Yang Fangyong, Du Wenjing, Tang Zhao, Wei Ying, Dong Jingcheng
Department of Integrative Medicine, Huashan Hospital, Fudan University, No. 12 Middle Wulumuqi Road, Jing'an District, Shanghai, 200040, China.
Institutes of Integrative Medicine, Fudan University, Shanghai, China.
Chin Med. 2023 Mar 30;18(1):33. doi: 10.1186/s13020-023-00730-y.
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing lung disease with high mortality. Inflammation and epithelial mesenchymal transformation (EMT) may play an important role in the occurrence and development of IPF. Qing-Re-Huo-Xue formula (QRHXF) has been used clinically by our team for half a century and has obvious therapeutic effects on lung disease. Nevertheless, the role and mechanism of QRHXF in the treatment of IPF have never been studied.
A mouse pulmonary fibrosis model was established by intratracheal injection of BLM. The effects of QRHXF on the treatment of pulmonary fibrosis were studied by pulmonary function testing, imaging examination, pathological staining, transmission electron microscopy (TEM) observation and mRNA expression. Tandem mass tag (TMT)-based quantitative proteomics was carried out to analyse the lung protein expression profiles between the control (CTL), bleomycin (BLM) and QRHXF (BLM + QRHXF) groups. Immunohistochemistry and qRT-PCR were used to verify the possible existence of drug target proteins and signalling pathways.
The results of pulmonary function, lung pathology and imaging examinations showed that QRHXF could significantly alleviate BLM-induced pulmonary fibrosis in vivo. Additionally, inflammatory cell infiltration and EMT were markedly reduced in BLM-induced PF mice administered QRHXF. Proteomics detected a total of 35 proteins, of which 17 were upregulated and 18 were downregulated. A total of 19 differentially expressed proteins (DEPs) overlapped between the BLM versus CTL groups and the BLM + QRHXF versus BLM groups. The expression of p53 and IGFBP3 was reversed in the QRHXF intervention group, which was verified by immunohistochemistry and qRT-PCR.
QRHXF attenuated BLM-induced pulmonary fibrosis, and regulation of the p53/IGFBP3 pathway might be associated with its efficacy, which holds promise as a novel treatment strategy for pulmonary fibrosis patients.
特发性肺纤维化（IPF）是一种慢性、进行性纤维化肺病，死亡率高。炎症和上皮-间质转化（EMT）可能在IPF的发生发展中起重要作用。清热活血方（QRHXF）由我团队临床应用已近半个世纪，对肺部疾病有显著治疗效果。然而，QRHXF治疗IPF的作用及机制尚未见研究报道。
通过气管内注射博来霉素（BLM）建立小鼠肺纤维化模型。通过肺功能检测、影像学检查、病理染色、透射电子显微镜（TEM）观察及mRNA表达研究QRHXF对肺纤维化的治疗作用。采用基于串联质谱标签（TMT）的定量蛋白质组学分析对照组（CTL）、博来霉素（BLM）组和QRHXF（BLM+QRHXF）组之间的肺蛋白表达谱。采用免疫组织化学和qRT-PCR验证药物靶蛋白和信号通路的可能存在情况。
肺功能、肺病理和影像学检查结果显示，QRHXF可显著减轻体内BLM诱导的肺纤维化。此外，给予QRHXF的BLM诱导的PF小鼠炎症细胞浸润和EMT明显减少。蛋白质组学共检测到35种蛋白质，其中17种上调，18种下调。BLM与CTL组以及BLM+QRHXF与BLM组之间共有19种差异表达蛋白（DEP）重叠。免疫组织化学和qRT-PCR验证了QRHXF干预组中p53和IGFBP3的表达得到逆转。
QRHXF减轻了BLM诱导的肺纤维化，p53/IGFBP3通路的调节可能与其疗效相关，有望成为肺纤维化患者的一种新的治疗策略。
