CAJ | 학술논문

目的评价血红素氧合酶-1(HO-1)在远隔肢体缺血预处理减轻兔肺缺血再灌注损伤中的作用.方法日本大耳白兔24只,4～5月龄,体重2.0～2.5 kg,采用随机数字表法,将其分为4组(n=6):假手术组(S组)、缺血再灌注组(I/R组)、远隔肢体缺血预处理组(RLIP组)和HO-1抑制剂锌原卟啉+远隔肢体缺血预处理组(ZnPP+ RLIP组).采用结扎左肺门60 min、再灌注180 min的方法制备肺缺血再灌注损伤模型;结扎肺门前行后肢缺血预处理:双后肢缺血10 min,再灌注10 min,重复3次;ZnPP+ RLIP组后肢缺血预处理前10 min静脉注射锌原卟啉10μrmol/kg.于再灌注结束时,采集动脉血样,进行血气分析;取肺组织,光镜下观察病理学结果,进行肺损伤评分(LIS评分);测定肺组织湿/干重(W/D)比值、髓过氧化物酶(MPO)活性、丙二醛(MDA)含量、HO-1表达及其活性.结果与S组比较,I/R组PaO2降低,肺组织LIS评分、W/D比值、MPO活性、MDA含量、HO-1表达及其活性升高(P＜0.01);与I/R组比较,RLIP组PaO2、肺组织HO-1表达及其活性升高,肺组织LIS评分、W/D比值、MPO活性和MDA含量降低(P＜0.01);与RLIP组比较,ZnPP+ RLIP组PaO2、肺组织HO-1表达及其活性降低,肺组织LIS评分、W/D、MPO活性和MDA含量升高(P＜0.01).结论远隔肢体缺血预处理通过上调HO-1表达及增强其活性,减轻兔肺缺血再灌注损伤.
목적 평개혈홍소양합매-1(HO-1)재원격지체결혈예처리감경토폐결혈재관주손상중적작용.방법 일본대이백토24지,4～5월령,체중2.0～2.5 kg,채용수궤수자표법,장기분위4조(n=6):가수술조(S조)、결혈재관주조(I/R조)、원격지체결혈예처리조(RLIP조)화HO-1억제제자원계람+원격지체결혈예처리조(ZnPP+ RLIP조).채용결찰좌폐문60 min、재관주180 min적방법제비폐결혈재관주손상모형;결찰폐문전행후지결혈예처리:쌍후지결혈10 min,재관주10 min,중복3차;ZnPP+ RLIP조후지결혈예처리전10 min정맥주사자원계람10μrmol/kg.우재관주결속시,채집동맥혈양,진행혈기분석;취폐조직,광경하관찰병이학결과,진행폐손상평분(LIS평분);측정폐조직습/간중(W/D)비치、수과양화물매(MPO)활성、병이철(MDA)함량、HO-1표체급기활성.결과 여S조비교,I/R조PaO2강저,폐조직LIS평분、W/D비치、MPO활성、MDA함량、HO-1표체급기활성승고(P＜0.01);여I/R조비교,RLIP조PaO2、폐조직HO-1표체급기활성승고,폐조직LIS평분、W/D비치、MPO활성화MDA함량강저(P＜0.01);여RLIP조비교,ZnPP+ RLIP조PaO2、폐조직HO-1표체급기활성강저,폐조직LIS평분、W/D、MPO활성화MDA함량승고(P＜0.01).결론 원격지체결혈예처리통과상조HO-1표체급증강기활성,감경토폐결혈재관주손상.
Objective To evaluate the role of haeme oxygenase-1 (HO-1) in remote limb ischemic preconditioning (RLIP)-induced attenuation of lung ischemia-reperfusion (I/R) injury in rabbits.Methods Twenty-four Japanese White Rabbits,aged 4-5 months,weighing 2.0-2.5 kg,were randomly divided into 4 groups (n =6 each) using a random number table:sham operation group (S group),I/R group,RLIP group and zinc protoporphyrin (ZnPP,an inhibitor of HO-1) plus RLIP group (ZnPP + RLIP group).Lung I/R was produced by 60 min occlusion of the left lung hilum followed by 180 min of reperfusion in I/R,RLIP and ZnPP + RLIP groups.RLIP and ZnPP + RLIP groups received 3 cycles of 10 min ischemia followed by 10 min reperfusion in the bilateral hind limbs immediately before occlusion of the left lung hilum.In ZnPP + RLIP group,ZnPP 10 μmol/kg was injected intravenously 10 min prior to hind limb ischemia and the rest of the procedures were similar to those previously described in RLIP group.At the end of reperfusion,arterial blood samples were collected for blood gas analysis.The animals were then sacrificed and pulmonary specimens were obtained for microscopic examination of the pathological changes which were scored (lung injury score,LIS) and for determination of wet/dry lung weight ratio (W/D ratio),myleoperoxidase (MPO) activity,malondialdehyde (MDA) content and expression and activity of HO-1 in the lung tissues.Results Compared with group S,PaO2 was significantly decreased,and LIS,W/D ratio,MPO activity,MDA content,and HO-1 expression and activity were increased in I/R group (P ＜ 0.01).Compared with I/R group,PaO2 and HO-1 expression and activity were significantly increased,and LIS,W/D ratio,MPO activity and MDA content were decreased in RLIP group (P ＜ 0.01).Compared with RLIP group,PaO2 and HO-1 expression and activity were significantly decreased,and LIS,W/D ratio,MPO activity and MDA content were increased in ZnPP + RLIP group (P ＜ 0.01).Conclusion RLIP up-regulates HO-1 expression and enhances HO-1 activity,thus reducing lung I/R injury in rabbits.