中药复方HNA-1对地塞米松诱导小鼠胸腺萎缩的保护作用及对胸腺RLR信号通路的影响

Protective effect of HNA-1 on dexamethasone-induced thymus atrophy mice and its effect on RLR signal pathway

目的:探讨中药复方湘艾一号方(HNA-1)对地塞米松诱导的胸腺萎缩、胸腺输出功能的保护作用及胸腺RLR信号通路表达的影响。方法:将C57BL/6小鼠,随机分为正常对照组、模型组、HNA-1低、中、高剂量治疗组,左旋咪唑组。观察各组小鼠胸腺形态改变,检测外周血中T细胞受体重排删除环(TRECs)的含量、CD4+T初始亚群细胞的比例,并检测胸腺组织RLR/MAVS/IFN-α/β通路的表达情况。结果:模型组小鼠胸腺严重萎缩,组织结构破坏明显,外周血TRECs下降;RIG-Ⅰ、MDA5、LGP2和IFN-α/β表达上调明显。与模型组比较,HNA-1治疗组小鼠胸腺指数改变不显著,但胸腺细胞数量增加,以中、低剂量组较为明显;外周血TRECs含量升高,尤以低剂量组差异明显(P<0.05)。且HNA-1可明显抑制胸腺RLR信号通路的表达,以中剂量组最为明显(P<0.05)。结论:HNA-1对地塞米松诱导的胸腺萎缩小鼠具有一定的治疗作用,以中、低剂量较为明显,其机制可能与调控RLR通路的表达情况相关。

Objective:To investigate the effects of HNA-1,a traditional Chinese medicine regimen,on thymus output and RLR signaling pathway in thymic atrophy induced by dexamethasone in mice.Methods:C57 BL/6 mice were randomly divided into 6 groups,including normal control,model(intraperitoneal DEX injection)group,HNA-1 treated groups(administrated with HNA-1 in low,middle,and high doses),and Levamisole group.The changes of thymus morphology were measured,the routine pathology examinations were implemented,as well as the expressions of RLR/MAVS/IFN-α/β mRNA were detected.TRECs and the proportion of the naive CD4+T cell in peripheral blood were also detected.Results:Mic in model group showed a severe thymic atrophy with comprehensive structural damage.The levels of their TRECs in peripheral blood decreased.Simultaneously,their thymic expressions of RIG-Ⅰ,MDA5,LGP2,and IFN-α/β were significantly up-regulated.HNA-1 treatments in different doses could not obviously increase the thymus index,but they increased the number of thymocytes especially in the medium and low dose group observed.HNA-1 treatments increased the content of TRECs in peripheral blood,especially in low-dose group(P<0.05).Additionally,HNA-1 treatments significantly inhibited the upregulation of RIG-Ⅰ,MDA5,LGP2,IFN-α/βin thymus especially in the medium-dose group(P<0.05).Conclusion:HNA-1 has therapeutic effects on glucocorticoid-induced thymus atrophy in mice.The mechanisms are probably related to the activation of the RLR signaling pathway.