Worrall N K, Boasquevisque C H, Misko T P, Sullivan P M, Ferguson T B, Patterson G A
Department of Surgery, Washington University School of Medicine, St. Louis, Missouri, USA.
J Heart Lung Transplant. 1997 Mar;16(3):334-9.
We recently demonstrated that inhibition of nitric oxide (NO) production ameliorated acute pulmonary allograft rejection. This study examined whether inducible NO synthase (iNOS) was expressed in the transplanted lung during acute rejection.
With a rat left lung transplant model, tissue from syngeneic (Fischer 344 to Fischer 344) and allogeneic (Brown Norway to Fischer 344) transplants were harvested on postoperative day 4 and analyzed for iNOS mRNA expression (ribonuclease protection assay), iNOS enzyme activity (conversion of L-[3H]-arginine to NO and L-[3H]-citrulline), and serum nitrite/nitrate levels.
The iNOS mRNA was expressed in allograft lungs but was not detected in isografts or controls. The iNOS protein was present in allograft lungs, as demonstrated by high levels of L-[3H]-citrulline production compared with minimal iNOS enzyme activity in isograft and control lungs (10.1 +/- 2.4 vs 0.6 +/- 0.2 and 0.7 +/- 0.2 pmol L-[3H]-citrulline.mg-1.min-1, respectively; n = 6, p < 0.001). Allografts had significantly elevated systemic serum nitrite/nitrate levels compared with isografts and controls (38 +/- 6 vs 18 +/- 2 and 16 +/- 1 mumol/L, respectively; n = 6; p < 0.005).
These results, together with our previous demonstration that iNOS inhibition ameliorated lung allograft rejection, suggest that (1) iNOS expression and increased NO production contributed to acute rejection of the transplanted lung, (2) iNOS inhibition may offer an alternative in management of acute lung allograft rejection, and (3) increased NO production, detected by the presence of iNOS mRNA or protein or noninvasively by measuring serum nitrite/nitrate levels, may serve as an early marker of acute allograft rejection.
我们最近证明抑制一氧化氮（NO）生成可改善急性肺移植排斥反应。本研究检测了急性排斥反应期间移植肺中是否表达诱导型一氧化氮合酶（iNOS）。
采用大鼠左肺移植模型，在术后第4天采集同基因（Fischer 344到Fischer 344）和异基因（Brown Norway到Fischer 344）移植的组织，分析iNOS mRNA表达（核糖核酸酶保护分析）、iNOS酶活性（L-[3H]-精氨酸转化为NO和L-[3H]-瓜氨酸）以及血清亚硝酸盐/硝酸盐水平。
iNOS mRNA在移植肺中表达，但在同基因移植肺或对照中未检测到。iNOS蛋白存在于移植肺中，与同基因移植肺和对照肺中极低的iNOS酶活性相比，移植肺中L-[3H]-瓜氨酸生成水平较高（分别为10.1±2.4与0.6±0.2和0.7±0.2 pmol L-[3H]-瓜氨酸·mg-1·min-1；n = 6，p < 0.001）。与同基因移植肺和对照相比，异基因移植肺的全身血清亚硝酸盐/硝酸盐水平显著升高（分别为38±6与18±2和16±1 μmol/L；n = 6；p < 0.005）。
这些结果，连同我们之前证明的iNOS抑制可改善肺移植排斥反应，表明（1）iNOS表达和NO生成增加促成了移植肺的急性排斥反应，（2）抑制iNOS可能为急性肺移植排斥反应的治疗提供一种替代方法，（3）通过iNOS mRNA或蛋白的存在或通过测量血清亚硝酸盐/硝酸盐水平进行非侵入性检测到的NO生成增加，可能作为急性移植排斥反应的早期标志物。
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