Inhibiting tryptase after ischemia limits small intestinal ischemia-reperfusion injury through protease-activated receptor 2 in rats
Inhibiting tryptase after ischemia limits small intestinal ischemia-reperfusion injury through protease-activated receptor 2 in rats
复制标题
缺血后抑制类胰蛋白酶通过蛋白酶激活受体 2 限制大鼠小肠缺血再灌注损伤
DOI：
10.1097/ta.0b013e318265d08d
复制
发表时间：
2012-11
期刊：
影响因子：
--
通讯作者：
Liu D*, Gan X*, Huang P, Chen X, Ge M, Hei Z
中科院分区：
文献类型：
--
作者：
Liu D*, Gan X*, Huang P, Chen X, Ge M, Hei Z
肥大细胞活化在小肠缺血再灌注（IIR）损伤过程中起关键作用；然而，肥大细胞释放的胰蛋白酶在IIR损伤中的确切作用仍然知之甚少。本研究旨在探讨胰蛋白酶抑制剂鱼精蛋白对缺血后IIR损伤的保护作用，并探讨其机制。方法将成年sd - dawley大鼠随机分为假手术组(S)、单独IIR组（IIR）， IIR组大鼠接受75 min肠系膜上动脉阻断后再灌注4 h， IIR组大鼠分别给予肥大细胞稳定剂色莫利钠（CS组）、肥大细胞脱颗粒剂48/80 （CP组）、鱼精蛋白（P组）治疗。上述药物分别于再灌注前5分钟静脉给予。取肠组织进行组织学评估，并检测胰蛋白酶、肥大细胞蛋白酶7和蛋白酶活化受体2 （PAR-2）的蛋白表达。肠肥大细胞数量与肿瘤坏死因子水平；白细胞介素8定量测定。结果IIR导致肠道损伤，Chiu’s评分显著升高，同时肥大细胞计数、肠胰酶和肥大细胞蛋白酶7蛋白表达升高。IIR还能提高肠道PAR-2表达、肿瘤坏死因子&kgr；和白细胞介素8水平。色胺酸钠和鱼精蛋白显著降低了IIR损伤的反应，而化合物48/80进一步加重了上述生化变化。结论肥大细胞活化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对限制IIR损伤有积极作用。
BACKGROUND 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. METHODS 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 &kgr; and interleukin 8 were quantified. RESULTS 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 &kgr;, 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. CONCLUSION 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.
登录
查看更多内容
影响因子：
4.8
作者：
S. Thakurdas;E. Melicoff;L. Sansores-García;Daniel C. Moreira;Youlia M. Petrova;R. Stevens;Roberto Adachi
通讯作者：
S. Thakurdas;E. Melicoff;L. Sansores-García;Daniel C. Moreira;Youlia M. Petrova;R. Stevens;Roberto Adachi
影响因子：
6.1
作者：
Z. Hei;Pin-jie Huang;Xiaoliang Gan;Hong-yu Pang;Jing Wei
通讯作者：
Z. Hei;Pin-jie Huang;Xiaoliang Gan;Hong-yu Pang;Jing Wei
影响因子：
2.8
作者：
Rattmann, Yanna D.;Pereira, Carlos R.;da Silva-Santos, J. Eduardo
通讯作者：
da Silva-Santos, J. Eduardo
影响因子：
20.3
作者：
Kemna, E;Pickkers, P;Swinkels, D
通讯作者：
Swinkels, D
影响因子：
3.5
作者：
Shea-Donohue T;Notari L;Stiltz J;Sun R;Madden KB;Urban JF Jr;Zhao A
通讯作者：
Zhao A