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胸腺肽α1对C57BL/6结节病肉芽肿模型小鼠的疗效分析

Effect of thymosin alpha 1 on C57BL/6 model mice with sarcoidosis granuloma

  • 摘要: 目的:探讨胸腺肽α1(Tα1)对结节病肉芽肿的作用。方法:将25只C57BL/6小鼠随机分为2组:模型组15只,空白对照组10只。模型组用分枝杆菌过氧化物歧化酶多肽A (superoxide dismutase A ,Sod A) 诱导结节病;空白对照组给予等剂量的磷酸盐缓冲液(PBS)。建模开始第22天,每组随机取5只小鼠处死。第22~35天,将模型组剩余的10只小鼠随机分为模型组和给药组,每组5只。给药组每天给予10 μg Tα1腹腔注射;模型组、空白对照组每天给予0.5 mL PBS腹腔注射。建模开始第36天,处死小鼠,评价肺、淋巴结的组织学改变;免疫组化法检测肉芽肿中CD4+T细胞和巨噬细胞的改变;流式细胞术检测外周血辅助性T细胞(Th1)、Th2、Th17、调节性T细胞(Treg)、CD4/CD8,并采用ELISA法检测血浆、肺组织匀浆中白细胞介素17A(IL-17A)、IL-10水平。 结果:模型组小鼠可见肉芽肿性变,肉芽肿中存在巨噬细胞和CD4+T细胞浸润;给药组组织病理学改善。给药组、模型组小鼠外周血Th1及Th17比例升高(P<0.05);各组外周血中Treg比例、Th2比例及CD4/CD8水平差异无统计学意义。模型组小鼠血浆IL-10水平降低(P<0.05);模型组小鼠血浆IL-17A水平升高(P<0.05)。3组小鼠肺组织IL-10含量差异无统计学意义;模型组小鼠肺组织IL-17A含量升高(P<0.05)。 结论:Tα1能减轻结节病肉芽肿小鼠病情,Tα1的治疗效应可能与降低结节病肉芽肿小鼠中较高水平的Th17相关,但结论尚须验证。

     

    Abstract: Objective:To investigate the effect of thymosin alpha 1 (Tα1) on the sarcoidosis granuloma. Methods:Twenty-five C57BL/6 mice were randomly divided into 2 groups: 15 in model group and 10 in blank control group. Mice in the model group were treated with superoxide dismutase A, whereas mice in the blank control group were treated with PBS of the same volume. Twenty-two days after the establishing of the model, 5 mice in each group were randomly selected and sacrificed. Twenty-two to 35 days after the establishing of the model, the remaining 10 mice in the model group were further randomly divided into two groups, 5 in the model group and 5 in the administration group, mice in the drug group was given an intraperitoneal injection of 10 μg Tα1 every day, and mice in the model group and the blank control group were given a intraperitoneal injection of 0.5 mL PBS every day. On the 36th day: mice were sacrificed, the histologic changes of the lung and lymph node were evaluated; CD4+T cells and macrophages in granuloma were detected by immunohistochemistry; the levels of Th1, Th2, Th17, Treg, and CD4/CD8 in peripheral blood were detected by flow cytometry; and the cytokines IL-17A and IL-10 in lung homogenate and plasma were analyzed by ELISA. Results:Mice in the model group showed granulomatous changes, and the macrophage specific antigen macrophage and CD4+T were positive in the granuloma. The histopathological changes improved in the administration group.The levels of Th1 and Th17 in peripheral blood of both treatment group and model group were higher than the control group (P<0.05). There was no significant difference in the levels of Treg, Th2, or CD4/CD8 ratio in peripheral blood among all groups. The plasma IL-10 level of the mice in the model group was lower than that in the control group (P<0.05); plasm IL-17A level of the mice in the model groups was higher than that in the control group (P<0.05). There was no significant difference in the lung-tissue IL-10 level among all groups; the lung-tissue IL-17A level of the mice in the model group was higher than that in the control group (P<0.05). 〖JP〗Conclusions:Tα1 has a therapeutic effect on sarcoidosis mice, which might be related to the downregulation of the Th17 level, while the results need to be approved.

     

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