Aprahamian Charles J, Lorenz Robin G, Harmon Carroll M, Dimmit Reed A
Department of Surgery, University of Alabama at Birmingham, USA.
Pediatr Crit Care Med. 2008 Jan;9(1):105-9. doi: 10.1097/01.PCC.0000288717.44702.C0.
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.
Interventional laboratory study.
Academic medical research center.
Four-week-old C57BL/6 wild-type (n = 12) and C57BL/6 TLR2-deficient mice (TLR2-/-) (n = 12).
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.
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 t-test (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), interleukin-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-alpha messenger RNA levels were unchanged.
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.
在肠道损伤的小鼠模型中，我们假设Toll样受体2（TLR2）作为共生菌的识别分子，在黏膜免疫的发展中起重要作用，并且通过调节先天免疫和获得性免疫来保护机体免受缺血/再灌注损伤。
干预性实验室研究。
学术医学研究中心。
4周龄的C57BL/6野生型小鼠（n = 12）和C57BL/6 TLR2基因缺陷小鼠（TLR2-/-）（n = 12）。
24只小鼠仅接受剖腹手术或剖腹手术加肠系膜上动脉阻断（n = 6/组）60分钟，随后恢复90分钟。
取空肠中段切片进行组织病理学检查和信使核糖核酸表达检测（逆转录-聚合酶链反应，以18s和仅接受剖腹手术的对照组为标准进行标准化）。肠道损伤从0分（无损伤）至4分（透壁坏死）进行评分。采用Mann-Whitney U检验和Student's t检验进行统计分析（p < .05为有显著性差异）。与野生型小鼠相比，TLR2-/-小鼠在缺血/再灌注后肠道损伤评分升高（平均值±标准误）（2.17±0.40对0.67±0.33，p < .05）。缺血/再灌注后，TLR2-/-小鼠肠道中干扰素-γ（0.29±0.12对3313±1710）、白细胞介素-4（0.25±0.13对2.70±1.08）和白细胞介素-6（250.63±69.60对320300±215964）的细胞因子信使核糖核酸水平显著降低（p < .05）。肿瘤坏死因子-α信使核糖核酸水平未发生变化。
与野生型小鼠相比，TLR2-/-小鼠黏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出生后的早期病程相关，早产儿可能因抗生素治疗导致TLR2表达降低和/或腔内共生菌减少，从而降低TLR2介导的信号传导。
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