CAJ | 학술논문

目的：探讨高迁移率簇蛋白1（HMGB1）在大鼠小肠缺血再灌注损伤（IRI）中的作用及意义。方法选用成年雄性SD大鼠，随机分成3组，A组：假手术组（n＝36），仅行开关腹手术，只分离肠系膜上动脉，不阻断；B组：IRI组（n＝36），阻断肠系膜上动脉60 min后复灌；C组：IRI＋HMGB1抗体干预组（n＝36），术前1 h给予HMGB1抗体200μg/kg腹腔注射。与B组采用同样的方法建立小肠IRI模型。分别在复灌3、6、12、24、48、72 h后检测血清及小肠组织内HMGB1水平，同时测小肠上皮损伤程度、血清中IL-6及TNF-α水平。结果正常大鼠有少量HMGB1表达，IRI可致HMGB1表达水平显著增高，复灌3 h后HMGB1表达开始升高，12 h达峰值，24 h及48 h时逐渐下降，72 h内基本降至缺血前水平。血清中IL-6及TNF-α水平变化趋势基本与HMGB1变化一致。复灌3 h时肠黏膜绒毛上皮细胞完全脱落，绒毛高度明显降低；6 h时部分固有膜崩解；12 h时肠黏膜绒毛两边上皮细胞成块脱落；24 h出现肠黏膜再生；48 h时肠黏增生膜更加明显，绒毛高度进一步增加；再灌注72 h时肠黏膜绒毛高度明显增加、接近正常。给予HMGB1抗体干预治疗后，肠损伤程度、血清中IL-6及TNF-α较IRI组显著下降（P＜0.05）。结论大鼠小肠IRI能致大鼠HMGB1表达显著增高，HMGB1水平与肠损伤程度密切相关，这提示HMGB1在小肠 IRI 发挥了重要作用，检测 HMGB1水平可作为预测和评估小肠 IRI 程度的重要指标，通过抑制HMGB1表达可能为防治小肠IRI开辟新的防治途径。
목적：탐토고천이솔족단백1（HMGB1）재대서소장결혈재관주손상（IRI）중적작용급의의。방법선용성년웅성SD대서，수궤분성3조，A조：가수술조（n＝36），부행개관복수술，지분리장계막상동맥，불조단；B조：IRI조（n＝36），조단장계막상동맥60 min후복관；C조：IRI＋HMGB1항체간예조（n＝36），술전1 h급여HMGB1항체200μg/kg복강주사。여B조채용동양적방법건립소장IRI모형。분별재복관3、6、12、24、48、72 h후검측혈청급소장조직내HMGB1수평，동시측소장상피손상정도、혈청중IL-6급TNF-α수평。결과정상대서유소량HMGB1표체，IRI가치HMGB1표체수평현저증고，복관3 h후HMGB1표체개시승고，12 h체봉치，24 h급48 h시축점하강，72 h내기본강지결혈전수평。혈청중IL-6급TNF-α수평변화추세기본여HMGB1변화일치。복관3 h시장점막융모상피세포완전탈락，융모고도명현강저；6 h시부분고유막붕해；12 h시장점막융모량변상피세포성괴탈락；24 h출현장점막재생；48 h시장점증생막경가명현，융모고도진일보증가；재관주72 h시장점막융모고도명현증가、접근정상。급여HMGB1항체간예치료후，장손상정도、혈청중IL-6급TNF-α교IRI조현저하강（P＜0.05）。결론대서소장IRI능치대서HMGB1표체현저증고，HMGB1수평여장손상정도밀절상관，저제시HMGB1재소장 IRI 발휘료중요작용，검측 HMGB1수평가작위예측화평고소장 IRI 정도적중요지표，통과억제HMGB1표체가능위방치소장IRI개벽신적방치도경。
Objective To investigate the role and its significance of high mobility group box chromosomal protein 1(HMGB1) in ischemia-reperfusion injury in the rat small intestine. Methods Normal male Sprague-Dawley rats[(280±20)g] were randomly divided into sham-operated group (A group, n=36), intestinal ischemia-reperfusion injury group (B group, n=36), and ischemia-reperfusion injury control group (C group, n=36). A group was subjected to surgical manipulation without intestinal ischemia. B and C group were subjected to superior mesenteric artery occlusion for 60 minutes and reperfusion. In C group anti-HMGB1 antibody (200μg/kg) were also administered intraperitoneally one hour before operation. Detecting the level of HMGB1 expression in serum and intestinal tissue 3, 6, 12, 24, 48 and 72 hours after reperfusion, and the damage degree of intestinal epithelium and the serum concentrations of TNF-αand IL-6 should also be measured. Results A small amount of HMGB1 could be expressed in normal mice, while it increased markedly in the mice treated with intestinal ischemia-reperfusion injury. HMGB1 concentrations increased 3h after reperfusion, peaked at 12h and then decreased. 72 h after reperfusion it almost returned to the level before ischemia. The variation trend of serum IL-6 and TNF-α level was approximately the same as HMGB1. After 3 h of reperfusion intestinal mucosal villus epithelial cells fell off completely, and the villi height was decreased obviously. After 6 h part of Lamina propria disrupted. At the 12 h intestinal villus epithelial cells on both sides shed into pieces. 24 h after reperfusion intestinal mucosa started to regenerate and be more obvious in the next 24 h. The villi height increased to nearly normal levels after 72 h. The expression of HMGB1, TNF-αand IL-6, and the small intestinal epithelium damage degree were significantly higher in B group than in C group (P<0.05). Conclusions HMGB1 in intestinal ischemia-reperfusion increases markedly and the level of HMGB1 is directly bound up with intestinal injury degree, indicating that it plays a major role in intestinal ischemia-reperfusion injury. We suggest that HMGB1 level can be an important index in the prediction and evaluation of intestinal ischemia-reperfusion injury degree, and by inhibiting HMGB1expression we could open a new avenue for preventing intestinal ischemia-reperfusion injury.