基于cAMP/PKA/CREB通路的淫羊藿女贞子配伍抗哮喘大鼠气道炎症机制研究OA

Objective Aimed to investigate the therapeutic effect and molecular mechanism of Folium Epimedii(FE)and Fructus Ligustri Lucidi(FLL)on airway inflammation in asthmatic rats based on the cAMP/PKA/CREB signaling pathway.Methods Specific pathogen-free(SPF)male SD rats were randomLy divided into a control group,an asthma model group(asthma group),an FE group,a FLL group,and a combination group(FE+FLL),with 6 rats in each group.An asthma model was established by ovalbumin sensitiza-tion and challenge,and the intervention groups received intragastric administration for 2 weeks.Enzyme-linked immunosorbent assay(ELISA)was used to detect immunoglobulin E(IgE),interleukin-6(IL-6),malondialdehyde(MDA),and superoxide dismutase(SOD)levels in lung tissue and serum,as well as cyclic adenosine monophosphate(cAMP),phosphorylated protein kinase A(p-PKA),total PKA,phosphorylated cAMP-response element binding protein(p-CREB),and total CREB expression levels.Western blot(WB)was used to detect protein expression,and quantitative real-time polymerase chain reaction(qRT-PCR)was used to detect related mRNA levels.Results Compared with the control group,the asthma group showed significantly increased levels of IgE,IL-6,and MDA in lung tissue(P<0.01 or P<0.05),significantly decreased SOD activity(P<0.01),significantly downregulated expres-sion of proteins and mRNAs related to the cAMP/PKA/CREB pathway,and significantly decreased ratios of p-PKA/PKA and p-CREB/CREB(P<0.01 or P<0.05).Compared with the model group,the FE,FLL,and FE+FLL intervention groups all significantly reduced IgE,IL-6,and MDA levels and increased SOD activity(P<0.01 or P<0.05).They also upregulated the expression of pro-teins and mRNAs related to the cAMP/PKA/CREB pathway,with the combination group showing the most significant effect(P<0.01).The FE and FE+FLL groups showed more pronounced increases in the p-CREB/CREB ratio,while the FE,FLL,and FE+FLLgroups all significantly increased the p-PKA/PKA ratio.Conclusion The combination of FE and FLL can exert a synergistic anti-inflammatory effect and alleviate asthmatic airway inflammation by downregulating inflammatory factors,reducing oxidative stress,and activating the cAMP/PKA/CREB signaling pathway.This suggests its potential application value as a traditional Chinese medicine(TCM)compound for intervening in asthma.