Zhang Wan-Fu, Zhu Xiong-Xiang, Hu Da-Hai, Xu Cheng-Feng, Wang Yun-Chuan, Lv Gen-Fa
Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
J Burn Care Res. 2011 May-Jun;32(3):e51-8. doi: 10.1097/BCR.0b013e318217f8ae.
Nonmetabolic effects of intensive insulin therapy in critically ill patients have been reported, but the underlying mechanisms are unclear. This study was designed to test the hypothesis that intensive insulin treatment would attenuate burn-induced acute lung injury by protecting the pulmonary microvascular endothelium. The rat model of burn injury was achieved by exposure to 92°C water for 18 seconds. The rats were randomly allocated into the sham, burn/normal saline (NS), and burn/intensive insulin treatment groups. Blood glucose level was maintained between 5 and 7 mmol/L in rats in the burn/intensive insulin treatment group. Pulmonary injury was assessed by hematoxylin and eosin staining, scanning electron microscopy, bronchoalveolar lavage fluid protein concentrations, the lung wet:dry weight ratio, and lung myeloperoxidase activity. Pulmonary microvascular endothelial cells were examined by transmission electron microscopy. Western blotting was used to determine the protein expression of caspase-3. Intensive insulin treatment markedly attenuated the acute lung injury, revealed by improvements in histological features and significant decreases in bronchoalveolar lavage fluid protein concentrations, pulmonary wet:dry weight ratio, and myeloperoxidase activity at 12 hours after injury (P < .05 or P < .01 vs burn/NS). Moreover, the injured pulmonary microvascular endothelial cells showed significant improvements, whereas caspase-3 was markedly downregulated in the burn/intensive insulin treatment group when compared with the burn/NS group. Overall, intensive insulin treatment efficiently attenuated pulmonary microvascular endothelial cell dysfunction, decreased cell apoptosis, and inhibited acute lung injury after a burn. These findings may be useful in preventing organ failure after burn injury.
已有报道称强化胰岛素治疗对重症患者有非代谢性影响，但其潜在机制尚不清楚。本研究旨在验证强化胰岛素治疗可通过保护肺微血管内皮来减轻烧伤诱导的急性肺损伤这一假说。通过将大鼠暴露于92°C水中18秒建立烧伤损伤模型。将大鼠随机分为假手术组、烧伤/生理盐水组和烧伤/强化胰岛素治疗组。烧伤/强化胰岛素治疗组大鼠的血糖水平维持在5至7 mmol/L之间。通过苏木精-伊红染色、扫描电子显微镜、支气管肺泡灌洗液蛋白浓度、肺湿重与干重之比以及肺髓过氧化物酶活性来评估肺损伤。通过透射电子显微镜检查肺微血管内皮细胞。采用蛋白质印迹法测定半胱天冬酶-3的蛋白表达。强化胰岛素治疗显著减轻了急性肺损伤，表现为组织学特征改善，且损伤后12小时支气管肺泡灌洗液蛋白浓度、肺湿重与干重之比及髓过氧化物酶活性显著降低（与烧伤/生理盐水组相比，P <.05或P <.01）。此外，与烧伤/生理盐水组相比，烧伤/强化胰岛素治疗组受损的肺微血管内皮细胞有显著改善，而半胱天冬酶-3明显下调。总体而言，强化胰岛素治疗有效减轻了烧伤后肺微血管内皮细胞功能障碍，减少了细胞凋亡，并抑制了急性肺损伤。这些发现可能有助于预防烧伤后器官功能衰竭。
