多西环素对EAE大鼠Th1/Th2细胞平衡及相关细胞因子的影响

Effect of doxycycline on Th1/Th2 cell balance and related cytokines in experimental allergic encephalomyelitis rats

目的探讨多西环素对实验性变态反应性脑脊髓炎(EAE)大鼠模型Th1/Th2细胞平衡的影响。方法将40只雌性Wistar大鼠分为EAE对照组及低、中、高剂量多西环素组,每组10只。观察大鼠发病情况及发病高峰期外周血单个核细胞(PBMC)分泌白细胞介素(IL)-4、干扰素-γ(IFN-γ)水平,测定高峰期脑组织IL-1β、IL-10、肿瘤坏死因子α(TNF-α)水平及脑脊液和血清清蛋白水平,计算脑脊液与血清清蛋白比值(QA值)。结果各剂量多西环素组大鼠临床症状较EAE对照组均减轻。各剂量多西环素组大鼠发病高峰期外周血单个核细胞(PBMC)分泌IFN-γ水平和IFN-γ/IL-4比值均较EAE对照组降低,分泌IL-4水平均较EAE对照组升高(P<0.01);高剂量多西环素组IL-4水平较中剂量多西环素组增高差异无统计学意义(P>0.05),其余各剂量多西环素组间差异有统计学意义(P<0.01)。各剂量多西环素组大鼠发病高峰期脑组织IL-1β、TNF-α水平及QA值较EAE对照组降低,IL-10水平较EAE对照组升高(P<0.05)。随多西环素剂量增加,各剂量多西环素组IL-1β、TNF-α水平及QA值越低,IL-10水平越高,且各组间差异有统计学意义(P<0.05)。结论多西环素可明显减轻EAE大鼠临床症状,其机制可能与多西环素降低大鼠Th1细胞因子水平,升高Th2细胞因子水平,纠正Th1/Th2细胞平衡,从而保护血脑屏障有关。

Objective To investigate the effect of doxyeycline on the Thl/Th2 cell balance in experimental allergic eneephalomyelitis（EAE） rats. Methods Forty female Wistar rats were randomly divided into the EAE control group,low,medium and high does DOX treatment groups, 10 cases in each group. The onset situation in rats was observed. The IL-4 and IFN-γ levels secreted by peripheral blood mononuclear cells （PBMC） at the peak stage were detected. The levels of IL-1β,IL-10,TNF-α in brain tissue,and the albumin content in cerebrospinal fluid and serum were detected. The QA value was calculated. Results In each DOX group,the clinical symptoms of rats were alleviated compared with the EAE control group. In each DOX group, the PBMC secreting IFN-γ level and IFN-γ/IL-4 ratio in the onset peak stage were lower than those in the EAE control group,while the IL-4 level was higher than that in the EAE control group（P〈0.01）. Compared with the medium-dose DOX group,the increase of IL-4 level in the high- dose DO group was unapparent（P〈0.05）, but the difference between other DOX groups had statistical significance（P〈0.01）. The IL-1β and TNF-α levels of brain tissue and QA value during onset peak stage in various doses DOX groups were decreased compared with the EAE control group,while the IL-10 level was increased compared with the EAE control group（P〈0.05）. With the DOX close increasing, the levels of IL-10, TNF-α and QA value in various doses DOX groups became lower, the IL-10 level became higher, there was statistically significant difference among various doses DOX groups （P 〈0. 05 ）. Conelusion DOX can obviously alleviate the clinical symptoms of EAE rats,its mechanism may be related with that DOX could decrease the level of Thl cytokine and increase the level of Th2 cytokine,correct the Thl/Th2 cell balance,thus protect the blood brain barrier（BBB）.