Luo Hong-Min, Hu Sen, Zhou Guo-yong, Bai Hui-Ying, Lv Yi, Wang Hai-Bin, Lin Hong-Yuan, Sheng Zhi-Yong
Laboratory of Shock and Organ Dysfunction, Burns Institute, The First Hospital Affiliated to the People's Liberation Army General Hospital, 51 Fu Cheng Road, Beijing 100048, China.
Department of Clinical Laboratory, The First Hospital Affiliated to the People's Liberation Army General Hospital, 51 Fu Cheng Road, Beijing 100048, China.
Burns. 2013 Aug;39(5):916-22. doi: 10.1016/j.burns.2012.11.004. Epub 2012 Dec 5.
The aim of this study was to examine whether administration of ulinastatin inhibits pro-inflammatory mediators and ameliorate visceral vasopermeability both in a rat model of major burn, and also in rat cultured endothelial cells stimulated with permeability-evoking mediators.
Plasma levels of tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), myeloperoxidase (MPO), microvascular permeability, and water content of organ tissues were evaluated in a rodent model of a 55% TBSA full-thickness scald injury. Microvascular permeability was also evaluated with a cultured pulmonary microvascular endothelial cells (PMECs) monolayer after stimulation with trypsin, bradykinin, histamine, prostaglandin E2 and burn serum.
We found that the plasma levels of TNF-α, CRP, MPO, vascular permeability and water content of heart, lung, kidney, and small intestine tissues were significantly increased in animals after scald injury, and administration of ulinastatin lowered the levels TNF-α, CRP, MPO, vascular permeability and water content of those organ tissues. In vitro, ulinastatin lowered the levels of TNF-α, interleukin-6 (IL-6) and attenuated permeability in PMEC monolayers after being stimulated with burn serum or trypsin, but not by bradykinin, histamine or prostaglandin E2.
These results indicate that ulinastatin attenuates the systemic inflammatory response and visceral vasopermeability both in vivo and vitro, and may serve as a therapeutic agent for prevention of systemic inflammatory response and leakage of fluid into tissue after major burn.
本研究旨在探讨乌司他丁在大面积烧伤大鼠模型以及用通透性诱导介质刺激的大鼠培养内皮细胞中，是否能抑制促炎介质并改善内脏血管通透性。
在55%体表面积全层烫伤的啮齿动物模型中，评估肿瘤坏死因子-α（TNF-α）、C反应蛋白（CRP）、髓过氧化物酶（MPO）的血浆水平、微血管通透性以及器官组织的含水量。在用胰蛋白酶、缓激肽、组胺、前列腺素E2和烧伤血清刺激后，也用培养的肺微血管内皮细胞（PMECs）单层评估微血管通透性。
我们发现，烫伤后动物体内TNF-α、CRP、MPO的血浆水平、血管通透性以及心脏、肺、肾和小肠组织的含水量显著升高，而给予乌司他丁可降低这些器官组织的TNF-α、CRP、MPO、血管通透性和含水量。在体外，乌司他丁在用烧伤血清或胰蛋白酶刺激后，可降低PMEC单层中TNF-α、白细胞介素-6（IL-6）的水平并减轻通透性，但对缓激肽、组胺或前列腺素E2刺激无此作用。
这些结果表明，乌司他丁在体内和体外均可减轻全身炎症反应和内脏血管通透性，可能作为预防大面积烧伤后全身炎症反应和液体渗漏到组织中的治疗药物。
