Xu Y X, Wichmann M W, Ayala A, Cioffi W G, Chaudry I H
Department of surgery, Brown University School of Medicine, Providence, Rhode Island, USA.
J Surg Res. 1997 Feb 15;68(1):24-30. doi: 10.1006/jsre.1997.5006.
Although the thymus is an important organ in the ontogeny of T lymphocytes, little is known about the effects of hemorrhage and/or trauma on this organ. The objective of this study was to determine whether trauma-hemorrhage induces increased thymic apoptosis and, if so, which mediators may be involved. Male C3H/HeN mice underwent either sham operation, hemorrhagic shock (mean artery blood pressure of 35 +/- 5 mmHg for 90 min, followed by blood and fluid resuscitation), fracture of the right tibia, or fracture plus hemorrhage, respectively. At 3 days after the procedure, total viable thymocyte yield, thymocyte apoptosis (flow cytometry), thymus-derived IL-3 (bioassay), and GM-CSF (ELISA) were determined. The results demonstrate that fracture alone induces no significant change in the parameters measured. However, (i) there was a significant decrease in total viable thymocyte yield and an increase in thymocyte apoptosis following hemorrhage or fracture plus hemorrhage; (ii) thymocyte IL-3 release was significantly reduced after hemorrhage as well as fracture plus hemorrhage; (iii) thymus-derived GM-CSF was significantly increased after fracture plus hemorrhage, but not with hemorrhage alone. In conclusion, severe hemorrhage alone or coupled with fracture can induce thymus atrophy via apoptosis. In addition, the decreased IL-3 release suggests that apoptotic thymic involution may be due to the lack of growth factor support. Such dyshomeostasis may contribute to inappropriate/inadequate T cell maturation leading to host immune suppression following trauma-hemorrhage. Increased thymus-derived GM-CSF might be in part responsible for the systemic inflammatory response following trauma-hemorrhage.
虽然胸腺是T淋巴细胞个体发育过程中的一个重要器官，但关于出血和/或创伤对该器官的影响却知之甚少。本研究的目的是确定创伤性出血是否会诱导胸腺细胞凋亡增加，如果是，哪些介质可能参与其中。雄性C3H/HeN小鼠分别接受假手术、失血性休克（平均动脉血压为35±5 mmHg，持续90分钟，随后进行血液和液体复苏）、右胫骨骨折或骨折加出血处理。在手术后3天，测定总存活胸腺细胞产量、胸腺细胞凋亡（流式细胞术）、胸腺来源的IL-3（生物测定法）和GM-CSF（酶联免疫吸附测定法）。结果表明，单纯骨折不会引起所测参数的显著变化。然而，（i）出血或骨折加出血后，总存活胸腺细胞产量显著下降，胸腺细胞凋亡增加；（ii）出血以及骨折加出血后，胸腺细胞IL-3释放显著减少；（iii）骨折加出血后胸腺来源的GM-CSF显著增加，但单纯出血则无此现象。总之，单纯严重出血或合并骨折可通过凋亡诱导胸腺萎缩。此外，IL-3释放减少表明凋亡性胸腺退化可能是由于缺乏生长因子支持。这种内环境失调可能导致T细胞成熟异常/不足，从而导致创伤性出血后宿主免疫抑制。胸腺来源的GM-CSF增加可能部分导致了创伤性出血后的全身炎症反应。
