基于CYP3A4基因多态性探讨雷公藤调控PI3K/AKT信号通路治疗类风湿关节炎疗效差异的分子机制

雷公藤治疗类风湿关节炎（RA）的疗效得到医学界的公认，但存在个体疗效差异始终是制约雷公藤治疗RA的一大难题。本课题组前期在中医从毒论治RA理论指导下，揭示CYP3A4基因rs2740574位点单核苷酸多态性（SNP）与雷公藤治疗RA的个体疗效差异存在关联，但其疗效差异的分子机制尚未阐明。研究表明，PI3K/AKT信号通路在RA炎症及自噬机制中发挥重要的作用。因此，本课题拟在中医从毒论治RA理论指导下，通过全基因组相关研究测序CIA大鼠CYP3A4基因rs2740574位点SNP，运用HE染色、酶联免疫吸附剂测定、实时荧光定量PCR、蛋白免疫印迹等方法检测多种炎症因子及自噬蛋白的表达水平，透射镜下观察组织的自噬小体，探讨基于CYP3A4基因rs2740574位点SNP，雷公藤调控PI3K/AKT信号通路治疗RA的抗炎及抑制自噬分子机制，以期为雷公藤治疗RA的个体化用药与精准医疗进行新的探索。

The clinical curative effect of Tripterygium wilfordii Hook F in the treatment of rheumatoid arthritis (RA) has been recognized by the medical community, but the uneven curative effect has always been a major problem restricting the treatment of RA.Under the guidance of the theory of toxicity in traditional Chinese medicine, our research group previously revealed that the single nucleotide polymorphism (SNP) of CYP3A4 gene rs2740574 was associated with individual therapeutic effect differences in the treatment of RA by Tripterygium wilfordii Hook F, but the molecular mechanism of the therapeutic effect differences has not been clarified.In addition, studies have shown that PI3K/ Akt signaling pathway plays an important role in the mechanisms of inflammation and autophagy in rheumatoid arthritis.Therefore, under the guidance of the theory of toxicity in traditional Chinese medicine,Through genome-wide related studies, the SNP at rs2740574 site of CYP3A4 gene in CIA rats was sequenced, and the expression levels of various inflammatory factors and autophagy proteins were detected by HE staining, ELISA assay, real-time fluorescence quantitative PCR, Western blot and other methods, the autophagosomes of the tissue were observed under transmission microscope.To explore the anti-inflammatory and autophagy inhibition molecular mechanism of Tripterygium wilfordii Hook F regulating PI3K/ Akt signaling pathway in the treatment of RA based on SNP of CYP3A4 gene rs2740574.To explore the anti-inflammatory and autophagy inhibition molecular mechanism of Tripterygium wilfordii Hook F regulating PI3K/ Akt signaling pathway in the treatment of RA based on SNP of CYP3A4 gene rs2740574.In order to make new exploration for the individualized medication and precision medicine of Tripterygium wilfordii Hook F in the treatment of RA.