CpG-ODNs对慢性哮喘小鼠气道重塑的影响及机制

摘要

Objective To investigate the effect of CpG-oligodeoxynucleotides (CpG-ODNs) on airway remodeling in ovalbumin (OVA)-sensitized chronic asthmatic model in mice and the action mechanisms. Methods Forty female Balb/c mice were randomly divided into saline group, OVA group, OVA + CpG-ODNs group, and OVA+GpC-ODNs group, with 10 in each. At the end of OVA exposure, mice were evaluated for the development of airway remodeling. Blood and bronchoalveolar lavage fluid (BAD were collected for the measurement of OVA specific IgE, interleukin-4 (IL-4), interferon-γ (IFN-γ) , interleukin-10 (IL-10) and leukocytes count. Results Mice exposed to recurrent airway OVA challenge had chronic inflammation and airway remodeling, including inflammatory cell infiltration, subepithelial collagen deposition, goblet cell hyperplasia-meta-plasia and proliferation of airway smooth muscle cells. The eosinophil percentage and IL-4 in BAL, OVA specific IgE in serum in OVA group were all increased obviously compared with those in saline group (P<0. 01). CpG-ODNs could partially relieve the above changes in OVA group (P<0.05). Furthermore, mice treated with CpG-ODNs had slightly increased IFN-γ and IL-10 in BAL, suggesting that Thl and Treg cytokines might be responsible for the protective role of CpG-ODNs. However, GpC-ODNs did not affect OVA-induced pathological or immuno-logical changes (P>0.05). Conclusion Our results indicate that CpG-ODNs have therapeutic effects on chronic asthmatic airway remodeling by inducing immuno-resistance mediated by T cells and elevating Th1-to-Treg cytokines.%目的 探讨疫苗佐剂CpG-ODNs对慢性哮喘气道重塑的影响及机制.方法 采用卵蛋白(OVA)致敏并激发制备哮喘小鼠气道重塑动物模型,给予CpG-ODNs、GpC-ODNs干预,与生理盐水对照组、哮喘气道重塑模型组比较,观察其对哮喘气道重塑病理、肺泡灌洗液白细胞分类计数、细胞因子以及外周血免疫球蛋白的影响.结果 模型组小鼠可见气道壁炎症细胞浸润、上皮下胶原沉着、平滑肌增殖和杯状细胞增生等慢性哮喘气道重塑的病理改变,血清OVA特异性IgE上升明显(P＜0.01),支气管肺泡灌洗液(BALF)中嗜酸粒细胞及IL-4升高(P＜0.01),CpG-ODNs部分抑制了上述病理过程(P＜0.05),同时轻度升高IFN-γ及IL-10. GpC-ODNs对上述过程无明显影响.结论 CpG-ODNs能够通过上调Th1/Th2比例以及诱导调节性T细胞(Treg细胞)介导的免疫耐受,发挥对慢性哮喘气道重塑的防治作用.