匹多莫德辅助化疗对肺结核大鼠外周血T淋巴细胞亚群的影响及其机制探讨

Effect of pidotimod as an adjuvant chemotherapy on peripheral blood T lymphocyte subsets in rat models of pulmonary tuberculosis and its mechanisms

摘要:

目的 探究匹多莫德辅助化疗对肺结核大鼠外周血T淋巴细胞亚群的影响及其作用机制。方法 从65只大鼠中随机选取15只作为对照组，其余大鼠复制肺结核模型，随机分为模型组，化疗组及联合治疗组，每组15只。化疗组给予异烟肼50 mg/kg，利福霉素SV钠50 mg/kg，联合治疗组在化疗组基础上给予匹多莫德200 mg/kg，对照组、模型组给予等量生理盐水。连续治疗8周后，比较大鼠外周血CD3⁺、CD4⁺、CD8⁺，胸腺指数及血清IgG水平，肺组织Toll样受体4（TLR4）、核转录因子κB（NF-κB）、髓样细胞分化因子88（MyD88）蛋白表达。结果 与对照组比较，模型组、化疗组CD3⁺、CD4⁺，胸腺指数和IgG水平均降低（P <0.05），CD8⁺和TLR4、MyD88、NF-κB蛋白相对表达量均升高（P <0.05）；与模型组比较，化疗组及联合治疗组CD3⁺、CD4⁺、胸腺指数和IgG水平均升高（P <0.05），CD8⁺和TLR4、MyD88、NF-κB蛋白相对表达量均降低（P <0.05）；与化疗组比较，联合治疗组CD3⁺、CD4⁺、胸腺指数和IgG水平均升高（P <0.05），CD8⁺，TLR4、MyD88、NF-κB蛋白相对表达量均降低（P <0.05）。结论 匹多莫德辅助化疗能够提高肺结核大鼠免疫功能，其作用机制可能与TLR/NF-κB信号通路有关。

Abstract:

Objective To explore the effect of pidotimod as an adjuvant chemotherapy on peripheral blood T lymphocyte subsets in rat models of pulmonary tuberculosis (PTB) and its mechanisms.Methods Fifteen of the 65 rats were randomly selected as the control group, and the other rats were used to establish PTB models and randomly divided into model group, chemotherapy group and combined treatment group, with 15 rats in each group. The chemotherapy group was given 50 mg/kg of isoniazid and 50 mg/kg of rifamycin SV sodium, while the combined treatment group was additionally given 200 mg/kg of pidotimod. In contrast, the control group and the model group were given the same amount of normal saline. The frequency of CD3⁺, CD4⁺, and CD8⁺ cells in peripheral blood, the thymus index, serum levels of IgG, and the protein expressions of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and nuclear transcription factor κB (NF-κB) in the lung tissues of rats were compared.Results Compared with the control group, the frequency of CD3⁺ and CD4⁺ cells, the thymus index and the serum level of IgG were decreased in the model group and the chemotherapy group (P < 0.05), while the frequency of CD8⁺ cells and the relative protein expressions of TLR4, MyD88 and NF-κB were increased in the model group and the chemotherapy group (P < 0.05). Compared with the model group, the frequency of CD3⁺ and CD4⁺ cells, the thymus index and the serum level of IgG were increased in the chemotherapy group and the combined treatment group (P < 0.05), while the frequency of CD8⁺ cells and the relative protein expressions of TLR4, MyD88 and NF-κB were decreased in the chemotherapy group and the combined treatment group (P < 0.05). Compared with the chemotherapy group, the frequency of CD3⁺ and CD4⁺ cells, the thymus index and the serum level of IgG were increased in the combined treatment group (P < 0.05), while the frequency of CD8⁺ cells and the relative protein expressions of TLR4, MyD88 and NF-κB were decreased in the combined treatment group (P < 0.05).Conclusions Pidotimod as an adjuvant chemotherapy could improve the immune function of rats with PTB, the mechanism of which may be related to the TLR/NF-κB signaling pathway.