Pan Yu, Fang Haizong, Lu Fengchun, Pan Minggui, Chen Fei, Xiong Ping, Yao Yi, Huang Heguang
General Surgery Department, Fujian Medical University Union Hospital, No.29 Xinquan Road, Fuzhou, 350001 People's Republic of China.
Department of Oncology and Hematology, Kaiser Permanente Medical Center, 710 Lawrence Expressway, Santa Clara, CA 95051 USA.
J Inflamm (Lond). 2017 Mar 20;14:7. doi: 10.1186/s12950-017-0154-7. eCollection 2017.
Ulinastatin or urinary trypsin inhibitor (UTI) has been shown to ameliorate the inflammatory response induced by experimental severe acute pancreatitis (SAP) and hence reduce the mortality, however the mechanism of its action remains incompletely understood. We have investigated the effect of ulinastatin on regulatory T-cells (Tregs) in an established rat model of SAP.
We established a rat SAP model by injecting 5% Na-taurocholate into the pancreatic duct and treated the SAP rats with ulinastatin with different dose level (5000, 10000, 30000 U/kg) through intraperitoneal injection at 0, 6 and 12 h.
We showed that the tissue damage of pancreas and the mortality of the SAP rats were significantly reduced by ulinastatin. We also showed that in the SAP rats the frequencies of CD4 T cells and Tregs, as well as the expressions of TGF-β1, CTLA-4, and Foxp3 were decreased in the SAP animals while IL-1β, IL-10 and TNF-α were significantly increased. Treatment with ulinastatin up-regulated the proportion of Tregs in CD4 T cells and the expression of IL-10, Foxp3 and CTLA-4 in the SAP rats in a dose dependence fashion, while down-regulating the levels of L-1β and TNF-α, myeloperoxidase (MPO) activity.
Our findings suggest that ulinastatin alleviates inflammatory response and tissue damage in SAP rats by increasing the proportion of Tregs. Our study provides a new mechanism for the beneficial effect of ulinastatin in SAP rat model.
乌司他丁或尿胰蛋白酶抑制剂（UTI）已被证明可改善实验性重症急性胰腺炎（SAP）诱导的炎症反应，从而降低死亡率，但其作用机制仍未完全明确。我们在已建立的大鼠SAP模型中研究了乌司他丁对调节性T细胞（Tregs）的影响。
通过向胰管注射5%牛磺胆酸钠建立大鼠SAP模型，并在0、6和12小时通过腹腔注射不同剂量水平（5000、10000、30000 U/kg）的乌司他丁对SAP大鼠进行治疗。
我们发现乌司他丁可显著降低胰腺的组织损伤和SAP大鼠的死亡率。我们还发现，在SAP大鼠中，CD4 T细胞和Tregs的频率以及TGF-β1、CTLA-4和Foxp3的表达均降低，而IL-1β、IL-10和TNF-α显著升高。乌司他丁治疗以剂量依赖方式上调了SAP大鼠CD4 T细胞中Tregs的比例以及IL-10、Foxp3和CTLA-4的表达，同时下调了L-1β和TNF-α的水平、髓过氧化物酶（MPO）活性。
我们的研究结果表明，乌司他丁通过增加Tregs的比例减轻了SAP大鼠的炎症反应和组织损伤。我们的研究为乌司他丁在SAP大鼠模型中的有益作用提供了一种新机制。
