Kao Raymond L C, Xu Xuemei, Xenocostas Anargyros, Parry Neil, Mele Tina, Martin Claudio M, Rui Tao
From the Department of National Defense, Royal Canadian Medical Services (R.L.C.K.), Ottawa; Critical Care Western, Department of Medicine (R.L.C.K., N.P., T.M., C.M.M., T.R.), Schulich School of Medicine and Dentistry, Division of Hematology (A.X.), Department of Medicine, Schulich School of Medicine and Dentistry, Western University; and Center for Critical Illness Research (R.L.C.K., C.M.M., T.R.), Lawson Health Research Institute, London, ON, Canada.
J Trauma Acute Care Surg. 2017 Aug;83(2):256-262. doi: 10.1097/TA.0000000000001539.
The study aims to evaluate whether C-peptide can reduce gut injury during hemorrhagic shock (HS) and resuscitation (R) therefore attenuate shock-induced inflammation and subsequent acute lung injury.
Twelve-week-old male mice (C57/BL6) were hemorrhaged (mean arterial blood pressure maintained at 35 mm Hg for 60 minutes) and then resuscitated with Ringer's lactate, followed by red blood cell transfusion with (HS/R) or without C-peptide (HS/R + C-peptide). Mouse gut permeability, bacterial translocation into the circulatory system and intestinal pathology, circulating HMGB1, and acute lung injury were assessed at different times after R. The mice in the control group underwent sham procedures without HS.
Compared to the sham group, the mice in the HS/R group showed increased gut permeability (6.07 ± 3.41 μg of FD4/mL) and bacterial translocation into the circulatory system (10.05 ± 4.92, lipopolysaccharide [LPS] of pg/mL), and increased gut damage; conversely, mice in the HS/R + C-peptide group showed significantly reduced gut permeability (1.59 ± 1.39 μg of FD4/mL; p < 0.05) and bacterial translocation (4.53 ± 1.08 pg of LPS/mL; p < 0.05) with reduced intestine damage. In addition, mice in the HS/R group had increased circulating HMGB1 (21.64 ± 14.17 ng/mL), lung myeloperoxidase) activity (34.4 ± 8.91 mU/g of tissue), and pulmonary protein leakage (2.33 ± 1.16 μg Evans blue/g tissue per minute). Mice in the HS/R + C-peptide group showed decreased HMGB1 (7.27 ± 1.93 ng/mL; p < 0.05), lung myeloperoxidase (23.73 ± 8.39 mU/g of tissue; p < 0.05), and pulmonary protein leakage (1.17 ± 0.42 Evans Blue/g tissue per minute; p < 0.05).
Our results indicate that C-peptide exerts beneficial effects to attenuate gut injury and dysfunction, therefore diminishing lung inflammation and subsequent injury in mice with HS and R.
本研究旨在评估C肽是否能减轻失血性休克（HS）及复苏（R）过程中的肠道损伤，从而减轻休克诱导的炎症反应及随后的急性肺损伤。
12周龄雄性小鼠（C57/BL6）进行出血（平均动脉血压维持在35 mmHg 60分钟），然后用乳酸林格氏液复苏，随后进行红细胞输注（HS/R）或输注C肽（HS/R + C肽）。在复苏后的不同时间评估小鼠肠道通透性、细菌易位至循环系统及肠道病理学、循环中的高迁移率族蛋白B1（HMGB1）以及急性肺损伤情况。对照组小鼠进行假手术，不进行HS。
与假手术组相比，HS/R组小鼠肠道通透性增加（FD4为6.07 ± 3.41 μg/mL），细菌易位至循环系统增加（脂多糖[LPS]为10.05 ± 4.92 pg/mL），肠道损伤加重；相反，HS/R + C肽组小鼠肠道通透性显著降低（FD4为1.59 ± 1.39 μg/mL；p < 0.05），细菌易位减少（LPS为4.53 ± 1.08 pg/mL；p < 0.05），肠道损伤减轻。此外，HS/R组小鼠循环中的HMGB1增加（21.64 ± 14.17 ng/mL），肺髓过氧化物酶活性增加（34.4 ± 8.91 mU/g组织），肺蛋白渗漏增加（2.33 ± 1.16 μg伊文思蓝/g组织每分钟）。HS/R + C肽组小鼠HMGB1降低（7.27 ± 1.93 ng/mL；p < 0.05），肺髓过氧化物酶降低（23.73 ± 8.39 mU/g组织；p < 0.05），肺蛋白渗漏降低（1.17 ± 0.42伊文思蓝/g组织每分钟；p < 0.05）。
我们的结果表明，C肽发挥有益作用，减轻肠道损伤和功能障碍，从而减轻HS和R小鼠的肺部炎症及随后的损伤。
