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Dynamic experimental study on the effect of Shenqi Chongcao Formula on immune tandem reaction in IPF model rats based on the MAPK/ERK/Nrf2 signal pathway
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DOI   10.11656/j.issn.1673-9043.2024.08.08
Key Words   Shenqi Chongcao Formula;idiopathic pulmonary fibrosis;immune response;macrophage;HAN Mingxiang
Author NameAffiliationE-mail
WANG Sanfeng Anhui University of Chinese Medicine, Hefei 230038, China  
CHEN Wei The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei 230031, China 1642214473.qq.com 
HE Cheng Anhui University of Chinese Medicine, Hefei 230038, China  
LUAN Jun Anhui University of Chinese Medicine, Hefei 230038, China  
Abstract
    [Objective] To observe the effect of Chinese medical master HAN Ming-xiang' Shenqi Chongcao Formula on the idiopathic pulmonary fibrosis(IPF) rats based on the mitogen activated protein kinase(MAPK)/extracellular regulated protein kinases(ERK)/nuclear factor-erythroid 2-related factor 2(Nrf2) signal pathway. [Methods] 150 Specific Pathogen-Free(SPF)-grade Sprague-Dawley(SD) rats were randomly and evenly divided into 5 groups:the blank group,the model group,Shenqi Chongcao group,Pirfenidone group and the inhibitor of nuclear factor erythroid 2-related factor 2(Nrf2) group. IPF rat models were established except the blank group,then 6~8 rats in each group were weighed and euthanized on the 7th,14th,21st,and 28th days of the experiment. Hematoxylin-eosin(HE) and Masson staining were used to observe the pathological changes in the lung tissues;ELISA method was used to detect the contents of nuclear Nrf2 and heme oxygenase-1(HO-1) in the rats,serum;Reverse Transcription-Polymerase Chain Reaction(RT-PCR) was used to detect the expression levels of mitogen-activated protein kinase 1(MEK1),mitogen-activated protein kinase 2(MEK2),extracellular regulated protein kinases 1(ERK1),extracellular regulated protein kinases 2(ERK2) and adaptor protein complex-1(AP-1) mRNA in the rats,lung tissues;Flow cytometry was used to detect the positive rates of M1 and M2 macrophages,and then M1/M2 was calculated to evaluate the immune response level. [Results] Compared with the blank group and at the same time,on the 14th,21st,and 28th days,the other four groups of rats showed lower weight;on the 7th,14th,21st,and 28th days,the four groups of rats showed varying degrees of inflammatory cell infiltration,collagen fiber deposition in the lung tissue,and higher contents of Nrf2 and HO-1 in the serum,higher expression levels of MEK1,MEK2,ERK1,ERK2 and AP-1 mRNA in the lung tissues. Compared with the model group,on the 14th,21st,and 28th days,the other three groups showed higher weight;on the 7th,14th,21st,and 28th days,the three groups showed milder lesion severity,lower contents of Nrf2 and HO-1,and lower expression levels of MEK1,MEK2,ERK1,ERK2,AP-1 mRNA(P<0.05). Compared with the blank group,the lung tissue M1/M2 of the model group rats was significantly higher in the early stage(P<0.05),and in the late stage it was significantly lower(P<0.05). Compared with the model group,in the early stage the other three groups had significantly lower M1/M2(P<0.05),and in the late stage had significantly higher M1/M2(P<0.05). [Conclusion] Shenqi Chongcao Formula can reduce the degree of pulmonary fibrosis in rats like Pirfenidone and the inhibitor of Nrf2. The mechanism maybe that Shenqi Chongcao Formula can reduce the expression levels of AP-1 and HO-1 by inhibiting MAPK/ERK/Nrf2 signaling pathway,thereby interving the immune reaction in the lungs of IPF rats,reducing inflammatory response and collagen deposition,and delaying the progress of pulmonary fibrosis.

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