Mast-Cell-Releasing Tryptase Triggers Acute Lung Injury Induced by Small Intestinal Ischemia-Reperfusion by Activating PAR-2 in Rats
Mast-Cell-Releasing Tryptase Triggers Acute Lung Injury Induced by Small Intestinal Ischemia-Reperfusion by Activating PAR-2 in Rats
复制标题
肥大细胞释放类胰蛋白酶通过激活 PAR-2 触发大鼠小肠缺血再灌注引起的急性肺损伤
DOI：
10.1007/s10753-011-9422-5
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发表时间：
2012-06-01
期刊：
影响因子：
5.1
通讯作者：
Hei, Ziqing
中科院分区：
文献类型：
--
作者：
Gan, Xiaoliang;Liu, Dezhao;Hei, Ziqing
肥大细胞已被证实参与小肠缺血再灌注（IIR）损伤，但肥大细胞释放的胰蛋白酶在IIR诱导的急性肺损伤（ALI）中的确切作用尚不清楚，我们的研究旨在观察胰蛋白酶在IIR引发的ALI中的作用及其潜在机制。将成年SD大鼠随机分为假手术组、单独IIR组（肠系膜上动脉阻断75 min再灌注4 h）和IIR组（分别用花色苷酸钠、鱼精蛋白和复方48/80治疗）。上述药物分别于再灌注前5分钟静脉给药。实验结束后取肺组织，检测胰蛋白酶、肥大细胞蛋白酶7 （MCP7）和蛋白酶活化受体2 （PAR-2）的蛋白表达。定量观察肺肥大细胞数量及IL-8水平。测量肺组织损伤评分和肺含水量。IIR导致肺损伤，表现为肺组织学评分和肺含水量显著升高，同时伴有胰蛋白酶和MCP7表达升高，肺中PAR-2表达和IL-8水平升高。用色胺酸钠稳定肥大细胞和用鱼精蛋白抑制胰蛋白酶可显著降低iir介导的ALI及上述生化变化，而用化合物48/80激活肥大细胞可进一步加重iir介导的ALI及上述参数的升高。肥大细胞释放的胰蛋白酶通过激活PAR-2产生IL-8介导肠缺血再灌注诱导的ALI。
Mast cell has been demonstrated to be involved in the small intestinal ischemia-reperfusion (IIR) injury, however, the precise role of tryptase released from mast cell on acute lung injury(ALI) induced by IIR remains to be elucidated, our study aimed to observe the roles of tryptase on ALI triggered by IIR and its underlying mechanism. Adult SD rats were randomized into sham-operated group, sole IIR group in which rats were subjected to 75 min superior mesenteric artery occlusion followed by 4 h reperfusion, or IIR being respectively treated with cromolyn sodium, protamine, and compound 48/80. The above agents were, respectively, administrated intravenously 5 min before reperfusion. At the end of experiment, lung tissue was obtained for assays for protein expressions of tryptase and mast cell protease 7 (MCP7) and protease-activated receptor 2 (PAR-2). Pulmonary mast cell number and levels of IL-8 were quantified. Lung histologic injury scores and lung water content were measured. IIR resulted in lung injury evidenced as significant increases in lung histological scores and lung water contents, accompanied with concomitant increases of expressions of tryptase and MCP7, and elevations in PAR-2 expressions and IL-8 levels in lungs. Stabilizing mast cell with cromolyn sodium and inhibiting tryptase with protamine significantly reduced IIR-mediated ALI and the above biochemical changes while activating mast cell with compound 48/80 further aggravated IIR-mediated ALI and the increases of above parameters. Tryptase released from mast cells mediates ALI induced by intestinal ischemia-reperfusion by activating PAR-2 to produce IL-8.