目的: 探讨低氧诱导因子-1α(Hypoxia inducible factor-1α,HIF-1α)的小干扰RNA(Small interfering, RNA,siRNA)对胶原诱导关节炎(Collagen induced arthritis,CIA)小鼠相关肺间质病变(Interstitial lung disease,ILD)的治疗效果及小鼠胸腺细胞中T淋巴细胞亚群的影响。方法: 建立类风湿关节炎的动物模型CIA小鼠,实验分为空白组、CIA模型组、阴性对照组和HIF-1α-siRNA组,空白组小鼠不做任何处理,阴性对照组小鼠尾静脉注射空载体腺病毒,HIF-1α-siRNA组小鼠尾静脉注射HIF-1α-siRNA腺病毒,每周1次,共4周。实验结束后麻醉断颈处死小鼠,流式细胞术检测小鼠胸腺中Th1和Th2、Th17和Treg比例的变化,HE染色观察小鼠肺组织的病理变化。结果: CIA模型组和阴性对照组小鼠胸腺细胞中Th1细胞和Th17细胞的比例升高,Th2细胞和Treg的比例下降,与空白组比较具有统计学意义(P＜0.05)。HIF-1α-siRNA组小鼠胸腺细胞中Th1和Th17细胞的比例降低,Th2细胞和Treg的比例升高,与CIA模型组和阴性对照组小鼠比较,有统计学意义(P＜0.05)。模型组小鼠肺组织中出现大量淋巴细胞浸润、肺泡壁被破坏,同时出现肺间质改变,HIF-1α-siRNA处理CIA小鼠后,小鼠肺组织淋巴细胞浸润情况、肺泡壁破坏程度及肺间质改变均有所减轻。结论: HIF-1α-siRNA可以降低胸腺细胞中Th1细胞和Th17细胞的比例,同时升高Th2细胞和Treg的比例,并减轻CIA小鼠肺组织的淋巴细胞浸润情况,缓减肺泡壁的破坏及肺间质的改变,提示HIF-1α-siRNA可以通过调控胸腺细胞中的T淋巴细胞亚群,对CIA小鼠引起的肺间质病变起治疗作用。

Objective: To investigate the effect of hypoxia inducible factor-1α(HIF-1 α)on collagen induced arthritis (CIA) mice with interstitial lung disease (ILD) and T lymphocyte subsets in thymocytes by small interfering RNA (siRNA) vector of HIF-1α. Methods: CIA mice were established and divided into control group, CIA model group, negative control group and HIF-1α-siRNA group. The mice in control group were not treated, and the mice in negative control group were injected with empty adenovirus and those of HIF-1α-siRNA group were injected with HIF-1α-siRNA adenovirus, once a week for 4 weeks. After the experiment, all thymus were collected and thymocytes were cultured, and the changes of Th1 cells and Th2 cells, Th17 cells and Tregs in thymus were detected by flow cytometry, the pathological changes of mice lung tissue were observed by HE staining. Results: the proportion of Th1 cells and Th17 cells in thymocytes of CIA model group and negative control group increased and the proportion of Th2 cells and Tregs decreased, which was statistically significant compared with control group (P＜0.05). The proportion of Th1 and Th17 cells in thymocytes of mice in HIF-1α-siRNA group decreased, while the proportion of Th2 cells and Treg increased. Compared with CIA model group and negative control group, the difference was statistically significant (P＜0.05); There were a lot of lymphocyte infiltration, alveolar wall destruction and lung interstitial changes in the lungs of mice in CIA model group. After HIF-1α-siRNA treated CIA mice, the lymphocyte infiltration in the lungs of mice, the destruction of alveolar wall and the changes of lung stroma were alleviated. Conclusion: HIF-1α-siRNA can reduce the ratio of Th1 cells to Th17 cells and increase the ratio of Th2 cells and Tregs in thymocytes, reduce the lymphocyte infiltration in the lung tissue of CIA mice, and slow down the destruction of alveolar wall and the change of lung stroma, suggesting that HIF-1α-siRNA can treat CIA mice with interstitial lung disease by regulating T cell subsets in thymocytes.