调节性T细胞在热射病大鼠发病机制中的作用探讨

赵佳佳; 张科学; 周京江; 胡婕; 宋青

doi:10.3969/j.issn.2095-5227.2021.06.011

调节性T细胞在热射病大鼠发病机制中的作用探讨

Role of regulatory T cells in pathogenesis of heat stroke in rats

摘要

摘要:
背景热射病(heat stroke，HS)具有高致死率的特点，导致其发生的相关炎性反应的细胞学机制尚未探明。
目的探讨大鼠发生热射病后血清及脾中CD4⁺CD25⁺ Foxp3⁺调节性T细胞(regulatory T cells，Tregs)及血清中相关因子的变化。
方法成年雄性SD大鼠60只随机分为Control组(n=10)和HS组(n=50)，建立HS大鼠模型。HS组按发病后6 h、12 h、24 h、48 h、72 h取样时间点分为5个亚组(n=10)。检测各亚组大鼠血清细胞因子肿瘤坏死因子α(tumor necrosis factor-α，TNF-α)、白细胞介素-2(interleukin-2，IL-2)、IL-6、转化生长因子β(transforming growth factor-β，TGF-β)、IL-10；流式细胞学技术检测各时间点亚组大鼠外周血、脾组织Tregs比例及脾组织Tregs凋亡率。
结果与Control组比较，HS组大鼠血清中细胞因子在各时间点均显著升高(P＜0.05)，其中促炎因子TNF-α、IL-2在12 h达高峰，IL-6在24 h达高峰，抗炎因子TGF-β、IL-10呈逐渐升高趋势。HS组血清中Tregs比例在6 h时低于Control组(P＜0.05)，之后呈升高趋势，在48 h、72 h时高于Control组(P均＜0.01)。HS组脾中Tregs比例在6 h及12 h时低于Control组(P均＜0.05)，之后呈升高趋势，在24 h、48 h、72 h时高于Control组。HS组在6 h时脾中Treg凋亡率较Control组升高，之后呈逐渐降低趋势，于24 h开始低于Control组(P＜0.05)。Pearson相关性分析显示，血清中IL-10、TGF-β变化与血及脾中的Tregs变化呈正相关，与脾组织中Tregs的凋亡率呈负相关。
结论 Tregs可能参与了HS的炎性反应发病机制。

Abstract:
Background Heat stroke is characterized by high mortality and the cytological mechanism of the inflammatory response has not been elucidated.
Objective To investigate the changes of Tregs and related factors in serum and spleen after heat stroke (HS) in rats.
Methods Sixty adult male SD rats were randomly divided into control group (n=10) and HS group (n=50). Then HS group was divided into 5 subgroups (n=10) according to the sampling time points of 6 h, 12 h, 24 h, 48 h and 72 h after onset. The HS rat model was established in HS group. The serum cytokines TNF-α, IL-2, IL-6, TGF-β and IL-10 were detected. The percentage of Tregs in peripheral blood, spleen and the apoptosis rate of Tregs in spleen were detected by flow cytometry.
Results Compared with the control group, the serum cytokine levels in the HS group increased significantly at each time point (P＜0.05). The pro-inflammatory factors TNF-α and IL-2 peaked at 12 h and IL-6 peaked at 24 h. The anti-inflammatory factors TGF-β and IL-10 showed a gradually increasing trend. The proportion of Tregs in the serum of HS group was lower than that of the control group at 6 h (P＜0.05), and then gradually increased, while it was higher than that of the control group at 48 h and 72 h (P＜0.01). The proportion of Tregs in the spleen of the HS group was lower than that of the control group at 6 h and 12 h (P＜0.05), and then gradually increased, which was higher than that of the control group at 24 h, 48 h and 72 h. At 6 h, the apoptosis rate of Treg in the spleen of the HS group was higher than that of the control group, and then gradually decreased, which was lower than that of the control group at 24 h (P＜0.05). Pearson correlation analysis showed that the changes in IL-10 and TGF-β in serum were positively correlated with the changes in Tregs of blood and spleen and negatively correlated with the apoptosis rate of Tregs in spleen tissue.
Conclusion Tregs are probably involved in the pathogenesis of HS by regulating the changes of inflammatory factors IL-10 and TGF-β.

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