Bacterial translocation during graft-versus-host disease after small bowel transplantation is reduced following inhibition of inducible nitric oxide synthesis.
Bacterial translocation during graft-versus-host disease after small bowel transplantation is reduced following inhibition of inducible nitric oxide synthesis.
复制标题
抑制诱导型一氧化氮合成后，小肠移植后移植物抗宿主病期间的细菌易位减少。
作者：
J. Langrehr;C. Machens;Edith Zill;K. Leder;Andreas N??ssler;Rosemary A. Hoffman;Peter Neuhaus
背景
一氧化氮（NO）的产生增加可能导致肠屏障功能障碍和细菌移位（BT）增加。由于BT可能在小肠移植（SBTx）后的移植物抗宿主病（GVHD）中发挥重要作用，我们评估了大鼠SBTx后NO产生在GVHD中的作用。
方法
使用大鼠半同种异体SBTx的标准模型，我们准备了三个实验组。第1组受体接受LBNF 1-LBNF 1移植并接受氨基胍（AG）（200 mg/kg）治疗，第2组受体接受Lewis-LBNF 1移植并注射生理盐水，第3组受体接受Lewis-LBNF 1移植和AG（200 mg/kg）。每天测量尿亚硝酸盐/硝酸盐水平，通过培养腹膜拭子、肠系膜淋巴结、脾、肝和血液确定BT。
结果
在第1组中，我们检测到无限期生存与正常组织学。在第2组中，存活期达到10.5 +/- 1.1天，并观察到急性GVHD的典型组织学特征。第3组动物的平均存活时间为14.8 +/- 0.6天（与第2组相比P<0.02），具有急性GVHD的组织学特征，尽管时间进程延长。术后第2、3天NO生成量和BT均显著低于对照组（P<0.03），术后第3、9天BT显著低于对照组（P<0.03）。
结论
用AG抑制诱导型NO合成减少了NO产生，降低了BT，并在SBTx后的GVHD期间降低了存活率，因此可能是对GVHD标准治疗方案的有用补充。
BACKGROUND
Increased nitric oxide (NO) production may contribute to intestinal barrier dysfunction and increased bacterial translocation (BT). Since BT may play a major role in graft-versus-host disease (GVHD) after small bowel transplantation (SBTx), we evaluated the role of NO production in GVHD after SBTX in the rat.
METHODS
Using the standard model of semiallogeneic SBTx in the rat, we prepared three experimental groups. Recipients in group 1 received LBNF1-LBNF1 transplants and were treated with aminoguanidine (AG) (200 mg/kg), recipients in group 2 received Lewis-LBNF1 grafts and were injected with saline, and recipients in group 3 received Lewis-LBNF1 transplants and AG (200 mg/kg). Urine nitrite/nitrate levels were measured daily, and BT was determined by culturing peritoneal swabs, mesenteric lymph nodes, spleen, liver, and blood.
RESULTS
In group 1 we detected indefinite survival with normal histology. In group 2 a survival of 10.5 +/- 1.1 days was reached, and the typical histological features of acute GVHD were observed. The animals in group 3 showed a mean survival of 14.8 +/- 0.6 days (P<0.02 compared with group 2) and the histological features of acute GVHD, although with a prolonged time course. Comparing NO production and BT between groups 2 and 3 we detected significantly reduced NO production on postoperative days 2-9 (P<0.03) and significantly decreased BT on postoperative days 3 and 9 (P<0.03).
CONCLUSION
Inhibition of inducible NO synthesis with AG reduces NO production, decreases BT, and prolongs survival during GVHD after SBTx and therefore may be a useful addition to standard treatment protocols for GVHD.
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通过电子顺磁共振波谱法检测大鼠小肠移植后排斥反应和移植物抗宿主病期间的一氧化氮。
影响因子：
3.8
作者：
Langrehr,JM;Muller,AR;Bergonia,HA;Jacob,TD;Lee,TK;Schraut,WH;LancasterJr,JR;Hoffman,RA;Simmons,RL
通讯作者：
Simmons,RL
抑制诱导型一氧化氮合酶可改善急性肺同种异体移植排斥的功能和组织学变化。
影响因子：
6.2
作者：
Worrall,NK;Boasquevisque,CH;Botney,MD;Misko,TP;Sullivan,PM;Ritter,JH;FergusonJr,TB;Patterson,GA
通讯作者：
Patterson,GA
DOI：
10.1152/ajpgi.1995.268.2.g361
发表时间：
1995-02-01
影响因子：
4.5
作者：
SALZMAN, AL;MENCONI, MJ;FINK, MP
通讯作者：
FINK, MP
影响因子：
29.4
作者：
Unno, N;Wang, HL;Fink, MP
通讯作者：
Fink, MP
小鼠移植物抗宿主病期间宿主淋巴组织的旁观者损伤是由一氧化氮介导的。
影响因子：
6.2
作者：
Hoffman,RA;Langrehr,JM;Berry,LM;White,DA;Schattenfroh,NC;McCarthy,SA;Simmons,RL
通讯作者：
Simmons,RL