Effect of Recombinant Human Thrombomodulin on Ventilator-Induced Lung Injury in Septic Rats

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K20385
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Emergency medicine
• Research Institution: Mie University
• Principal Investigator: Iwashita Yoshiaki 三重大学, 医学系研究科, リサーチアソシエイト (90525396)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 人工呼吸関連肺障害 / 敗血症 / リコンビナントトロンボモジュリン

Outline of Final Research Achievements

High tidal ventilation with inflammation causes ventilator-induced lung injury (VILI). This study aimed to investigate the preventive effect of rTM on VILI in sepsis caused by HV ventilation. A total of 46 adult male rats were subcutaneously administered either 3mg/kg of rTM or saline. Twelve hours later, the rats were underwent cecal ligation and puncture (CLP). At 2 h after this procedure, the rats were placed on a ventilator set at either low tidal volume [(LV) 6 ml/kg] or high tidal volume (HV 35 ml/kg) ventilation for another 2 h. After 2 h of mechanical ventilation, the PaO2 was significantly lower and BALF protein was significantly higher in HV rats than in LV rats. The rTM did not improve oxygenation or BALF protein levels. Also in HV rats, lung tissue IL6 and MCP-1 mRNA levels were significantly higher in the rTM-treated rats. rTM does not improve oxygenation in a non-DIC, CLP-pretreated, high-tidal-ventilation rat model.

Free Research Field

集中治療

Academic Significance and Societal Importance of the Research Achievements

近年、rTMのDICのみならず、炎症性疾患に対する適応を拡大する動きがみられるが、今回の敗血症に人工呼吸関連肺障害を来し、DICは来していないモデルラットに対しては効果が確認できなかった。また、一部の分子学的マーカーでは、肺障害を悪化させる可能性が示唆された。
本研究はこれまでのrTMの有用性に関する研究結果を覆すものではないが、適応を十分に守ったうえで使用しないと病態を悪化させる可能性があることを示したという意味で意義があると考える。