整合转录组学、网络药理学及实验验证益气除痰法治疗癌因性疲乏的机制OA

Objective To investigate the therapeutic efficacy of Yiqi Chutan Method(YCM)in treating cancer-related fatigue(CRF)and elucidate its molecular pharmacological mechanisms.Methods A murine model of CRF was established,and the intervention effects of YCM were evaluated through behavioral assessments of fatigue severity.Integrating transcriptomics and network pharmacology to predict the pharmacological targets and potential mechanisms of YCM,with validation through pathological analysis,real-time quantitative reverse transcription-polymerase chain reaction(qRT-PCR),enzyme-linked immunosorbent assay(ELISA),and Western Blot.Results YCM significantly alleviated fatigue in tumor-bearing mice(P＜0.001).Bioinformatic analysis indicated that the pharmacological mechanism of YCM is associated with regulating inflammatory infiltration and fibrosis.Pathological findings verified that YCM could effectively reduce immune cell infiltration in skeletal muscle and preserve the normal structure of skeletal muscle,as well as alleviate skeletal muscle fibrosis.The results of quantitative real-time reverse transcription polymerase chain reaction(qRT-PCR)and enzyme-linked immunosorbent assay(ELISA)confirmed that YCM decreased the levels of inflammatory factors(IL-1B、IL-6、TNF-α)in skeletal muscle(P＜0.05,P＜0.01,P＜0.001).Western Blot results revealed that YCM downregulated the expression of Collagen Ⅰ、Collagen Ⅲ and upregulated matrix metalloproteinases(MMP-2,MMP-4)in skeletal muscle(P＜0.01,P＜0.001).Conclusion YCM effectively alleviates CRF,potentially by reducing inflammatory infiltration in skeletal muscle and mitigating muscle fibrosis.