Mast cells activation contribute to small intestinal ischemia reperfusion induced acute lung injury in rats

Mast cells activation contribute to small intestinal ischemia reperfusion induced acute lung injury in rats
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肥大细胞激活导致大鼠小肠缺血再灌注诱导的急性肺损伤

DOI:
10.1016/j.injury.2011.12.027
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发表时间:
2012-08-01
影响因子:
2.5
通讯作者:
Hei, Ziqing
Hei, Ziqing
中科院分区:
医学3区
文献类型:
--
作者:
Huang, Pinjie;Liu, Dezhao;Hei, Ziqing

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背景:小肠缺血再灌注损伤可导致严重的局部和远端组织损伤,尤其是急性肺损伤(ALI)。肥大细胞活化在IIR损伤中起重要作用。方法:成年SD大鼠随机分为假手术组(S组)、单纯肠系膜上动脉阻断75min再灌注4h组(IIR组)、肥大细胞稳定剂克罗莫林钠组(IIR+CS组)、类胰蛋白酶拮抗剂鱼精蛋白(IIR+P组)、组胺受体拮抗剂酮替芬(IIR+K组)、肥大细胞脱颗粒剂复合48/80组(IIR+CP组)。分别于再灌流前5min静脉注射上述药物。实验结束后,取肺组织进行组织学观察及类胰蛋白酶和肥大细胞蛋白酶7(MCP7)蛋白表达的检测。结果:肺组织学评分明显增加(P<0.05),肺组织学评分明显增加(P<0.05),肥大细胞计数增加,血清中肿瘤坏死因子-α和IL-8浓度升高,组胺水平降低(均P<0.05与S比较)。IIR还增加了肺组织类胰蛋白酶和MCP7蛋白的表达(均P<0.05,IIR vs.S)。色甘酸钠、酮替芬和鱼精蛋白显著减少,而化合物48/80加重IIR所致的ALI及上述生化改变(P<0.05)。结论:肥大细胞活化在IIR所致的ALI中起重要作用。(C)2012爱思唯尔有限公司。保留所有权利。
Background: Small intestinal ischemia-reperfusion (IIR) injury may lead to severe local and remote tissue injury, especially acute lung injury (ALI). Mast cell activation plays an important role in IIR injury. It is unknown whether IIR mediates lung injury via mast cell activation.Methods: Adult SD rats were randomized into sham operated group (S), sole IIR group (IIR) in which rats were subjected to 75 min of superior mesenteric artery occlusion followed by 4 h reperfusion, or IIR being respectively treated with the mast cell stabilizer Cromolyn Sodium (IIR + CS group), with the tryptase antagonist Protamine (IIR + P group), with the histamine receptor antagonist Ketotifen (IIR + K group), or with the mast cell degranulator Compound 48/80 (IIR + CP group). The above agents were, respectively, administrated intravenously 5 min before reperfusion. At the end of experiment, lung tissue was obtained for histologic assessment and assays for protein expressions of tryptase and mast cell protease 7(MCP7). Pulmonary mast cell number and levels of histamine, TNF-alpha and IL-8 were quantified.Results: IIR resulted in lung injury evidenced as significant increases in lung histological scores (P < 0.05 IIR vs. S), accompanied with concomitant increases of mast cell counts and elevations in TNF-alpha and IL-8 concentrations and reductions in histamine levels (all P < 0.05 IIR vs. S). IIR also increased lung tissue tryptase and MCP7 protein expressions (all P < 0.05, IIR vs. S). Cromolyn Sodium, Ketotifen and Protamine significantly reduced whilst Compound 48/80 aggravated IIR mediated ALI and the above biochemical changes (P < 0.05).Conclusions: Mast cells activation play a critical role in IIR mediated ALI. (C) 2012 Elsevier Ltd. All rights reserved.