Background: Pulmonary fibrosis (PF) is a chronic and progressive interstitial lung disease. There is no effective treatment for PF. Hepatocyte growth factor (HGF) has anti-inflammatory and antifibrotic effects but has limited potential owing to its short half-life. Methods: To increase the transfection efficiency of pVAX-HGF, we prepared polyethyleneiminepolyethylene glycol: polyethyleneimine/pVAX-HGF (PEG-PEI: PEI/pVAX-HGF) nanocomposite loaded with a plasmid encoding the HGF gene. The PEG-PEI:PEI/pVAX-HGF characteristics, including morphology, particle size, zeta-potential, and DNA entrapment efficiency, were investigated. The pVAX-HGF nanocomposites with low toxicity and high transfection efficiency were screened by cell viability assay and cell transfection. The antifibrotic effect of pVAX-HGF nanocomposite on PF rats induced by bleomycin (BLM) was evaluated by pulmonary function measurement, pathological examination and collagen content assay. Results: Different nanocomposites were prepared to deliver pVAX-HGF, in which mix1 (PEGPEI: PEI/pVAX-HGF) has lower potential and better entrapment ability. PEG-PEI:PEI/pVAX-HGF (N/P=25) nanocomposite with low toxicity and high transfection efficiency was administered to PF rats. After treatment with mix 1/pVAX-HGF, the index of lung function(including EF50, MV, TV, PEF and PIF) in mix 1/pVAX-HGF group was higher than that of the PF group. The number of cells in BALF of the mix 1/pVAX-HGF group was significantly lower than that of the PF groups, and the content of hydroxyproline(HYP) and collagen Type I (Col-I) in the lung of the mix 1/pVAX-HGF group was much lower than that of the PF groups in the early stage. The result of pathological examination showed that rats in the mix1/pVAX-HGF group showed obviously reduced alveolar septal thickening, fewer infiltrated inflammatory cells and less collagen deposition. Conclusion: The PEG-PEI:PEI/pVAX-HGF nanocomposite can ameliorate PF induced by BLM. The pVAX-HGF nanocomposite is a latent therapeutic strategy for PF.

中文翻译：

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纳米复合材料递送的肝细胞生长因子用于基因治疗博来霉素诱导的大鼠肺纤维化

背景：肺纤维化（PF）是一种慢性进行性间质性肺病。PF 没有有效的治疗方法。肝细胞生长因子 (HGF) 具有抗炎和抗纤维化作用，但由于其半衰期短而潜力有限。方法：为了提高 pVAX-HGF 的转染效率，我们制备了聚乙烯亚胺聚乙二醇：聚乙烯亚胺/pVAX-HGF（PEG-PEI：PEI/pVAX-HGF）纳米复合物，该复合物载有编码 HGF 基因的质粒。研究了 PEG-PEI:PEI/pVAX-HGF 的特征，包括形态、粒径、zeta 电位和 DNA 包封效率。通过细胞活力测定和细胞转染筛选出低毒、高转染效率的pVAX-HGF纳米复合材料。通过肺功能测量、病理检查和胶原含量测定评估 pVAX-HGF 纳米复合材料对博来霉素 (BLM) 诱导的 PF 大鼠的抗纤维化作用。结果：制备了不同的纳米复合材料来递送 pVAX-HGF，其中 mix1（PEGPEI：PEI/pVAX-HGF）具有较低的电位和较好的包封能力。将具有低毒性和高转染效率的 PEG-PEI:PEI/pVAX-HGF (N/P=25) 纳米复合材料给予 PF 大鼠。mix 1/pVAX-HGF治疗后，mix 1/pVAX-HGF组的肺功能指标（包括EF50、MV、TV、PEF和PIF）高于PF组。mix 1/pVAX-HGF组BALF细胞数明显低于PF组，mix 1/pVAX-HGF组早期肺组织羟脯氨酸(HYP)和Ⅰ型胶原(Col-I)含量远低于PF组。病理检查结果显示，mix1/pVAX-HGF组大鼠肺泡间隔增厚明显减轻，炎性细胞浸润减少，胶原沉积减少。结论：PEG-PEI:PEI/pVAX-HGF 纳米复合材料可以改善 BLM 诱导的 PF。pVAX-HGF 纳米复合材料是 PF 的潜在治疗策略。PEI/pVAX-HGF 纳米复合材料可以改善 BLM 诱导的 PF。pVAX-HGF 纳米复合材料是 PF 的潜在治疗策略。PEI/pVAX-HGF 纳米复合材料可以改善 BLM 诱导的 PF。pVAX-HGF 纳米复合材料是 PF 的潜在治疗策略。