Fan Wei, Nakazawa Koichi, Abe Shinya, Inoue Miori, Kitagawa Masanobu, Nagahara Noriyuki, Makita Koshi
Crit Care. 2013 Apr 28;17(2):R83. doi: 10.1186/cc12697.
Previous studies have shown that patients with diabetes mellitus appear to have a lower prevalence of acute lung injury. We assumed that insulin prescribed to patients with diabetes has an anti-inflammatory property and pulmonary administration of insulin might exert beneficial effects much more than intravenous administration.
Twenty-eight mechanically ventilated rabbits underwent lung injury by saline lavage, and then the animals were allocated into a normoglycemia group (NG), a hyperglycemia group (HG), an HG treated with intravenous insulin (HG-VI) group or an HG treated with aerosolized insulin (HG-AI) group with continuous infusion of different fluid solutions and treatments: normal saline, 50% glucose, 50% glucose with intravenous insulin, or 50% glucose with inhaled aerosolized insulin, respectively. After four hours of treatment, the lungs and heart were excised en bloc, and then high-mobility group B1 concentration in bronchoalveolar lavage fluid, interleukin-8 and toll-like receptor 4 mRNA expression in bronchoalveolar lavage fluid cells, and lung myeloperoxidase activity were measured.
Treatment with both aerosolized insulin and intravenous insulin attenuated toll-like receptor 4 mRNA expressions in the bronchoalveolar lavage fluid cells. Interleukin-8 and toll-like receptor 4 mRNA expression was significantly lower in the HG-AI group than in the HG-IV group. The lung myeloperoxidase activity in the normal healthy group showed significantly lower levels compared to the NG group but not different compared to those of the HG, HG-VI and HG-AI groups.
The results suggest that insulin attenuates inflammatory responses in the lungs augmented by hyperglycemia in acute lung injury and the insulin's efficacy may be better when administered by aerosol.
先前的研究表明，糖尿病患者急性肺损伤的患病率似乎较低。我们推测，给糖尿病患者开具的胰岛素具有抗炎特性，肺部给药胰岛素可能比静脉给药产生更多有益效果。
28只机械通气的兔子通过盐水灌洗造成肺损伤，然后将动物分为正常血糖组（NG）、高血糖组（HG）、静脉注射胰岛素治疗的高血糖组（HG-VI）或雾化吸入胰岛素治疗的高血糖组（HG-AI），分别持续输注不同的液体溶液并进行不同治疗：生理盐水、50%葡萄糖、含静脉注射胰岛素的50%葡萄糖或含吸入雾化胰岛素的50%葡萄糖。治疗4小时后，将肺和心脏整块切除，然后测定支气管肺泡灌洗液中高迁移率族蛋白B1浓度、支气管肺泡灌洗细胞中白细胞介素-8和Toll样受体4 mRNA表达以及肺髓过氧化物酶活性。
雾化吸入胰岛素和静脉注射胰岛素治疗均减弱了支气管肺泡灌洗细胞中Toll样受体4 mRNA表达。HG-AI组白细胞介素-8和Toll样受体4 mRNA表达显著低于HG-IV组。正常健康组的肺髓过氧化物酶活性与NG组相比显著降低，但与HG、HG-VI和HG-AI组相比无差异。
结果表明，胰岛素可减轻急性肺损伤中高血糖所致的肺部炎症反应，雾化给药时胰岛素的疗效可能更好。
