Alzahrani Badr, Gaballa Mohamed M S, Tantawy Ahmed A, Moussa Maha A, Shoulah Salma A, Elshafae Said M
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka, Saudi Arabia.
Department of Pathology, Faculty of Veterinary Medicine, Benha University, Tukh, Egypt.
J Pathol Transl Med. 2022 Mar;56(2):81-91. doi: 10.4132/jptm.2021.12.27. Epub 2022 Mar 2.
Acute respiratory distress syndrome (ARDS) is one of the most common complications in coronavirus disease 2019 patients suffering from acute lung injury (ALI). In ARDS, marked distortion of pulmonary architecture has been reported. The pulmonary lesions in ARDS include hemodynamic derangements (such as alveolar edema and hemorrhage), vascular and bronchiolar damage, interstitial inflammatory cellular aggregations, and eventually fibrosis. Bleomycin induces ARDS-representative pulmonary damage in mice and rats; therefore, we used bleomycin model mice in our study. Recently, Toll-like receptor 9 (TLR9) was implicated in the development of ARDS and ALI.
In this study, we evaluated the efficiency of a TLR9 blocker (ODN2088) on bleomycin-induced pulmonary damage. We measured the apoptosis rate, inflammatory reaction, and fibroplasia in bleomycin- and bleomycin + ODN2088-treated mice.
Our results showed a significant amelioration in bleomycin-induced damage to pulmonary architecture following ODN2088 treatment. A marked decrease in pulmonary epithelial and endothelial apoptosis rate as measured by cleaved caspase-3 expression, inflammatory reaction as indicated by tumor necrosis factor α expression, and pulmonary fibrosis as demonstrated by Van Gieson staining and α-smooth muscle actin immunohistochemistry were observed following ODN2088 treatment.
All these findings indicate that blocking downstream TLR9 signaling could be beneficial in prevention or mitigation of ARDS through hemodynamic derangements, inflammation, apoptosis, and fibrosis.
急性呼吸窘迫综合征（ARDS）是2019冠状病毒病患者发生急性肺损伤（ALI）时最常见的并发症之一。据报道，ARDS患者肺部结构明显扭曲。ARDS的肺部病变包括血流动力学紊乱（如肺泡水肿和出血）、血管和细支气管损伤、间质炎症细胞聚集，最终导致纤维化。博来霉素可在小鼠和大鼠中诱导出具有ARDS代表性的肺损伤；因此，我们在研究中使用了博来霉素模型小鼠。最近，Toll样受体9（TLR9）被认为与ARDS和ALI的发生发展有关。
在本研究中，我们评估了TLR9阻断剂（ODN2088）对博来霉素诱导的肺损伤的作用效果。我们检测了博来霉素处理组和博来霉素+ODN2088处理组小鼠的细胞凋亡率、炎症反应和纤维组织增生情况。
我们的结果显示，ODN2088处理后，博来霉素诱导的肺结构损伤得到显著改善。通过检测裂解的半胱天冬酶-3的表达发现，肺上皮和内皮细胞凋亡率显著降低；通过检测肿瘤坏死因子α的表达发现，炎症反应减轻；通过Van Gieson染色和α平滑肌肌动蛋白免疫组化发现，肺纤维化程度减轻。
所有这些发现表明，阻断下游TLR9信号传导可能有助于通过改善血流动力学紊乱、炎症、细胞凋亡和纤维化来预防或减轻ARDS。
