Biliverdin protects the functional integrity of a transplanted syngeneic small bowel
Biliverdin protects the functional integrity of a transplanted syngeneic small bowel
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DOI：
10.1053/j.gastro.2004.05.059
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发表时间：
2004-08-01
期刊：
影响因子：
29.4
通讯作者：
Bach, FH
中科院分区：
文献类型：
--
作者：
Nakao, A;Otterbein, LE;Bach, FH
背景与目的：Herne加氧酶-1(HO-1)在许多疾病模型中具有抗炎作用。通过降解血红素，HO-1产生一氧化碳(CO)、铁和胆绿素。我们研究了胆绿素是否能保护大鼠同基因小肠移植(SITx)免受损伤，如果是，通过什么机制。方法：用器官浴法评估运动能力。用逆转录聚合酶链式反应和分光光度法检测炎性细胞因子和介质。空肠段中性粒细胞行髓过氧化物酶组织化学染色。免疫印迹法检测胆绿素还原酶和HO-1的表达。通透性表示为外翻肠囊中荧光葡聚糖对浆膜的清除。结果：Bilk Verdin可显著提高SITx后(6h)受体的存活率。胆绿素治疗(1)可显著降低移植肠组织中一氧化氮合酶、环氧合酶-2、细胞间黏附分子-1以及炎性细胞因子IL-6、IL-1β的表达；(2)减少中性粒细胞在空肠肌层的浸润；(3)阻止SITx诱导的肠环肌收缩抑制。结论：胆绿素通过抗炎作用减轻移植后小肠损伤。重要的是，胆绿素提高了受体的存活率。将胆绿素发挥这些有益作用的机制与我们先前展示的吸入CO的机制进行了比较，表明这两种化合物(胆绿素和CO)部分地通过不同的机制发挥作用。这表明HO-1对血红素作用的不同产物可能起到相加或协同的保护作用。
Background & Aims: Herne oxygenase-1 (HO-1) protects against inflammation in many disease models. By degrading heme, HO-1 generates carbon monoxide (CO), iron and biliverdin. We investigated whether biliverdin would protect rat syngeneic small intestinal transplants (SITx) against damage and, if so, by what mechanism.Methods: Motility was assessed by organ bath techniques. Inflammatory cytokines and mediators were assessed by RT-PCR and spectrophotometric assays. Myeloperoxidase histochemistry for neutrophils was performed in jejunal segments. Western blots were performed for biliverdin reductase and HO-1 expression. Permeability was expressed as the mucosal to serosal clearance of fluorescent dextran in everted gut sacs. NF-kappaB activation was assessed via EMSA.Results: Bilk verdin significantly improved survival of recipients following SITx after prolonged intestinal ischemia (6 hours). Biliverdin treatment (1) led to a significant decrease in mRNA expression of NOS, Cox-2, and ICAM-1 as well as the inflammatory cytokines IL-6 and IL-1beta; (2) decreased neutrophil infiltration into the jejunal muscularis; and (3) prevented SITx-induced suppression of intestinal circular muscle contractility.Conclusions: Biliverdin administration attenuates transplantation-induced injuries to the small bowel by its anti-inflammatory action. Importantly, biliverdin enhanced recipient survival. A comparison of the mechanisms by which biliverdin exerted these salutary effects compared with inhalation of CO, which we previously showed had salutary effects, suggests that the 2 compounds (biliverdin and CO) exert their effects in part by different mechanisms. This implies that the different products of HO-1 action on heme may exert protective effects that are additive or synergistic.