Department of Physiology, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.
Department of Pulmonary and Critical Care Medicine, Kyung Hee University Hospital at Gangdong, Seoul 05278, Republic of Korea.
Int Immunopharmacol. 2020 Jun;83:106444. doi: 10.1016/j.intimp.2020.106444. Epub 2020 Mar 29.
Acute lung injury (ALI) is characterized by disruption of the alveolar-capillary membrane resulting in pulmonary edema and accumulation of associated proteinaceous alveolar exudate. Initiation of ALI upregulates tumor necrosis factor-α (TNF-α), which activates nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPK) that induce various pro-inflammatory mediators. Polydexyribonucleotide (PDRN) is an adenosine A receptor agonist that exerts anti-inflammatory effects by suppressing the production of pro-inflammatory cytokines and apoptosis. We investigated the therapeutic efficiency of PDRN on ALI induced by lipopolysaccharide (LPS) in rats. ALI was induced by intratracheal instillation of LPS (5 mg/kg) in 200 μL saline. The PDRN treatment group received a single intraperitoneal injection of 500 μL saline including PDRN (8 mg/kg) 1 h after ALI induction. To confirm the involvement of the adenosine A receptor in PDRN, 8 mg/kg 7-dimethyl-1-propargylxanthine (DMPX) was applied with PDRN treatment. Rats were then sacrificed 12 h after PDRN and DMPX treatments. Intratracheal administration of LPS caused lung tissue damage and significantly increased the lung injury scores and levels of pro-inflammatory cytokines, and apoptotic factors. In addition, MAPK/NF-κB signaling factors were increased by ALI initiation. PDRN treatment potently suppressed expressions of MAPK/NF-κB signaling factors compared to the PDRN + DMPX co-treated group. These alterations led to a reduction of pro-inflammatory cytokines, apoptotic factors, and NF-κB and MAPK signaling, which promoted the recovery of damaged lung tissue. PDRN therapy demonstrated therapeutic effects for LPS-induced ALI compared to the non-treated and DMPX-treated groups. Therefore, PDRN may be used as a therapy for initial treatment of ALI.
急性肺损伤（ALI）的特征是肺泡毛细血管膜破裂，导致肺水肿和相关蛋白性肺泡渗出物积聚。ALI 的发生会上调肿瘤坏死因子-α（TNF-α），进而激活核因子-κB（NF-κB）和丝裂原活化蛋白激酶（MAPK），诱导各种促炎介质的产生。聚脱氧核糖核苷酸（PDRN）是一种腺苷 A 受体激动剂，通过抑制促炎细胞因子和细胞凋亡的产生发挥抗炎作用。我们研究了 PDRN 对脂多糖（LPS）诱导的大鼠 ALI 的治疗效果。通过气管内滴注 LPS（5mg/kg）生理盐水（200μL）诱导 ALI。PDRN 治疗组在 ALI 诱导后 1 小时，给予 500μL 含 PDRN（8mg/kg）的生理盐水腹腔注射。为了确认 PDRN 涉及腺苷 A 受体，应用 8mg/kg 7-二甲基-1-丙炔黄嘌呤（DMPX）与 PDRN 治疗联合使用。然后，在 PDRN 和 DMPX 治疗后 12 小时处死大鼠。气管内给予 LPS 导致肺组织损伤，并显著增加肺损伤评分和促炎细胞因子、凋亡因子的水平。此外，MAPK/NF-κB 信号通路因子在 ALI 发生时增加。与 PDRN+DMPX 联合治疗组相比，PDRN 治疗显著抑制了 MAPK/NF-κB 信号通路因子的表达。这些变化导致促炎细胞因子、凋亡因子、NF-κB 和 MAPK 信号的减少，促进了受损肺组织的恢复。与未治疗组和 DMPX 治疗组相比，PDRN 治疗对 LPS 诱导的 ALI 具有治疗作用。因此，PDRN 可能可用于治疗 ALI 的初始治疗。
