Yu Jia-Wang, Lu Wei-Hua
The Fifth Clinical Medical College of Anhui Medical University, Hefei, 230032, China.
EICU, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, 241000, China.
Iran J Basic Med Sci. 2025;28(4):426-433. doi: 10.22038/ijbms.2024.81986.17740.
The present study investigated the protective effect of melittin (MEL) against bleomycin (BLM)- induced pulmonary fibrosis (PF) in mice and the mechanism underlying this effect.
A mouse model of PF was established by intratracheal injection of 3.5 mg/kg BLM. Twenty-four hours after the model was established, the mice in the treatment groups were intraperitoneally injected with MEL, and specimens were collected 28 days later. The body weight, survival rate, and pulmonary index (PI) of the mice were determined. Haematoxylin and eosin (HE) staining, Masson's trichrome staining, immunohistochemical staining, kit assays, and Western blot (WB) analysis were performed.
Our study indicated that MEL significantly increased the body weight and survival rate, reduced PI, and improved lung histopathology in mice. In addition, MEL inhibited epithelial-mesenchymal transition (EMT) and extracellular matrix (ECM) deposition. Attenuated mitochondrial damage and reduced oxidative stress (OS) were also observed in MEL-treated mice. We further showed that MEL inhibited the TGF-β1/Smad2/3 pathway and activated the AMPK/SIRT1/PGC-1α pathway.
MEL is a promising future therapeutic agent for PF. Its multifaceted and complex mechanism of action inhibits both EMT and ECM production by modulating the TGF-β1/Smad2/3 pathway. It also improves mitochondrial function and reduces OS at least partially through the activation of the AMPK/SIRT1/PGC-1α signaling pathway.
本研究探讨蜂毒肽（MEL）对博来霉素（BLM）诱导的小鼠肺纤维化（PF）的保护作用及其作用机制。
通过气管内注射3.5mg/kg BLM建立PF小鼠模型。模型建立24小时后，给治疗组小鼠腹腔注射MEL，28天后采集标本。测定小鼠的体重、存活率和肺指数（PI）。进行苏木精-伊红（HE）染色、Masson三色染色、免疫组织化学染色、试剂盒检测和蛋白质免疫印迹（WB）分析。
我们的研究表明，MEL显著增加小鼠体重和存活率，降低PI，并改善肺组织病理学。此外，MEL抑制上皮-间质转化（EMT）和细胞外基质（ECM）沉积。在MEL处理的小鼠中还观察到线粒体损伤减轻和氧化应激（OS）降低。我们进一步表明，MEL抑制TGF-β1/Smad2/3信号通路并激活AMPK/SIRT1/PGC-1α信号通路。
MEL是一种有前景的PF治疗药物。其多方面和复杂的作用机制通过调节TGF-β1/Smad2/3信号通路抑制EMT和ECM产生。它还至少部分地通过激活AMPK/SIRT1/PGC-1α信号通路改善线粒体功能并降低OS。
