补肺纳肾丸调控PI3K/AKT信号通路介导的MMP/TIMP平衡减轻慢性阻塞性肺疾病细胞外基质沉积的作用机制OA

This study aimed to investigate the therapeutic effects of Bufei Nashen Pills(BFNSP)on chronic obstructive pulmonary disease(COPD),with a specific focus on whether it acted by modulating the balance between matrix metalloproteinases and tissue inhibitors of metalloproteinases(MMP/TIMP),which was mediated by the phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT)signaling pathway.The main components of BFNSP and its medicated serum were analyzed using liquid chromatography-mass spectrometry(LC-MS).A rat model of COPD was established by cigarette smoke exposure combined with lipopolysaccharide(LPS)injection,and the rats were subsequently treated with different doses of BFNSP.Lung function and histopathological changes in lung tissue were examined.The levels of inflammatory factors and extracellular matrix(ECM)-related indicators(such as MMP-9,MMP-3,TIMP-1,and hyaluronic acid(HA))in bronchoalveolar lavage fluid(BALF)and serum were measured by enzyme-linked immunosorbent assay(ELISA).The expression of collagen Ⅰ,collagen Ⅲ,laminin,key molecules of the PI3K/AKT pathway,MMP-9,and TIMP-1 in lung tissues was detected using immunohistochemistry,reverse transcription-quantitative polymerase chain reaction(RT-qPCR),and Western blot.The research results showed that BFNSP effectively improved lung function,attenuated pathological injury,and reduced inflammatory response in COPD rats.More importantly,it significantly decreased the levels of MMP-9 and MMP-3,and increased the expression of TIMP-1 in both lung tissues and serum,thereby rectifying the MMP/TIMP imbalance and reducing the excessive deposition of ECM components,such as collagen.Mechanistic studies revealed that BFNSP inhibited the phosphorylation of PI3K and AKT in lung tissues.In summary,BFNSP may alleviate ECM deposition and retard the progression of COPD by suppressing the overactivation of the PI3K/AKT signaling pathway and consequently correcting the MMP/TIMP imbalance.