脓毒症小鼠不同组织炎症因子及T细胞亚群动态变化

孙旗; 丁纯蕾; 范倩; 潘之得; 谭晶; 钱义明; 赵雷; 钱风华

doi:10.12025/j.issn.1008-6358.2022.20221114

脓毒症小鼠不同组织炎症因子及T细胞亚群动态变化

Dynamic changes of inflammatory factors and T cell subsets in different tissues in septic mice

摘要

摘要:
目的探讨通过盲肠结扎穿孔术（CLP）建立的脓毒症小鼠在疾病发展过程中，不同脏器炎症浸润程度以及免疫状态的变化特点。
方法对40只小鼠进行CLP建立脓毒症模型（CLP组），在术后0 h、6 h、12 h、24 h、48 h及72 h检测小鼠血液、肺组织及回肠组织中IL-6、IL-10、IL-2、IL-4的含量变化，并用流式细胞技术检测小鼠脾脏中Treg及Th17、回肠黏膜固有层中CD4⁺T及CD8⁺T淋巴细胞比例变化。另选择40只小鼠进行假手术，作为对照（假手术组）。
结果 CLP组小鼠肺组织及回肠组织中IL-6含量于术后6 h达峰值，血浆中IL-6含量于术后12 h达峰值，均高于同时间点假手术组小鼠（P < 0.01）。CLP组小鼠回肠组织中IL-10含量于术后6 h达峰值，高于假手术组（P < 0.01）；IL-2含量于术后持续上升，在术后24 h达峰值，高于假手术组（P < 0.01）。CLP组小鼠术后6 h及24 h的脾脏淋巴细胞中Th17、Treg比例明显高于同时间点假手术组（P < 0.01）；回肠黏膜固有层中CD4⁺T细胞比例于术后12 h达峰值，CD8⁺T细胞比例于术后24 h达峰值，均高于同时间点假手术组（P < 0.01）。脾脏淋巴细胞中Th17、Treg及回肠黏膜固有层中CD4⁺T及CD8⁺T细胞均于术后24 h下降。
结论脓毒症发病过程中，不同部位的炎症因子浸润程度不同，肠道黏膜中炎症反应出现较早且持续时间较长；脓毒症中后期CD8⁺T细胞减少、Treg比例相对较高，提示淋巴细胞增殖能力下降。

Abstract:
Objective To investigate the changes of inflammatory infiltration degree and immune status of different tissues in sepsis mice established by cecal ligation and perforation (CLP) during the development of the disease.
Methods 40 mice were used to establish sepsis model by CLP. The levels of IL-6, IL-10, IL-2 and IL-4 in blood, lung and ileum tissues were detected at 0 h, 6 h, 12 h, 24 h, 48 h and 72 h after operation. The percentages of Treg and Th17 in spleen and the proportions of CD4⁺T and CD8⁺T lymphocytes in lamina propria of ileum mucosa were detected by flow cytometry. 40 mice underwent sham operation were as the control.
Results The IL-6 level in lung and ileum reached the peak at 6 h after operation, and the IL-6 level in plasma reached the peak at 12 h after CLP, which was significantly higher than that in the sham group at the same time point (P < 0.01). The IL-10 level in ileum reached the peak at 6 h after CLP, which was significantly higher than that in sham group (P < 0.01). The level of IL-2 in ileum tissue increased continuously after CLP, and reached the peak at 24 h, which was significantly higher than that in sham group (P < 0.01). The percentages of Th17 and Treg in spleen at 6 h and 24 h after CLP were significantly higher than those in sham group at the same time point (P < 0.01); the CD4⁺T cell percentage in lamina propria of ileum mucosa reached the highest at 12 h after CLP, and CD8⁺T cell percentage reached the highest at 24 h after CLP, which were significantly higher than those in sham group (P < 0.01). The percentages of Th17, Treg in spleen, and CD4⁺T and CD8⁺T cells in lamina propria of ileum mucosa all decreased at 24 h after operation in the two groups.
Conclusions The infiltration degrees of inflammatory factors are different in different tissues during sepsis, and the inflammatory reaction in intestinal mucosa appears earlier and last longer; during the middle and late stage of sepsis, CD8⁺T cells decreasing and the Treg ratio relativly increasing imply that lymphocyte proliferation is decreased.

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