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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。
Objective To investigate the role and significance of high mobility group clusterin 1 (HMGB1) in intestinal ischemia reperfusion injury (IRI) in rats. Methods Adult male Sprague-Dawley rats were randomly divided into 3 groups. Group A: sham operation group (n = 36), only open abdominal surgery, only the superior mesenteric artery was separated and not blocked. Group B: IRI group ), The superior mesenteric artery was occluded 60 minutes after reperfusion. Group C: IRI + HMGB1 antibody intervention group (n = 36). HMGB1 antibody was injected intraperitoneally at 200 μg / kg 1 h before operation. The same method was used to establish the small intestine IRI model in group B. The levels of HMGB1 in serum and small intestine were detected at 3, 6, 12, 24, 48, and 72 h after reperfusion respectively. Meanwhile, the degree of intestinal epithelial damage and the levels of serum IL-6 and TNF-α were measured. Results In normal rats, a small amount of HMGB1 was expressed. HMGB1 expression was significantly increased by IRI. After 3 h of reperfusion, HMGB1 expression began to increase, peaked at 12 h, decreased gradually at 24 h and 48 h, and gradually decreased to within 48 h Pre-blood levels. Serum IL-6 and TNF-α levels trends basically consistent with changes in HMGB1. At 3 h after reperfusion, the intestinal mucosa villous epithelial cells were completely detached and the height of villi was significantly reduced. At 6 h, some of the lamina propria disintegrated. On both sides of the intestinal mucosal villi, epithelial cells became lumpy at 12 h, and intestinal mucosa regenerated at 24 h. Intestinal mucosal membrane more obvious, further increase the height of villi; reperfusion 72h intestinal villi height was significantly increased, close to normal. After intervention with HMGB1 antibody, the degree of intestinal damage, IL-6 and TNF-α levels in serum were significantly lower than those in IRI group (P <0.05). Conclusions IRI can induce a significant increase of HMGB1 expression in rats, and HMGB1 is closely related to the degree of intestinal damage. This indicates that HMGB1 plays an important role in IRI of small intestine. Detection of HMGB1 may be used as an important index to predict and assess IRI in small intestine. Inhibition of HMGB1 expression may open up a new way of prevention and treatment of small intestine IRI.