温肺化纤汤对肺纤维化模型大鼠肺功能及HMGB1/TLR4/NF-κB信号通路的影响

doi:10.3969/j.issn.1006-6233.2025.04.06

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摘要 目的: 探讨温肺化纤汤(WFHX)对肺纤维化(PF)模型大鼠肺功能及高迁移率族蛋白B1(HMGB1)/Toll样受体4(TLR4)/核因子κB(NF-κB)信号通路的影响。方法: 采用博来霉素(BLM)诱导构建特发性肺纤维化(IPF)大鼠,将建模成功的大鼠分为,Model组、L-WFHX、M-WFHX、H-WFHX(0.18、0.54、0.9mg/3mL的WFHX灌胃)、WFHX+LPS组(灌胃0.9mg/3mL的WFHX+0.4mg/kg LPS),每组各10只,另选择10只大鼠为Control组(采用生理盐水诱导),Model组和Control组腹灌胃和注射等量生理盐水,每天灌胃3次,注射一次,连续28d。检测各组大鼠肺功能;HE染色和Masson染色检测大鼠肺组织损伤;免疫组化检测肺组织中α-SMA、collagenⅠ的表达;ELISA检测肺组织中TGF-β1、IL-1β表达;Western blot检测大鼠肺组织中HMGB1、TLR4、NF-κB蛋白的表达。结果: Control组肺组织结构清晰完整,无明显炎症细胞浸润和胶原纤维沉积;Model组肺组织结构明显破坏,可见大量炎症细胞浸润和胶原沉积;L-WFHX、M-WFHX、H-WFHX组肺组织结构明显改善,炎性渗出和胶原沉积减少;WFHX+LPS组肺组织结构明破坏加重,炎性渗出和胶原沉积增多。Model组FEV0.4/FVC、Szapiel评分、Ashcroft评分、α-SMA、collagenⅠ、TGF-β1、IL-1β、HMGB1、TLR4、NF-κB表达高于Control组,FVC、MassFVC低于Control组(P<0.05);L-WFHX、M-WFHX、H-WFHX组FEV0.4/FVC、Szapiel评分、Ashcroft评分、α-SMA、collagenⅠ、TGF-β1、IL-1β、HMGB1、TLR4、NF-κB表达低于Model组,FVC、MassFVC高于Model组(P<0.05);WFHX+LPS组FEV0.4/FVC、Szapiel评分、Ashcroft评分、α-SMA、collagenⅠ、TGF-β1、IL-1β、HMGB1、TLR4、NF-κB表达高于H-WFHX组,FVC、MassFVC低于H-WFHX组(P<0.05)。结论: WFHX可以改善PF大鼠的肺功能,其机制可能是抑制HMGB1/TLR4/NF-κB信号通路实现的。

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	田辉
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关键词 ：肺纤维化, 温肺化纤汤, 高迁移率族蛋白B1, Toll样受体4, 核因子κB

Abstract：Objective: To investigate the effects of Wenfei Huaxian decoction (WFHX) on lung function and the high mobility group protein B1 (HMGB1)/Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway in pulmonary fibrosis (PF) model rats. Methods: Idiopathic pulmonary fibrosis (IPF) was induced in rats using bleomycin (BLM).Successfully modeled rats were divided into the Model group,L-WFHX group (0.18 mg/3mL WFHX),M-WFHX group (0.54mg/3mL WFHX),H-WFHX group (0.9mg/3mL WFHX),and WFHX+LPS group (0.9mg/3mL WFHX + 0.4mg/kg LPS),with 10 rats in each group.Another 10 rats were selected as the Control group (induced with physiological saline).The Model and Control groups were orally gavaged (three times daily) and injected (once daily) with an equal amount of physiological saline for 28 consecutive days.Lung function was assessed in all groups.Lung tissue injury was evaluated using HE staining and Masson staining.Immunohistochemistry was used to detect the expression of α-smooth muscle actin (α-SMA) and collagen I in lung tissue.Enzyme-linked immunosorbent assay (ELISA) was used to measure the expression of transforming growth factor-β₁ (TGF-β₁) and interleukin-1β (IL-1β) in lung tissue.Western blot was used to detect the expression of HMGB1,TLR4,and NF-κB proteins in rat lung tissue. Results: The Control group showed clear and intact lung tissue structure with no significant inflammatory cell infiltration or collagen fiber deposition.The Model group exhibited significant lung tissue damage,with extensive inflammatory cell infiltration and collagen deposition.The L-WFHX,M-WFHX,and H-WFHX groups showed significant improvement in lung tissue structure,with reduced inflammatory exudation and collagen deposition.The WFHX+LPS group exhibited aggravated lung tissue damage,with increased inflammatory exudation and collagen deposition.Compared to the Control group,the Model group showed higher FEV0.4/FVC,Szapiel score,Ashcroft score,α-SMA,collagen I,TGF-β1,IL-1β,HMGB1,TLR4,and NF-κB expression,and lower FVC and MassFVC (P<0.05).Compared to the Model group,the L-WFHX,M-WFHX,and H-WFHX groups showed lower FEV0.4/FVC,Szapiel score,Ashcroft score,α-SMA,collagen I,TGF-β1,IL-1β,HMGB1,TLR4,and NF-κB expression,and higher FVC and MassFVC (P<0.05).Compared to the H-WFHX group,the WFHX+LPS group showed higher FEV0.4/FVC,Szapiel score,Ashcroft score,α-SMA,collagen I,TGF-β1,IL-1β,HMGB1,TLR4,and NF-κB expression,and lower FVC and MassFVC (P<0.05). Conclusion: WFHX can improve lung function in PF rats,and its mechanism may involve the inhibition of the HMGB1/TLR4/NF-κB signaling pathway.

Key words： Pulmonary fibrosis Wenfei Huaxian decoction High mobility group protein B1 Toll-like receptor 4 Nuclear factor-kappa B

基金资助:湖北省武汉市中医药科研项目立项任务书,(编号:WZ22C58)

通讯作者: 付桃利

引用本文:

田辉, 付桃利, 王丽梅, 黄胤. 温肺化纤汤对肺纤维化模型大鼠肺功能及HMGB1/TLR4/NF-κB信号通路的影响[J]. 河北医学, 2025, 31(4): 564-570.
TIAN Hui, FU Taoli, WANG Limei, et al. The Effect of Wenfei Huaxian Decoction on Lung Function and HMGB1/TLR4/NF-κB Signaling Pathway in Pulmonary Fibrosis Model Rats. HeBei Med, 2025, 31(4): 564-570.

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http://www.hbyxzzs.cn/CN/10.3969/j.issn.1006-6233.2025.04.06 或 http://www.hbyxzzs.cn/CN/Y2025/V31/I4/564

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