Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
J Trauma Acute Care Surg. 2012 Nov;73(5):1138-44. doi: 10.1097/TA.0b013e318265d08d.
Mast cell activation plays a key role in the process of small intestinal ischemia-reperfusion (IIR) injury; however, the precise role of tryptase released from mast cell on IIR injury remains poorly understood. The aim of this study was to determine the protective role against IIR injury by using tryptase inhibitor protamine after ischemia and to explore the underlying mechanism.
Adult Sprague-Dawley rats were randomized into sham-operated group (S), sole IIR group (IIR) in which rats were subjected to 75-minute superior mesenteric artery occlusion followed by 4-hour reperfusion, or IIR being respectively treated with mast cell stabilizer cromolyn sodium (CS group), with the mast cell degranulator compound 48/80 (CP group), or with protamine (P group). The previously mentioned agents were, respectively, administered intravenously 5 minutes before reperfusion. The intestine tissue was obtained for histologic assessment and assays for protein expressions of tryptase and mast cell protease 7 and protease-activated receptor 2 (PAR-2). The intestine mast cell number and levels of tumor necrosis factor κ and interleukin 8 were quantified.
IIR resulted in intestinal injury evidenced as significant increases in Chiu's scores, accompanied with concomitant increases of mast cell counts and intestinal tryptase and mast cell protease 7 protein expressions. IIR also increased intestinal PAR-2 expressions, tumor necrosis factor κ, and interleukin 8 levels. Cromolyn sodium and protamine significantly reduced the responses to IIR injury while compound 48/80 further aggravated the previously mentioned biochemical changes.
Tryptase releasing from mast cell activation participates in IIR injury through PAR-2, and inhibiting tryptase after ischemia provides promising benefits in limiting IIR injury.
肥大细胞激活在小肠缺血再灌注（IIR）损伤过程中发挥关键作用；然而，肥大细胞释放的胰蛋白酶在 IIR 损伤中的确切作用仍知之甚少。本研究旨在通过在缺血后使用胰蛋白酶抑制剂鱼精蛋白来确定其对 IIR 损伤的保护作用，并探讨其潜在机制。
成年 Sprague-Dawley 大鼠随机分为假手术组（S）、单纯 IIR 组（IIR），其中大鼠接受肠系膜上动脉闭塞 75 分钟，然后再灌注 4 小时；或分别用肥大细胞稳定剂色甘酸钠（CS 组）、肥大细胞脱颗粒剂化合物 48/80（CP 组）或鱼精蛋白（P 组）处理 IIR。上述药物分别在再灌注前 5 分钟静脉注射。获取肠组织进行组织学评估和胰蛋白酶、肥大细胞蛋白酶 7 和蛋白酶激活受体 2（PAR-2）的蛋白表达检测。定量肠肥大细胞数量和肿瘤坏死因子 κ 和白细胞介素 8 的水平。
IIR 导致肠损伤，表现为 Chiu 评分显著升高，同时伴有肥大细胞计数和肠胰蛋白酶和肥大细胞蛋白酶 7 蛋白表达增加。IIR 还增加了肠 PAR-2 表达、肿瘤坏死因子 κ 和白细胞介素 8 水平。色甘酸钠和鱼精蛋白显著减轻了对 IIR 损伤的反应，而化合物 48/80 则进一步加重了上述生化变化。
肥大细胞激活释放的胰蛋白酶通过 PAR-2 参与 IIR 损伤，缺血后抑制胰蛋白酶可能对限制 IIR 损伤具有重要意义。
