Toll-like receptor 2 is protective of ischemia-reperfusion-mediated small-bowel injury in a murine model
Toll-like receptor 2 is protective of ischemia-reperfusion-mediated small-bowel injury in a murine model
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DOI：
10.1097/01.pcc.0000288717.44702.c0
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发表时间：
2008-01-01
影响因子：
4.1
通讯作者：
Dimmit, Reed A.
中科院分区：
文献类型：
--
作者：
Aprahamian, Charles J.;Lorenz, Robin G.;Dimmit, Reed A.
客观的。在小鼠肠道损伤模型中，我们假设 Toll 样受体 2 (TLR2)（一种共生细菌的识别分子）在粘膜免疫的发展中发挥重要作用，并通过调节先天性和获得性免疫来预防缺血/再灌注损伤。设计：介入性实验室研究。设置：学术医学研究中心。科目。四周大的 C57BL6 野生型 (n = 12) 和 C57BL6 TLR2 缺陷型小鼠 (TLR2(-/-)) (n = 12)。 干预措施：24 只小鼠仅接受剖腹手术或剖腹手术加肠系膜上动脉闭塞 (n 6/组) 60 分钟，然后恢复 90 分钟。 测量和主要结果：取空肠中部切片进行组织病理学和信使 RNA 表达（逆转录酶-聚合酶链反应，标准化为 18 秒和仅剖腹手术对照）。肠损伤评分从0（无损伤）到4（透壁坏死）。使用 Mann-Whitney U 检验和 Student's Mest 进行统计分析（p < .05 显着）。与野生型相比，TLR2(-/-) 小鼠在缺血/再灌注后肠道损伤评分升高（平均值+/- SEm）（2.17 +/- 0.40 与 0.67 +/- 0.33，p < .05）。干扰素-γ（0.29 +/- 0.12 vs. 3313 +/- 1710）、interieukin-4（0.25 +/- 0.13 vs. 2.70 +/- 1.08）和 interleukin-6（250.63 +/- 69.60 vs. 320,300）的肠道细胞因子信使 RNA（平均倍数变化 +/- SEM）与野生型相比，缺血/再灌注后 TLR2(-/-) 中的 +/- 215,964) 显着降低 (p < .05)。肿瘤坏死因子和信使RNA水平没有变化。结论：与野生型小鼠相比，TLR2(-/-)小鼠粘膜先天免疫反应失调，在缺血再灌注后无法产生保护性反应。这种肠道损伤的小鼠模型可能与早产儿的产后早期病程相关，早产儿可能因抗生素治疗而减少了 TLR2 表达和/或减少了腔内共生细菌，从而减少了 TLR2 介导的信号传导。
Objective. In a murine model of intestinal injury, we hypothesized that Toll-like receptor 2 (TLR2), a recognition molecule for commensal bacteria, plays an important role in the development of mucosal immunity and is protective against ischemia/reperfusion injury via the modulation of both innate and acquired immunity.Design: Interventional laboratory study.Setting: Academic medical research center. Subjects. Four-week-old C57BL6 wild-type (n = 12) and C57BL6 TLR2-deficient mice (TLR2(-/-)) (n = 12).Interventions: Twenty-four mice underwent laparotomy only or laparotomy plus superior mesenteric artery occlusion (n 6/group) for 60 mins, followed by 90 mins of recovery.Measurements and Main Results: Mid-jejunal sections were taken for histopathology and messenger RNA expression (reverse transcriptase-polymerase chain reaction, normalized to 18s and laparotomy-only controls). Intestinal injury was scored from 0 (no injury) to 4 (transmural necrosis). Statistical analyses were performed using Mann-Whitney U test and Student's Mest (p < .05 significant). TLR2(-/-) mice had elevated intestinal injury scores (mean +/- SEm) after ischemia/reperfusion vs. wild-type (2.17 +/- 0.40 vs. 0.67 +/- 0.33, p < .05). Intestinal cytokine messenger RNA (mean fold change +/- SEM) of interferon-gamma (0.29 +/- 0.12 vs. 3313 +/- 1710), interieukin-4 (0.25 +/- 0.13 vs. 2.70 +/- 1.08), and interleukin-6 (250.63 +/- 69.60 vs. 320,300 +/- 215,964) in TLR2(-/-) was significantly decreased (p < .05) after ischemia/reperfusion vs. wild-type. Tumor necrosis factor-et messenger RNA levels were unchanged.Conclusions: TLR2(-/-) mice have a dysregulated mucosal innate immune response and fail to mount a protective response after ischemia-reperfusion compared with wild-type mice. This murine model of intestinal injury may correlate with the early postnatal course of premature infants who may have decreased TLR2 expression and/or decreased luminal commensal bacteria secondary to antibiotic therapy, thus decreasing TLR2-mediated signaling.