Differential effect of imipenem treatment on wild-type and NK cell-deficient CD8 knockout mice during acute intra-abdominal injury
Differential effect of imipenem treatment on wild-type and NK cell-deficient CD8 knockout mice during acute intra-abdominal injury
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DOI：
10.1152/ajpregu.00678.2005
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发表时间：
2006-03-01
影响因子：
2.8
通讯作者：
Sherwood, ER
中科院分区：
文献类型：
--
作者：
Enoh, VT;Fairchild, CD;Sherwood, ER
Enoh, Victor T., Chad D. Fairchild, Cheng Y. Lin, Tushar K. Varma, Edward R. Sherwood。亚胺培南对野生型和NK细胞缺陷型CD8敲除小鼠急性腹内损伤的差异影响。[J] .中国生物医学工程学报，2016,31(2):387 - 398。2005年11月3日首次出版；doi: 10.1152 / ajpregu.00678.2005。-CD8敲除小鼠（CD8KO/ α AsGM1小鼠）通过抗asialogm1处理减少自然杀伤（NK）细胞，对盲肠结扎和穿刺（CLP）造成的损伤具有抗性。然而，clp引起的损伤是复杂的。潜在的损伤来源包括细菌传播、盲肠缺血和细菌毒素的易位。我们在CLP后用亚胺培南治疗野生型和CD8KO/ alpha AsGM1小鼠，以减少细菌传播。在不穿刺盲肠壁或结扎盲肠并去除盲肠内容物的情况下，对其他小鼠进行盲肠结扎。亚胺培南治疗使细菌数量减少了至少两个数量级。然而，所有野生型小鼠，无论是生理盐水还是亚胺培南，在CLP后42小时死亡，并表现出明显的低体温、代谢性酸中毒和高血浆细胞因子浓度。未穿刺盲肠结扎的野生型小鼠也死亡，尽管血液中细菌计数非常低，但盲肠结扎和盲肠内容物冲洗的野生型小鼠存活。在CD8KO/alpha AsGM1小鼠CLP中，亚胺培南治疗将存活率从50%提高到100%。CD8KO/ α AsGM1小鼠经盲肠结扎不穿刺后，长期生存率为80-90%。与野生型对照相比，CD8KO/alpha AsGM1小鼠的低温、代谢性酸中毒和细胞因子的产生都减弱了。这些结果表明，细菌传播不是CLP后野生型小鼠损伤的主要来源，但盲肠腔内肠道菌群的存在是盲肠损伤后诱导全身性炎症的必要条件。CD8KO/ α AsGM1小鼠对盲肠损伤的全身性表现具有抗性。
Enoh, Victor T., Chad D. Fairchild, Cheng Y. Lin, Tushar K. Varma, and Edward R. Sherwood. Differential effect of imipenem treatment on wild-type and NK cell-deficient CD8 knockout mice during acute intra-abdominal injury. Am J Physiol Regul Integr Comp Physiol 290: R685-R693, 2006. First published November 3, 2005; doi:10.1152/ajpregu.00678.2005.-CD8 knockout mice depleted of natural killer ( NK) cells by treatment with anti-asialoGM1 (CD8KO/ alpha AsGM1 mice) are resistant to injury caused by cecal ligation and puncture (CLP). However, CLP-induced injury is complex. Potential sources of injury include bacterial dissemination, cecal ischemia, and translocation of bacterial toxins. We treated wild-type and CD8KO/ alpha AsGM1 mice with imipenem after CLP to decrease bacterial dissemination. Additional mice were subjected to cecal ligation without puncture of the cecal wall or cecal ligation and removal of cecal contents. Imipenem treatment decreased bacterial counts by at least two orders of magnitude. However, all wild-type mice, whether treated with saline or imipenem, died by 42 h after CLP and exhibited significant hypothermia, metabolic acidosis, and high plasma cytokine concentrations. Wild-type mice subjected to cecal ligation without puncture also died, despite very low bacterial counts in blood, but wild-type mice subjected to cecal ligation and washout of cecal contents survived. In CD8KO/alpha AsGM1 mice subjected to CLP, imipenem treatment increased survival from 50% to 100%. After cecal ligation without puncture, long-term survival was 80-90% in CD8KO/alpha AsGM1 mice. Hypothermia, metabolic acidosis, and cytokine production were attenuated in CD8KO/alpha AsGM1 mice compared with wild-type controls. These results indicate that bacterial dissemination is not a major source of injury in wild-type mice after CLP, but the presence of gut flora in the cecal lumen is required for induction of systemic inflammation after cecal injury. CD8KO/alpha AsGM1 mice are resistant to the systemic manifestations of cecal injury.