SD大鼠,随机配对建立左肺移植模型。实验分为2组,NO组：获取供肺前,供者在移植肺灌洗期吸人体积分数为0．001%的NO；肺移植后,受者在移植肺再灌注后10min～2h持续吸入相同浓度的NO。对照组：供、受者肺移植前后不做任何特殊处理,只进行肺移植。供者开胸时及受者再灌注2h后,分别夹闭右肺门5min,进行动脉血气分析检测。受者术前及再灌注后2h时分别检测肺功能和动脉血气分析。再灌注2h后,取移植肺组织测髓过氧化物酶(MPO)活性、丙二醛(MDA)含量、肺湿/干重比(W/D)以及诱生型一氧化氮合酶(iNOS)的活性及其mRNA表达,并观察移植肺的病理学形态。结果移植肺再灌注2h后,NO组动脉血氧分压/吸氧浓度(PaO_2/FiO_2)值较对照组升高,氧合指数(OI)值、肺内分流(Qs/Qt)值较对照组降低,两组相比,差异有统计学意义(P均＜0．05)。NO组与对照组相比,MPO活性明显降低,MDA含量明显增高,W/D无显著差异。NO组iNOS蛋白活性及其mRNA表达均较对照组显著降低,iNOS主要表达在肺泡上皮细胞、肺泡腔和间质内浸润的炎症细胞。NO组炎症细胞浸润明显较对照组轻。结论供、受者在肺移植前后吸入低浓度NO能改善移植肺的氧合、减轻缺血/再灌注损伤,其机制可能与NO减少肺内分流、下调iNOS表达以及减轻肺内炎症细胞浸润有关。
Objective To investigate the effects of inhaled low dose nitric oxide （NO） on lung ischemia-reperfusion injury during flush and delayed 10 rain after reperfusion. Methods Sixty health adult male Sprague-Dawley rats were randomly allocated to the control and the NO group. Before the donor lung was harvested, the right hilus was clipped for 5 min （clipping test）, then blood sample was collected from carotid artery for arterial blood gas analysis as baseline. Lung transplantation was performed in a ＂cuff-like＂ vessel anastomosis technique. Dynamic compliance （Cdyn） and resistance of airway （Raw） were monitored before operation （baseline） and after 2 h reperfusion. The graft＇s gas exchange and oxygenation were assessed by ＂clipping test＂ after 2-h reperfusion. The lung graft was harvested for measuring wet/dry weight ratio （W/D）, the activity of myeloperoxidase （MPO） and inducible nitric oxide synthase （iNOS）, the content of malonyldialdehyde （MDA）, and the expression of iNOS gene and protein. Results After 2-h reperfusion, compared to the control group, PaO2/FiO2, OI, and Qs/Qt were improved significantly in the NO group （277 ± 91 vs. 157 ± 47, P〈0. 01 ; 2. 67 ±0. 89 vs. 4. 72± 1.48, P〈0. 01 ; 21. 1±4. 57 vs. 27. 1 ±2. 37, P〈0. 01, respectively）. The activities of MPO were significantly reduced in NO group （ 1.80 ± 0. 46 vs 3.08 ± 0. 65 U/g tissue, P〈0. 01 ）. The content of MDA in the lung tissue of NO group was significantly higher than that of the control group （34. 8 ± 7. 9 vs. 20. 0 ± 11.2 nmol/mg protein, P〈0. 05）. Inflammatory cell infiltration was also significantly reduced （P〈0. 05）. The expression of iNOS gene and protein in the lung tissue of NO group was significantly lower than that of the control group. The activities of iNOS were also significantly reduced in NO group （ 10. 6 ± 10. 2 vs 97. 8 ± 82. 2 nmol· g^-1· min^- 1 , P〈0. 05 ）. The im munohistochemical positive staining of iNOS was localized in the alveolar epithelial cells and the inflammatory cells infiltrated in the alveolar spaces and mesenchymal tissue. But there were no significant differences between two groups in Cdyn, Raw and W/D ratio. Conclusion Inhaled low dose NO might mitigate the intrapulmonary shunt, prevent neutrophil sequestration, inhibit the expression of iNOS gene and protein in isograft, thereby ameliorate ischemia-reperfusion injury and improve the oxygenation of the graft.
出处
《中华器官移植杂志》
CAS
CSCD
北大核心
2006年第10期599-602,共4页
Chinese Journal of Organ Transplantation
关键词
一氧化氮
肺移植
再灌注损伤
大鼠
Nitric oxide
Lung transplantation
Reperfusion injury
Rat
