Department of Critical Care, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
Department of Nursing, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
Mol Med Rep. 2019 Oct;20(4):3347-3354. doi: 10.3892/mmr.2019.10561. Epub 2019 Aug 6.
Ulinastatin, a urinary trypsin inhibitor (UTI) is commonly used to treat patients with acute inflammatory disease. However, the underlying mechanisms of its anti‑inflammatory effect in acute lung injury (ALI) are not fully understood. The present study aimed to investigate the protective effect of UTI and explore its potential mechanisms by using a rat model of lipopolysaccharide (LPS)‑induced ALI. Rats were treated with 5 mg/kg LPS by intratracheal instillation. The histological changes in LPS‑induced ALI was evaluated using hematoxylin and eosin staining and the myeloperoxidase (MPO) activity was determined using ELISA. The wet/dry ratio (W/D ratio) of the lungs was used to assess the severity of pulmonary edema and Evans blue dye was used to evaluate the severity of lung vascular leakage. The results demonstrated that LPS administration induced histological changes and significantly increased the lung W/D ratio, MPO activity and Evans blue dye extravasation compared with the control group. However, treatment with UTI attenuated LPS‑induced ALI in rats by modifying histological changes and reducing the lung W/D ratio, MPO activity and Evans blue dye extravasation. In addition, LPS induced the secretion of numerous pro‑inflammatory cytokines in bronchoalveolar lavage fluid (BALF), including tumor necrosis factor‑α, interleukin (IL)‑6, IL‑1β and interferon‑γ; however, these cytokines were strongly reduced following treatment with UTI. In addition, UTI was able to reduce cellular counts in BALF, including neutrophils and leukocytes. Western blotting demonstrated that UTI significantly blocked the LPS‑stimulated MAPK and NF‑κB signaling pathways. The results of the present study indicated that UTI could exert an anti‑inflammatory effect on LPS‑induced ALI by inhibiting the MAPK and NF‑κB signaling pathways, which suggested that UTI may be considered as an effective drug in the treatment of ALI.
尿胰蛋白酶抑制剂（UTI）是一种常用于治疗急性炎症性疾病的药物。然而，其在急性肺损伤（ALI）中的抗炎作用的潜在机制尚不完全清楚。本研究旨在通过脂多糖（LPS）诱导的 ALI 大鼠模型来探讨 UTI 的保护作用及其潜在机制。通过气管内滴注的方式向大鼠给予 5mg/kg LPS。通过苏木精-伊红染色评估 LPS 诱导的 ALI 的组织学变化，通过 ELISA 测定髓过氧化物酶（MPO）活性。使用肺湿/干重（W/D 比值）评估肺水肿的严重程度，使用 Evans 蓝染料评估肺血管渗漏的严重程度。结果表明，与对照组相比，LPS 给药诱导组织学变化，并显著增加肺 W/D 比值、MPO 活性和 Evans 蓝染料渗出。然而，UTI 治疗可通过改变组织学变化和降低肺 W/D 比值、MPO 活性和 Evans 蓝染料渗出来减轻 LPS 诱导的 ALI。此外，LPS 诱导支气管肺泡灌洗液（BALF）中多种促炎细胞因子的分泌，包括肿瘤坏死因子-α、白细胞介素（IL）-6、IL-1β 和干扰素-γ；然而，这些细胞因子在 UTI 治疗后被强烈抑制。此外，UTI 还能够减少 BALF 中的细胞计数，包括中性粒细胞和白细胞。Western blot 分析表明，UTI 可显著阻断 LPS 刺激的 MAPK 和 NF-κB 信号通路。本研究结果表明，UTI 可通过抑制 MAPK 和 NF-κB 信号通路对 LPS 诱导的 ALI 发挥抗炎作用，这提示 UTI 可能被视为治疗 ALI 的有效药物。
