Lian Xi, Liu Bin, Li Dan, Wang Xinyao, Long Chengbo, Feng Xing, Liao Qiong, Rong Mingqiang
College of Life Sciences, Hunan Normal University, Changsha 410004, China.
Chengdu PDBio Co., Ltd., Chengdu 610225, China.
Toxins (Basel). 2025 Apr 24;17(5):213. doi: 10.3390/toxins17050213.
Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by the fibrotic thickening of the alveolar walls, resulting in compromised gas exchange, restricted ventilation, and respiratory failure. It has been indicated that elastase inhibitors reduced the severity of IPF by neutralizing excessive elastase levels in the lungs. ShSPI is an elastase inhibitor derived from centipede toxin. The present study evaluates the therapeutic effects of ShSPI in a bleomycin-induced idiopathic pulmonary fibrosis model. According to the results, ShSPI markedly reduced the weight loss, showing the improvement of health status in bleomycin-induced mice. Its robust antifibrotic effects were evidenced by the mitigation of alveolar structural damage, reduction in inflammatory cell infiltration, inhibition of collagen deposition, and suppression of fibrotic nodule formation. ShSPI effectively attenuated inflammatory responses by downregulating pro-inflammatory factors (IL-6, IL-1β, and MCP-1) and upregulating the anti-inflammatory factor interleukin-10 (IL-10). After delivered via inhalation, ShSPI exhibited favorable pharmacokinetic properties. It could be detected at 8 h at doses of 1 mg/kg and achieved maximum plasma concentrations (Cmax) of 188.00 ± 64.40 ng/mL in vivo. At high doses (160 mg/kg), ShSPI maintained a strong safety profile, with no detectable toxicity observed. This feature shows the therapeutic potential of ShSPI in the treatment of idiopathic pulmonary fibrosis and provides valuable evidence for its development as a novel peptide-based therapy.
特发性肺纤维化（IPF）是一种慢性肺部疾病，其特征为肺泡壁的纤维化增厚，导致气体交换受损、通气受限和呼吸衰竭。已有研究表明，弹性蛋白酶抑制剂可通过中和肺部过量的弹性蛋白酶水平来减轻IPF的严重程度。ShSPI是一种源自蜈蚣毒素的弹性蛋白酶抑制剂。本研究评估了ShSPI在博来霉素诱导的特发性肺纤维化模型中的治疗效果。结果显示，ShSPI显著减轻了体重减轻，表明博来霉素诱导的小鼠健康状况有所改善。其强大的抗纤维化作用表现为肺泡结构损伤减轻、炎症细胞浸润减少、胶原沉积受到抑制以及纤维化结节形成受到抑制。ShSPI通过下调促炎因子（IL-6、IL-1β和MCP-1）并上调抗炎因子白细胞介素-10（IL-10）有效减轻了炎症反应。经吸入给药后，ShSPI表现出良好的药代动力学特性。在1 mg/kg剂量下，8小时后仍可检测到，在体内达到的最大血浆浓度（Cmax）为188.00±64.40 ng/mL。在高剂量（160 mg/kg）时，ShSPI保持了较强的安全性，未观察到可检测到的毒性。这一特性显示了ShSPI在治疗特发性肺纤维化方面的治疗潜力，并为其作为一种新型基于肽的疗法的开发提供了有价值的证据。
