CAJ | 학술논문

目的观察-氧化碳释放分子(CORM)-2对大鼠肢体缺血-再灌注(I/R)所致肺损伤的作用及分子机制.方法复制大鼠双后肢缺血及再灌注后肺损伤模型.将40只SD大鼠,随机(随机数字法)分为5组(每组n=8):假手术组(sham)、sham+ CORM-2组、I/R组、I/R+ CORM-2组、I/R+ DMSO(二甲亚砜)组.观察大鼠肺组织学、中性粒细胞(PMN)数目、肺组织湿重/干重(W/D)、丙二醛(MDA)含量、髓过氧化物酶(MPO)活性、细胞间黏附分子-1(ICAM-1)、核因子-κB (NF-κB)及其抑制因子IκBα的变化.结果 IR组肺组织中PMN数目、W/D、MDA含量、MPO活性、ICAM-1表达、NF-κB活性均显著高于sham组,IκBα表达降低；再灌注前应用CORM-2可以明显逆转动物上述指标的变化,使肺损伤减轻.结论 CORM-2通过抑制肢体I/R后肺内IκBα降解和NF-κB激活,下调ICAM-1表达和PMN肺内扣押,从而发挥抗肢体IR所致肺损伤的作用.
목적 관찰-양화탄석방분자(CORM)-2대대서지체결혈-재관주(I/R)소치폐손상적작용급분자궤제.방법 복제대서쌍후지결혈급재관주후폐손상모형.장40지SD대서,수궤(수궤수자법)분위5조(매조n=8):가수술조(sham)、sham+ CORM-2조、I/R조、I/R+ CORM-2조、I/R+ DMSO(이갑아풍)조.관찰대서폐조직학、중성립세포(PMN)수목、폐조직습중/간중(W/D)、병이철(MDA)함량、수과양화물매(MPO)활성、세포간점부분자-1(ICAM-1)、핵인자-κB (NF-κB)급기억제인자IκBα적변화.결과 IR조폐조직중PMN수목、W/D、MDA함량、MPO활성、ICAM-1표체、NF-κB활성균현저고우sham조,IκBα표체강저；재관주전응용CORM-2가이명현역전동물상술지표적변화,사폐손상감경.결론 CORM-2통과억제지체I/R후폐내IκBα강해화NF-κB격활,하조ICAM-1표체화PMN폐내구압,종이발휘항지체IR소치폐손상적작용.
Objective To observe the role and mechanism of CO-releasing molecules (CORMs) -2in the injured lung induced by ischmia-reperfusion (IR) of hind limbs of rat.Methods The rat model of lung injury was made by ischemia in hind limbs of rat for two hours and then reperfusion for two hours as well.There were 40 SD rats randomly ( random number) divided into 5 groups ( n =8 ),namely sham ischemia-reperfusion (I/R) group,sham I/R + CORM-2 group,I/R group,I/R + CORM-2 group and I/R + DMSO (Dimethylsulfoxide) group. Rats in sham I/R group underwent laparotomy without infrarenal aorta occlusion.The lung tissue structure,polymorphonuclear neutrophil (PMN) count,wet-to-dry weight ratio (W/D), malondialdehyde (MDA) content, myeloperoxidase (MPO) activity, intercellular adhesion molecule-1 ( ICAM-1 ),nuclear IκBα degradation and NF-κB activity in the lung were measured.Results Compared with the sham I/R group,the number of PMNs in lung,W/D,MDA content,MPOactivity,ICAM-1 and NF-κB activity significantly increased in I/R group,whereas nuclear IκBα decreased (P ＜ 0.01).Compared with the I/R group,the number of PMNs in lung,W/D,MDA content,MPO activity and ICAM-1 significantly decreased in I/R + COMR-2 group ( P ＜ 0.01 ), while nuclear IkBαincreased. Conclusions These data demonstrate that CORM-2 attenuates limb I/R-induced lung injury by inhibiting ICAM-1 protein,NF-κB pathway and the leukocytes sequestration in the lung following limb I/R in rats,suggesting that CORM-2 could be used as one of the most valuable therapeutic agents.