首页|基于TGF-β1/JNK信号通路探讨补肺益气通络方治疗特发性肺纤维化的作用机制

基于TGF-β1/JNK信号通路探讨补肺益气通络方治疗特发性肺纤维化的作用机制

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目的 基于转化生长因子-β1(TGF-β1)/c-Jun氨基末端激酶(JNK)信号通路探讨补肺益气通络方治疗特发性肺纤维化(IPF)的作用机制.方法 网络药理学富集分析关键靶点,构建IPF大鼠模型,分为空白对照组、IPF模型组及补肺益气通络方组.观察各组肺组织病理变化,分析支气管肺泡灌洗液(BALF)中WBC水平,ELISA检测血清、BALF、肺组织中肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、磷酸化JNK(p-JNK)/JNK、TGF-β1、基质金属蛋白酶组织抑制因子-1(TIMP-1)、基质金属蛋白酶-9(MMP-9)等蛋白表达水平,RT-PCR检测血清、BALF、肺组织中p-JNK/JNK、TGF-β1、TIMP-1、MMP-9等mRNA表达水平.结果 网络药理学的富集分析结果显示,TGF-β1和JNK信号通路与IPF密切相关.与IPF模型组比较,补肺益气通络方组的肺组织有序性提高,实变范围减少,纤维组织增生明显减少,BALF中WBC水平和TNF-α、IL-6表达水平降低.与空白对照组相比,IPF模型组血清、BALF和肺组织中TGF-β1、p-JNK/JNK、TIMP-1、MMP-9及其mRNA表达水平升高,差异有统计学意义(P<0.05);补肺益气通络方对模型大鼠进行干预后,除血清中MMP-9表达水平和BALF中TGF-β1、血清中TIMP-1、肺组织中MMP-9 mRNA表达水平无差异,其他指标均降低(P<0.05).结论 补肺益气通络方对IPF的治疗作用可能与其调控TGF-β1/JNK信号通路相关.
Action mechanism of Bufei Yiqi Tongluo formula in treating idiopathic pulmonary fibrosis based on TGF-β1/JNK signaling pathway
Objective To investigate the action mechanism of Bufei Yiqi Tongluo formula in treating id-iopathic pulmonary fibrosis (IPF) based on the transforming growth factor-β1 (TGF-β1)/c-Jun N-terminal ki-nase (JNK) signaling pathway.Methods The key targets of network pharmacology conducted the enrichment analysis and the IPF rat model was constructed,which was divided into the blank control group,IPF model group and Bufei Yiqi Tongluo formula group.The pathological changes of lung tissue in various groups were observed,and the levels of white blood cells (WBC) in bronchoalveolar lavage fluid (BALF) were analyzed. The enzyme-linked immunosorbent assay (ELISA) was used to detect the protein expression levels of tumor necrosis factor-α (TNF-α),interleukin-6 (IL-6),phosphorylated JNK (p-JNK)/JNK,TGF-β1,tissue inhibitor of metalloproteinases-1 (TIMP-1) and matrix metalloproteinase-9 (MMP-9) in serum,BALF and lung tissue. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the mRNA expression levels of these proteins in serum,BALF and lung tissue.Results The network pharmacology enrichment analysis re-sults revealed that TGF-β1 and JNK signaling pathways were closely related with IPF.Compared with the IPF model group,the lung tissue orderliness in the Bufei Yiqi Tongluo formula group was increased,the consolida-tion range was decreased,the fibrotic tissue proliferation was significantly reduced,the WBC level and expres-sion levels of TNF-α and IL-6 in BALF were significantly decreased.Compared with the blank control group,the mRNA expression levels of TGF-β1,p-JNK/JNK,TIMP-1 and MMP-9 in serum,BALF and lung tissues in the IPF model group were increased with statistical difference (P<0.05).After the intervention on the model rats by the Bufei Yiqi Tongluo formula,except there was no difference in the expression level of MMP-9 pro-tein in serum,TGF-β1 in BALF,TIMP-1 in serum and MMP-9 mRNA in lung tissue,but the other indicators were decreased (P<0.05).Conclusion The therapeutic effect of Bufei Yiqi Tongluo formula in IPF may be related to its regulation on the TGF-β1/JNK signaling pathway.

network pharmacologyBufei Yiqi Tongluo formulaidiopathic pulmonary fibrosisTGF-β1/JNK signaling pathway

白文梅、李风森

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新疆医科大学附属中医医院呼吸科,乌鲁木齐 830000

网络药理学 补肺益气通络方 特发性肺纤维化 TGF-β1/JNK信号通路

新疆维吾尔自治区卫生健康青年医学科技人才专项项目新疆维吾尔自治区青年拔尖人才项目

WJWY-20222920232112215

2024

重庆医学
重庆市卫生信息中心,重庆市医学会

重庆医学

CSTPCD
影响因子:1.797
ISSN:1671-8348
年,卷(期):2024.53(16)