Regenerative Medicine Department, Operational and Undersea Medicine Directorate, Naval Medical Research Center, Silver Spring, MD 20910, USA.
J Inflamm (Lond). 2012 Sep 25;9(1):34. doi: 10.1186/1476-9255-9-34.
Hemorrhagic shock results in systemic activation of the immune system and leads to ischemia-reperfusion injury. Lymphocytes have been identified as critical mediators of the early innate immune response to ischemia-reperfusion injury, and immunomodulation of lymphocytes may prevent secondary immunologic injury in surgical and trauma patients.
Yorkshire swine were anesthetized and underwent a grade III liver injury with uncontrolled hemorrhage to induce hemorrhagic shock. Experimental groups were treated with a lymphocyte depletional agent, porcine polyclonal anti-thymocyte globulin (PATG) (n = 8) and compared to a vehicle control group (n = 9). Animals were observed over a 3 day survival period. Circulating lymphocytes were examined with FACS analysis for CD3/CD4/CD8, and central lymphocytes with mesenteric lymph node and spleen staining for CD3. Circulating and lung tissue16 infiltrating neutrophils were measured. Circulating CD3 lymphocytes in the blood and in central lymphoid organs (spleen/lymph node) were stained and evaluated using FACS analysis. Immune-related gene expression from liver tissue was quantified using RT-PCR.
The overall survival was 22% (2/9) in the control and 75% (6/8) in the PATG groups, p = 0.09; during the reperfusion period (following hemorrhage) survival was 25% (2/8) in the control and 100% (6/6) in the PATG groups, p = 0.008. Mean blood loss and hemodynamic profiles were not significantly different between the experimental and control groups. Circulating CD3+CD4+ lymphocytes were significantly depleted in the PATG group compared to control. Lymphocyte depletion in the setting of hemorrhagic shock also significantly decreased circulating and lung tissue infiltrating neutrophils, and decreased expression of liver ischemia gene expression.
Lymphocyte manipulation with a depletional (PATG) strategy improves reperfusion survival in experimental hemorrhagic shock using a porcine liver injury model. This proof of principle study paves the way for further development of immunomodulation approaches to ameliorate secondary immune injury following hemorrhagic shock.
失血性休克会导致全身免疫系统激活，并导致缺血再灌注损伤。淋巴细胞已被确定为缺血再灌注损伤早期固有免疫反应的关键介质，淋巴细胞的免疫调节可能防止手术和创伤患者的二次免疫损伤。
用猪多克隆抗胸腺球蛋白（PATG）对麻醉后的约克夏猪进行 III 级肝损伤伴不受控制的出血以诱导失血性休克。实验组用淋巴细胞耗竭剂治疗（n=8），并与载体对照组（n=9）进行比较。动物在 3 天的存活期内进行观察。用 FACS 分析检测循环淋巴细胞的 CD3/CD4/CD8，用肠系膜淋巴结和脾脏染色检测中央淋巴细胞的 CD3。测量循环和肺组织 16 浸润中性粒细胞。用 FACS 分析对血液和中央淋巴器官（脾/淋巴结）中的循环 CD3 淋巴细胞进行染色和评估。用 RT-PCR 定量肝组织中的免疫相关基因表达。
对照组的总体存活率为 22%（2/9），PATG 组为 75%（6/8），p=0.09；在再灌注期（出血后），对照组的存活率为 25%（2/8），PATG 组为 100%（6/6），p=0.008。实验组和对照组之间的平均失血量和血流动力学特征没有显著差异。与对照组相比，PATG 组循环 CD3+CD4+淋巴细胞明显耗竭。失血性休克时的淋巴细胞耗竭也显著减少了循环和肺组织浸润的中性粒细胞，并降低了肝缺血基因表达。
用耗竭（PATG）策略对淋巴细胞进行操作，可改善猪肝脏损伤模型中实验性失血性休克再灌注的存活率。这项原理验证研究为进一步开发免疫调节方法以减轻失血性休克后的二次免疫损伤铺平了道路。
Zotero 插件
