内皮素受体拮抗剂对肺移植凋亡及一氧化氮合酶II表达的影响。

Effect of endothelin receptor antagonist on lung allograft apoptosis and NOSII expression.

作者信息

Shaw M J, Shennib H, Bousette N, Ohlstein E H, Giaid A

机构信息

Department of Surgery, The Montreal General Hospital, McGill University, Quebec, Canada.

出版信息

Ann Thorac Surg. 2001 Aug;72(2):386-90. doi: 10.1016/s0003-4975(01)02792-8.

DOI:10.1016/s0003-4975(01)02792-8

PMID:11515871

Abstract

BACKGROUND

It is postulated that apoptosis contributes to ischemia-reperfusion graft dysfunction after lung transplantation. The purpose of this study was to determine whether the improvement in lung function that we previously observed with the use of an endothelin-1 (ET-1) receptor antagonist after ischemia-reperfusion injury is associated with a reduction in inducible nitric oxide synthase (NOSII) expression and programmed cell death.

METHODS

Left lung canine allotransplantation was performed. Harvested lung blocks were preserved with modified Eurocollins solution and stored at 4 degrees C for 18 to 20 hours. Lung allografts were tested for the expression of NOSII by immunohistochemistry, and extent of apoptosis by terminal dUTP nick end-labeling (TUNEL). Animals blindly received either an intravenous infusion of saline (control) or the ET-1 receptor antagonist (SB209670) (15 microg/kg/min). Infusion began 30 minutes pretransplantation and continued to 6 hours posttransplantation.

RESULTS

Immunohistochemical analysis demonstrated significantly stronger NOSII immunostaining in the allografts of the saline control group (36.5%+/-3.6%) compared with native right lungs (6.9%+/-1.3%, p < 0.001) or the ET-receptor antagonist treatment group (9.6%+/-1.4%, p < 0.001). The TUNEL staining revealed a significantly stronger labeling in the allografts of the saline treatment control group (40.7%+/-6.2%) compared with native right lungs (5.0%+/-0.6%, p < 0.005) or the ET receptor antagonist treatment group (14.1%+/-2.8%, p < 0.01).

CONCLUSIONS

We conclude that treatment of lung allografts with the ET-1 receptor antagonist SB209670 reduces the area of NOSII expression and the extent of apoptosis, factors known to contribute to the process of prolonged ischemia-reperfusion injury.

摘要

背景

据推测，细胞凋亡导致肺移植后缺血再灌注移植功能障碍。本研究的目的是确定我们之前观察到的在缺血再灌注损伤后使用内皮素-1（ET-1）受体拮抗剂后肺功能的改善是否与诱导型一氧化氮合酶（NOSII）表达的减少和程序性细胞死亡有关。

方法

进行左肺犬同种异体移植。收获的肺块用改良的Eurocollins溶液保存，并在4℃下储存18至20小时。通过免疫组织化学检测肺同种异体移植中NOSII的表达，并通过末端脱氧核苷酸转移酶介导的缺口末端标记法（TUNEL）检测细胞凋亡程度。动物被随机分为静脉输注生理盐水（对照组）或ET-1受体拮抗剂（SB209670）（15微克/千克/分钟）。输注在移植前30分钟开始，并持续至移植后6小时。

结果

免疫组织化学分析显示，与天然右肺（6.9%±1.3%，p<0.001）或ET受体拮抗剂治疗组（9.6%±1.4%，p<0.001）相比，生理盐水对照组同种异体移植中的NOSII免疫染色明显更强（36.5%±3.6%）。TUNEL染色显示，与天然右肺（5.0%±0.6%，p<0.005）或ET受体拮抗剂治疗组（14.1%±2.8%，p<0.01）相比，生理盐水治疗对照组同种异体移植中的标记明显更强（40.7%±6.2%）。