Depletion of intestinal resident macrophages prevents ischaemia reperfusion injury in gut
Depletion of intestinal resident macrophages prevents ischaemia reperfusion injury in gut
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DOI：
10.1136/gut.2003.034868
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发表时间：
2004-12-01
期刊：
影响因子：
24.5
通讯作者：
Tam, PKH
中科院分区：
文献类型：
--
作者：
Chen, Y;Lui, VCH;Tam, PKH
背景和目的：缺血再灌注（IR）损伤所涉及的细胞和分子事件很复杂，尚未完全了解。以往的研究表明，多形核中性粒细胞（PMN）是IR损伤的主要炎症细胞。然而，抗PMN抗血清治疗仅提供有限的保护，表明其他炎症细胞参与。因此，我们研究了居民巨噬细胞在IR损伤的贡献，IR肠injure.Methods模型：DA大鼠分为假手术组和IR组。将上级肠系膜动脉夹闭30、45或60分钟（缺血），然后再灌注60分钟。组织学染色评价IR损伤。早期生长反应因子1（Egr-1），髓过氧化物酶（MPO）和促炎细胞因子的表达进行了分析，免疫组化，逆转录-聚合酶链反应，和蛋白质印迹分析。结果：在45/60 min和60/60 min的IR肠段可见粘膜脱落和绒毛破坏，肠段内巨噬细胞数量明显减少，肠段内巨噬细胞数量明显减少，肠段内巨噬细胞数量明显减少。在45/60分钟和60/60分钟的IR肠中，在受损的粘膜区域未检测到PMN浸润。在60/60分钟的IR肠中，PMN定位于隐窝基部的毛细血管周围。再灌注3 h后，仅在受损绒毛中观察到明显的PMN浸润。升高的核Egr-1免疫染色定位于受损绒毛的巨噬细胞中，在粘膜损伤的组织学外观之前。此外，受损部位的驻留巨噬细胞表达MPO。促炎细胞因子RANTES和MCP-1的蛋白水平在IR肠中增加。居民巨噬细胞消耗二氯亚甲基二膦酸盐显着降低IR后大鼠肠粘膜损伤。结论：我们的研究结果表明，居民巨噬细胞发挥作用，在IR肠损伤的早期粘膜损伤。因此，巨噬细胞应作为IR损伤治疗干预的主要靶点。
Background and aims: The cellular and molecular events involved in ischaemia reperfusion (IR) injury are complex and not fully understood. Previous studies have implicated polymorphonuclear neutrophils (PMN) as major inflammatory cells in IR injury. However, anti-PMN antiserum treatment offers only limited protection, indicating that other inflammatory cells are involved. We have therefore investigated the contribution of resident macrophages in IR injury using an IR gut injury model.Methods: DA rats were divided into sham operation and IR groups. The superior mesenteric artery was clamped for 30, 45, or 60 minutes ( ischaemia) followed by 60 minutes of reperfusion. IR injuries were evaluated by histological staining. Expression of early growth response factor 1 (Egr-1), myeloperoxidase (MPO), and proinflammatory cytokines was analysed by immunohistochemistry, reverse transcription-polymerase chain reaction, and western blotting analysis. The specific role of macrophages in IR gut injury was also evaluated in resident macrophage depleted rats.Results: Mucosal sloughing and villi destruction were seen in 45/60 minute and 60/60 minute IR guts. PMN infiltration at the damaged mucosal area was undetectable in 45/60 minute and 60/60 minute IR guts. PMN were localised around the capillaries at the base of the crypts in 60/60 minute IR gut. Obvious PMN infiltration was only observed in damaged villi after three hours of reperfusion. Elevated nuclear Egr-1 immunostaining was localised in resident macrophages at the damaged villi before histological appearance of mucosal damage. Furthermore, resident macrophages at the damaged site expressed MPO. Protein levels of the proinflammatory cytokines RANTES and MCP-1 were increased in IR gut. Depletion of resident macrophages by dichloromethylene bisphosphonate significantly reduced mucosal damage in rat guts after IR.Conclusion: Our findings indicate that resident macrophages play a role in early mucosal damage in IR gut injury. Therefore, macrophages should be treated as a prime target for therapeutic intervention for IR damage.