Meakins Christie Laboratories, McGill University Health Centre and McGill University, Montreal, QC, H4A 3J1, Canada.
The Research Institute of the McGill University Health Centre, McGill University, 1001 Decarie Blvd, Office # EM2-3238, Montreal, QC, H4A 3J1, Canada.
Sci Rep. 2023 Nov 23;13(1):20577. doi: 10.1038/s41598-023-47083-y.
Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, immune dysregulation, and multi-organ fibrosis. Interstitial lung disease (ILD) is a complication of SSc and a leading cause of SSc-death. The administration of hypochlorous acid (HOCl) intradermally in the mouse (HOCl-SSc) purportedly shows several features typical of SSc. We studied the model by injecting BALB/c mice daily intradermally with HOCl for 6-weeks, an exposure reported to induce lung fibrosis. On day 42, the skinfold thickness and the dermal thickness were two and three times larger respectively in the HOCl group compared to controls. HOCl treatment did not result in histological features of pulmonary fibrosis nor significant changes in lung compliance. Automated image analysis of HOCl mice lungs stained with picrosirius red did not show increased collagen deposition. HOCl injections did not increase pulmonary mRNA expression of pro-fibrotic genes nor induced the production of serum advanced oxidation protein products and anti-topoisomerase 1 antibodies. Immune cells in bronchoalveolar lavage fluid (BALF) and whole lung digests were not increased in HOCl-treated animals. Since lung fibrosis is proposed to be triggered by oxidative stress, we injected HOCl to Nrf2 mice, a mouse deficient in many antioxidant proteins. Lung compliance, histology, and BALF leukocyte numbers were comparable between Nrf2 mice and wild-type controls. We conclude that the HOCl-SSc model does not manifest SSc-lung disease.
系统性硬化症（SSc）是一种自身免疫性疾病，其特征为血管病变、免疫失调和多器官纤维化。间质性肺病（ILD）是 SSc 的一种并发症，也是 SSc 死亡的主要原因。据称，次氯酸（HOCl）在小鼠中的真皮内给药（HOCl-SSc）表现出几种与 SSc 典型的特征。我们通过每天向 BALB/c 小鼠真皮内注射 HOCl 6 周来研究该模型，据报道这种暴露会引起肺纤维化。在第 42 天，HOCl 组的皮肤褶皱厚度和真皮厚度分别比对照组大 2 倍和 3 倍。HOCl 处理不会导致肺纤维化的组织学特征，也不会导致肺顺应性的显著变化。用苦味酸天狼星红染色对 HOCl 小鼠肺部进行自动图像分析显示胶原沉积没有增加。HOCl 注射不会增加肺纤维化基因的 mRNA 表达，也不会诱导血清晚期氧化蛋白产物和抗拓扑异构酶 1 抗体的产生。HOCl 处理动物的支气管肺泡灌洗液（BALF）和全肺消化液中的免疫细胞没有增加。由于肺纤维化被认为是由氧化应激引发的，我们向 Nrf2 小鼠（一种缺乏许多抗氧化蛋白的小鼠）注射 HOCl。Nrf2 小鼠和野生型对照之间的肺顺应性、组织学和 BALF 白细胞数量没有差异。我们得出结论，HOCl-SSc 模型不会表现出 SSc 肺部疾病。
