Chen Gunng-Shinng, Huang Kuo-Feng, Huang Chien-Chu, Wang Jia-Yi
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan ; Division of Orthodontics & Dentofacial Orthopedics and Pedodontics, Department of Dentistry, Tri-Service General Hospital, Taipei 114, Taiwan.
Division of Neurosurgery, Department of Surgery, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 23142, Taiwan ; School of Medicine, Tzu Chi University, Hualien 97004, Taiwan.
Biomed Res Int. 2015;2015:729831. doi: 10.1155/2015/729831. Epub 2015 Feb 1.
Acute lung injury (ALI) occurs frequently in patients with severe traumatic brain injury (TBI) and is associated with a poor clinical outcome. Aquaporins (AQPs), particularly AQP1 and AQP4, maintain water balances between the epithelial and microvascular domains of the lung. Since pulmonary edema (PE) usually occurs in the TBI-induced ALI patients, we investigated the effects of a thaliporphine derivative, TM-1, on the expression of AQPs and histological outcomes in the lung following TBI in rats. TM-1 administered (10 mg/kg, intraperitoneal injection) at 3 or 4 h after TBI significantly reduced the elevated mRNA expression and protein levels of AQP1 and AQP4 and diminished the wet/dry weight ratio, which reflects PE, in the lung at 8 and 24 h after TBI. Postinjury TM-1 administration also improved histopathological changes at 8 and 24 h after TBI. PE was accompanied with tissue pathological changes because a positive correlation between the lung injury score and the wet/dry weight ratio in the same animal was observed. Postinjury administration of TM-1 improved ALI and reduced PE at 8 and 24 h following TBI. The pulmonary-protective effect of TM-1 may be attributed to, at least in part, downregulation of AQP1 and AQP4 expression after TBI.
急性肺损伤（ALI）在重度创伤性脑损伤（TBI）患者中频繁发生，且与不良临床预后相关。水通道蛋白（AQP），尤其是AQP1和AQP4，维持着肺上皮和微血管区域之间的水平衡。由于肺水肿（PE）通常发生在TBI诱导的ALI患者中，我们研究了一种噻吩卟啉衍生物TM-1对大鼠TBI后肺中AQP表达及组织学结果的影响。在TBI后3或4小时腹腔注射给予TM-1（10 mg/kg），可显著降低TBI后8小时和24小时肺中AQP1和AQP4升高的mRNA表达和蛋白水平，并降低反映PE的肺湿/干重比。损伤后给予TM-1还改善了TBI后8小时和24小时的组织病理学变化。PE伴有组织病理学改变，因为在同一动物中观察到肺损伤评分与湿/干重比之间呈正相关。损伤后给予TM-1可改善TBI后8小时和24小时的ALI并减轻PE。TM-1的肺保护作用可能至少部分归因于TBI后AQP1和AQP4表达的下调。
