Equine Clinic, Freie Universitaet Berlin, Germany.
Animal Medicine Department, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt.
Mediators Inflamm. 2019 Jun 17;2019:7845623. doi: 10.1155/2019/7845623. eCollection 2019.
Inhalation of immunostimulatory bacterial DNA segments (cytosine-phosphate-guanosine-oligodeoxynucleotides, CpG-ODN) normalizes clinical and cytologic parameters in severe equine asthma. We hypothesized that CpG-ODN inhalation also reduces the misbalance of elastinolytic activity in asthmatic horses.
Twenty asthmatic horses diagnosed by clinical examinations using a scoring system were included. All horses inhaled CpG-ODNs for 14 days in 2-day intervals. Matrix metalloproteinase (MMP-2/-9) and tissue inhibitors of metalloproteinase (TIMP-1/-2) concentrations were measured in tracheal aspirates using equine sandwich ELISAs before and 2 and 6 weeks after CpG-ODN inhalation.
MMP and TIMP concentrations correlated with the results of clinical scoring in all stages of equine asthma. Inhalation therapy led to significant reductions in clinical scores. MMP-2, MMP-9, and TIMP-2 concentrations were significantly reduced immediately, and all MMP and TIMP concentrations 6 weeks after therapy.
In equine asthma, overexpression of MMPs contributes to pathological tissue destruction, while TIMPs counteract MMPs with overexpression leading to fibrosis formation. The results of this study show that CpG-ODN inhalation may be an effective therapy to address a misbalance in equine asthma.
Misbalance of elastinolytic activity seems to improve by CpG-ODN inhalation for at least 6 weeks posttherapy, which may reduce the remodeling of the extracellular matrix. Further studies should evaluate this effect in comparison to glucocorticoid inhalation therapy.
CpG-ODN inhalation may be an effective therapy in the prevention of pulmonary fibrosis formation in equine asthma.
吸入免疫刺激性细菌 DNA 片段（胞嘧啶-磷酸-鸟嘌呤-寡脱氧核苷酸，CpG-ODN）可使严重马气喘病的临床和细胞学参数正常化。我们假设 CpG-ODN 吸入还可以减少气喘马中弹性蛋白水解活性的失衡。
纳入 20 例经临床评分系统诊断为气喘的马。所有马匹每隔 2 天吸入 CpG-ODN 14 天。在 CpG-ODN 吸入前、后 2 周和 6 周，使用马夹心 ELISA 测量气管抽吸物中的基质金属蛋白酶（MMP-2/-9）和金属蛋白酶组织抑制剂（TIMP-1/-2）浓度。
MMP 和 TIMP 浓度与马气喘的所有阶段的临床评分结果相关。吸入治疗导致临床评分显著降低。MMP-2、MMP-9 和 TIMP-2 浓度立即显著降低，治疗后 6 周所有 MMP 和 TIMP 浓度均降低。
在马气喘中，MMPs 的过度表达导致病理性组织破坏，而 TIMPs 则通过过度表达来对抗 MMPs 导致纤维化形成。本研究结果表明，CpG-ODN 吸入可能是一种有效的治疗方法，可以解决马气喘中的失衡问题。
CpG-ODN 吸入至少在治疗后 6 周内似乎可以改善弹性蛋白水解活性的失衡，这可能会减少细胞外基质的重塑。进一步的研究应评估与糖皮质激素吸入治疗相比，这种效果如何。
CpG-ODN 吸入可能是预防马气喘中肺纤维化形成的有效治疗方法。
