Zhang Yan, Xu Liping, Chen Qiang, Guan Tianrong, Lin Na, Xu Danyang, Lu Lihong, Dai Qiaoding, Song Xinwei
Department of Rheumatism and Immunology, The First Affiliated Hospital of Zhejiang Chinese Medical University/Zhejiang Provincial Hospital of Traditional Chinese Medicine, No. 54 Youdian Road Shangcheng District, Hangzhou, Zhejiang 310006, China.
Department of Orthopedics, Affiliated Xiaoshan Hospital, Hangzhou Normal University, No. 728 Yucai North Road Xiaoshan District, Hangzhou, Zhejiang 311200, China.
Evid Based Complement Alternat Med. 2022 Apr 13;2022:6557486. doi: 10.1155/2022/6557486. eCollection 2022.
Interstitial lung disease (ILD) is an important complication of systemic sclerosis (SSc). The aim of this study was to investigate the effect and possible mechanism of polypeptide extract of scorpion venom (PESV) on SSc-ILD.
C57/BL6 mice were injected with bleomycin to establish a SSc-ILD model. Different concentrations of PESV solution were administered to SSc-ILD mice, and dexamethasone was used as a positive control. H&E staining and Masson staining were used to observe the pathological changes. The TGF-1 expression level was detected by immunohistochemistry. The expression of epithelial-mesenchymal transition (EMT)-related proteins was detected by Western blot, and the expression of TGF-1/Smad pathway-related proteins was also detected. The content of inflammatory cytokines in serum and BALF was determined by ELISA.
Pathological analysis showed that PESV could alleviate SSc-ILD-induced pulmonary inflammation and fibrosis. Compared with the model group, the content of inflammatory cytokines IL-6 and TNF- significantly decreased after PESV treatment. PESV could increase the expression of epithelial marker (E-cadherin) and reduce the expression of interstitial markers (collagen I, vimentin, N-cadherin, and a-SMA). In addition, PESV could reduce the expression level of TGF-1/Smad pathway-related protein.
PESV can attenuate SSc-ILD by regulating EMT, and the effect was linked to the TGF-1/Smad signaling pathway, which indicated that PESV may serve as a candidate drug for SSc-ILD.
间质性肺疾病（ILD）是系统性硬化症（SSc）的一种重要并发症。本研究旨在探讨蝎毒多肽提取物（PESV）对SSc-ILD的作用及其可能机制。
给C57/BL6小鼠注射博来霉素以建立SSc-ILD模型。将不同浓度的PESV溶液给予SSc-ILD小鼠，并使用地塞米松作为阳性对照。采用苏木精-伊红（H&E）染色和Masson染色观察病理变化。通过免疫组化检测转化生长因子-β1（TGF-β1）表达水平。采用蛋白质印迹法检测上皮-间质转化（EMT）相关蛋白的表达，同时检测TGF-β1/Smad信号通路相关蛋白的表达。采用酶联免疫吸附测定（ELISA）法测定血清和支气管肺泡灌洗液（BALF）中炎性细胞因子的含量。
病理分析显示，PESV可减轻SSc-ILD引起的肺部炎症和纤维化。与模型组相比，PESV治疗后炎性细胞因子白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）的含量显著降低。PESV可增加上皮标志物（E-钙黏蛋白）的表达，并降低间质标志物（Ⅰ型胶原、波形蛋白、N-钙黏蛋白和α-平滑肌肌动蛋白）的表达。此外，PESV可降低TGF-β1/Smad信号通路相关蛋白的表达水平。
PESV可通过调节EMT减轻SSc-ILD，其作用与TGF-β1/Smad信号通路有关，这表明PESV可能成为治疗SSc-ILD的候选药物。
