Department of General, Visceral, Thoracic, and Vascular Surgery, University of Bonn, Bonn, Germany.
J Surg Res. 2012 Dec;178(2):866-73. doi: 10.1016/j.jss.2012.07.064. Epub 2012 Aug 15.
Heme oxygenase (HO-1) protects against inflammation. In this study, we investigated the protective function of hemin-induced HO-1 against lipopolysaccharide (LPS)-induced ileus.
Rats received LPS intraperitoneally 24 h after intraperitoneal hemin pretreatment or placebo. We also injected zinc protoporphyrin (ZnPP, 3rd group), an inhibitor of HO-1, intraperitoneally 2 h before LPS administration. To assess intestinal muscle function, we examined muscularis strip contractility in an organ bath and measured gastrointestinal transit in vivo. We investigated inflammation within the muscularis using polymerase chain reaction (interleukin [IL]-6, inducible nitric oxide synthase (iNOS), HO-1 and IL-10) 6 and 24 h after LPS.
Hemin significantly improved in vitro intestinal muscularis contractility (P < 0.001). In addition, hemin prevented LPS-induced dysmotility in vivo (gastrointestinal transit, geometric center: 8.39 ± 0.33 versus 5.68 ± 0.44; P < 0.001). In Zinc protoporphyrin (ZnPP)-treated animals, both parameters were significantly decreased compared with the hemin group. Messenger RNA expression demonstrated a significant reduction in IL-6 (6 h, hemin: 127.6 ± 36.7 versus LPS: 14,431 ± 5407; 24 h: 1.58 ± 0.39 versus 11.15 ± 2.59; P < 0.01) and iNOS (6 h: 2516 ± 985 versus 50,771 ± 13,321; 24 h: 55.11 ± 10.55 versus 257.1 ± 43.18; P < 0.001) in hemin-treated animals. Anti-inflammatory HO-1 messenger RNA levels (6 h, hemin: 116.3 ± 18.55 versus LPS: 26.02 ± 3.64; 24 h: 18.46 ± 2.69 versus 2.80 ± 0.32; P < 0.001) were increased. There was no significant difference in IL-10 levels at 6 and 24 h. ZnPP reversed the anti-inflammatory hemin effects.
Hemin induction of HO-1 diminishes LPS-induced sepsis. Heme oxygenase-1 has a central role in preventing sepsis-induced ileus. This benefit is reversed by HO-1 inhibition with ZnPP.
血红素加氧酶（HO-1）可抵抗炎症。在这项研究中，我们研究了血红素诱导的 HO-1 对脂多糖（LPS）诱导的肠梗阻的保护作用。
大鼠在腹腔内给予血红素预处理 24 小时后接受 LPS 腹腔内注射或安慰剂。我们还在 LPS 给药前 2 小时腹膜内注射锌原卟啉（ZnPP，第 3 组），一种 HO-1 抑制剂。为了评估肠肌功能，我们在器官浴中检查了肌层条带的收缩性，并在体内测量了胃肠道转运。我们在 LPS 后 6 和 24 小时使用聚合酶链反应（白细胞介素 [IL]-6、诱导型一氧化氮合酶（iNOS）、HO-1 和 IL-10）检测肌层内的炎症。
血红素显着改善了体外肠肌收缩力（P <0.001）。此外，血红素预防了 LPS 诱导的体内动力障碍（胃肠道转运，几何中心：8.39 ± 0.33 与 5.68 ± 0.44；P <0.001）。在 ZnPP 处理的动物中，与血红素组相比，这两个参数均显着降低。信使 RNA 表达显示白细胞介素 6（6 小时，血红素：127.6 ± 36.7 与 LPS：14,431 ± 5407；24 小时：1.58 ± 0.39 与 11.15 ± 2.59；P <0.01）和 iNOS（6 小时：2516 ± 985 与 50,771 ± 13,321；24 小时：55.11 ± 10.55 与 257.1 ± 43.18；P <0.001）的表达显着降低。血红素处理动物中抗炎性 HO-1 信使 RNA 水平（6 小时，血红素：116.3 ± 18.55 与 LPS：26.02 ± 3.64；24 小时：18.46 ± 2.69 与 2.80 ± 0.32；P <0.001）增加。在 6 小时和 24 小时时，IL-10 水平没有显着差异。ZnPP 逆转了血红素的抗炎作用。
血红素诱导的 HO-1 可减轻 LPS 诱导的败血症。血红素加氧酶-1 在预防败血症诱导的肠梗阻中起核心作用。这种益处被 ZnPP 抑制 HO-1 所逆转。
