Therapeutic effects of Xingren Baihe nano-formulation on bleomycin-induced pulmonary fibrosis in rats
杏仁百合方纳米制剂对博来霉素诱导的大鼠肺纤维化的治疗作用

摘要

目的 探讨杏仁百合纳米制剂对肺纤维化模型大鼠的保护作用，并从肺功能、组织病理学、炎症反应及纤维化相关基因表达等多个层面评价其疗效。方法 建立博来霉素诱导的大鼠肺纤维化模型，将15只大鼠随机分为正常对照组、模型组和给药组。给药组给予杏仁百合纳米制剂干预。通过检测大鼠肺功能指标（呼气峰流速、潮气量），HE染色处理后，观察肺组织形态学变化并进行Szapiel和Ashcroft评分，采用ELISA法检测支气管肺泡灌洗液中炎症因子（IL-18、IL-6、TNF-α）水平，利用实时荧光定量PCR技术检测肺组织中Ⅰ型胶原（Col-Ⅰ）和α-平滑肌肌动蛋白（α-SMA）的mRNA表达水平。结果 与正常对照组相比，模型组大鼠PEF、VT显著降低（P<0.01），肺组织结构破坏严重，炎症浸润和纤维化明显，Szapiel和Ashcroft评分显著升高，BALF中IL-18、IL-6、TNF-α水平及肺组织Col-Ⅰ、α-SMA mRNA表达均显著上调（P<0.01）。与模型组相比，给药组大鼠PEF、VT显著升高（P<0.01），肺组织病理损伤明显改善，Szapiel和Ashcroft评分显著降低（P<0.01），BALF中各炎症因子水平及肺组织中Col-Ⅰ、α-SMA mRNA表达均显著下调（P<0.05或P<0.01）。结论 杏仁百合纳米制剂能有效改善肺纤维化模型大鼠的肺功能，减轻肺组织炎症反应和病理损伤，其作用机制可能与抑制炎症因子释放和下调Col-Ⅰ、α-SMA等纤维化关键基因的表达有关，表明该制剂具有良好的抗肺纤维化应用前景。

Abstract

Objective To investigate the protective effects of Xingren Baihe nano-formulation on rats with pulmonary fibrosis and to evaluate its therapeutic efficacy from multiple perspectives, including pulmonary function, histopathology, inflammatory response, and the expression of fibrosis-related genes.
Methods A rat model of pulmonary fibrosis was induced by bleomycin. The fifteen rats were randomly divided into a normal control group, a model group, and a treatment group. The treatment group was administered with the Xingren Baihe nano-formulation. Pulmonary function indicators, including peak expiratory flow (PEF) and tidal volume (VT), were measured. Histopathological changes in lung tissues were observed after HE staining and scored using the Szapiel and Ashcroft scales. The levels of inflammatory cytokines (IL-18, IL-6, TNF-α) in bronchoalveolar lavage fluid (BALF) were detected by ELISA. The mRNA expression levels of Collagen type I (Col-Ⅰ) and alpha-smooth muscle actin (α-SMA) in lung tissue were assessed using quantitative real-time PCR.
Results Compared with the normal control group, the model group exhibited significantly reduced PEF and VT (P<0.01), severe destruction of lung tissue structure with marked inflammatory infiltration and fibrosis, significantly higher Szapiel and Ashcroft scores, and significantly upregulated levels of IL-18, IL-6, and TNF-α in BALF, as well as increased mRNA expression of Col-Ⅰ and α-SMA in lung tissue (P<0.01). Compared with the model group, the treatment group showed significantly increased PEF and VT (P<0.01), markedly improved pathological lung damage, significantly reduced Szapiel and Ashcroft scores (P<0.01), and significantly downregulated levels of the aforementioned inflammatory cytokines and the mRNA expression of Col-Ⅰ and α-SMA (P<0.05 or P<0.01).
Conclusion   The Xingren Baihe nano-formulation effectively improved pulmonary function and alleviated inflammatory responses and pathological damage in rats with pulmonary fibrosis. Its mechanism of action may be associated with the inhibition of inflammatory cytokine release and the downregulation of key fibrotic genes such as Col-Ⅰ and α-SMA, indicating that this formulation holds promising potential for anti-pulmonary fibrosis therapy.