CAJ | 학술논문

目的探讨缺血预处理(IPC)后大鼠肺组织中缺血再灌注损伤(IRI)相关基因的表达,为研究IPC减轻IRI的分子机制提供依据.方法将雄性Wistar大鼠随机分为三组,缺血预处理组(IPC组,n:20)阻断左肺门5 min,开放10 min,如此重复3次,然后阻断左肺门,1 h后恢复血流灌注;缺血再灌注组(IR组,n=20)直接阻断左肺门,1 h后开放血流;假手术组(n=5)仅松解肺下部韧带,不做其它处理.IPC组和IR组分别于再灌注后1、3、6及24 h各取大鼠5只,切取左肺组织,采用含有22 226个大鼠基因点的Illumina RatRef-12全基因组表达谱微珠芯片检测肺组织中基因表达情况,比较IPC组与IR组各再灌注时间点基因表达的差异.结果与IR组再灌注1 h相比,IPC组再灌注1 h时有1849个基因表达发生改变,其中上调的有918个,下调的有931个.与IR组再灌注3 h相比,IPC组再灌注3 h时有2568个基因表达发生改变,其中上调的有1377个,下调的有1191个.与IR组再灌注6 h相比,IPC组再灌注6 h时有1370个基因表达发生改变,其中上调的有563个,下调的有807个.与IR组再灌注24 h相比,IPC组再灌注24 h时仅有77个基因表达发生改变,全部为下调.结论 IPC对缺血再灌注损伤肺组织中基因表达的影响主要在再灌注后6 h内,以3 h最为明显;IPC可能通过影响凋亡相关基因、氧化应激相关基因、炎症反应及循环相关基因、能量代谢相关基因的表达来减轻IRI.
목적 탐토결혈예처리(IPC)후대서폐조직중결혈재관주손상(IRI)상관기인적표체,위연구IPC감경IRI적분자궤제제공의거.방법 장웅성Wistar대서수궤분위삼조,결혈예처리조(IPC조,n:20)조단좌폐문5 min,개방10 min,여차중복3차,연후조단좌폐문,1 h후회복혈류관주;결혈재관주조(IR조,n=20)직접조단좌폐문,1 h후개방혈류;가수술조(n=5)부송해폐하부인대,불주기타처리.IPC조화IR조분별우재관주후1、3、6급24 h각취대서5지,절취좌폐조직,채용함유22 226개대서기인점적Illumina RatRef-12전기인조표체보미주심편검측폐조직중기인표체정황,비교IPC조여IR조각재관주시간점기인표체적차이.결과 여IR조재관주1 h상비,IPC조재관주1 h시유1849개기인표체발생개변,기중상조적유918개,하조적유931개.여IR조재관주3 h상비,IPC조재관주3 h시유2568개기인표체발생개변,기중상조적유1377개,하조적유1191개.여IR조재관주6 h상비,IPC조재관주6 h시유1370개기인표체발생개변,기중상조적유563개,하조적유807개.여IR조재관주24 h상비,IPC조재관주24 h시부유77개기인표체발생개변,전부위하조.결론 IPC대결혈재관주손상폐조직중기인표체적영향주요재재관주후6 h내,이3 h최위명현;IPC가능통과영향조망상관기인、양화응격상관기인、염증반응급순배상관기인、능량대사상관기인적표체래감경IRI.
Objective To supply the evidence of protective effect of ischemia preconditioning(IPC)on pulmonary ischemia reperfusion injury(IRI)from the perspective of molecular mechanism,the dynamic changes in gene expression profile in pulmonary tissues of rats were investigated.Methods Forty-five male Wistar rats were randomly divided into 3 groups:IPC group,IR group and control group.IPC group was subjected to IPC (5 min ischemia and 10 min reperfusion for 3 intermittent cycles)1 h before warm ischemia and respectively 1-h,3-h,6-h,and 24-h reperfusion(n=5 in each),IR group was interrupted with perfusion for 1 h followed by reperfusion for 1,3,6,and 24 h(n=5 in each),control group(n=5)received thoracotomy and ventilation for time-match without ischemia.An in situ ischemia-reperfusion lung injury rat model was established by occluding hilus of lung.The RatRef-12 Expression Beadchips of 22 226rat-specific genes were used to monitor global gene expression changes involved in all groups.Results As IPC group compared to IR group,there were 1849 genes varied at 1 h after reperfusion,including 918 up-regulated genes and 931 down-regulated genes;there were 2568 genes changed at 3 h after reperfusion,including 1377 up-regulated genes and 1191 down-regulated genes;there were 1370 genes expressed differently at 6 h after reperfusion,including 563 ulyregulated genes and 807 down-regulated genes;there were 77 genes altered at 24 h after reperfusion,which all were down-regulated.Conclusion The influence of IPC on the pulmonary gene expression was concentrated within 6 h after reperfusion,especially at 3 h.IPC had good effects on genes related to apoptosis,oxidative stress,inflammation,circulation,energy metabolism and so on,and thus IPC could attenuate the injury induced by ischemia reperfusion in rat lungs.