Abstract：
The pathogenesis of recurrent oral ulcers (ROU) is complex, with a long duration of illness and challenging to cure. According to traditional Chinese medicine (TCM),\"heat accumulation in the heart-spleen\" is one of the main causative factors. Jiaweidaochi powder (JWDCP) is based on the ancient Chinese medicine formula JWDCS, with the addition of Tongcao and gypsum and the removal of Mu Tong. It is generally used to treat \"heat accumulation in the heart-spleen.\" Previous studies have demonstrated that it effectively reduces recurrence rates and is anti-inflammatory in modulating immunity. The ROU rats\' model for JWDCP intervention treatment had been established, and histological tests revealed that JWDCP has a therapeutic effect on the pathological changes in the oral mucosa. In addition, the methylation levels of peripheral blood IFNG gene were detected by bisulfite sequencing PCR (BSP), and the methylation levels of the IFNG promoter region in the model group and each dose group were lower than those in the control group. However, no significant methylation differences were observed. Furthermore, the results of enzyme-linked immunosorbent assay (ELISA) and RNA quantitative polymerase chain reaction showed that JWDCP could reduce IFN-γ and IL-4 protein concentrations, with high GATA-3 mRNA production, T-bet mRNAproduction was upgraded, elevated IL-4 mRNA levels, and reduced IFN-γ mRNA levels after treatment (P < 0.001). The expression of transcription factor T-betmRNA and GATA-3 gene mRNA was accompanied by changes in IFN-γmRNA and IL-4mRNA, demonstrating that Th2 type differentiation in RAS suppresses the body\'s immunity and that the imbalance of transcription factor expression further leads to Th1/Th2 drift. JWDCP is likely to reduce the protein concentration by regulating the imbalance of transcription factors and enhancing antioxidant capacity, thus achieving therapeutic effects. Treatment of recurrent oral ulcer models is not sufficient to reset IFNG methylation levels, correlating with the refractoriness of ROU, further confirming the complexity of epigenetic mechanisms and that epigenetic alterations in specific mediators may persist locally.
摘要：
复发性口腔溃疡(ROU)的发病机制复杂,疾病持续时间长，难以治愈。根据中医（TCM），“心脾积热”是主要的致病因素之一。加味道赤散（JWDCP）是基于古代中药配方JWDCS，随着通草和石膏的添加和木通的去除。它通常用于治疗心脏脾脏中的热量积累。“以前的研究表明，它可以有效降低复发率，并且在调节免疫力方面具有抗炎作用。建立了JWDCP干预治疗的ROU大鼠模型，组织学检查表明，JWDCP对口腔粘膜的病理变化具有治疗作用。此外,采用亚硫酸氢盐测序PCR(BSP)检测外周血IFNG基因甲基化水平,模型组及各剂量组IFNG启动子区甲基化水平均低于对照组。然而,未观察到显著的甲基化差异。此外，酶联免疫吸附试验(ELISA)和RNA定量聚合酶链反应结果显示,具有高GATA-3mRNA产量，T-betmRNAproduction升级了，IL-4mRNA水平升高，治疗后IFN-γmRNA水平降低(P<0.001)。转录因子T-betmRNA和GATA-3基因mRNA的表达伴随IFN-γmRNA和IL-4mRNA的变化,证明RAS中Th2型分化抑制机体免疫，转录因子表达失衡进一步导致Th1/Th2漂移。JWDCP可能通过调节转录因子的失衡和增强抗氧化能力来降低蛋白质浓度,从而达到治疗效果。复发性口腔溃疡模型的治疗不足以重置IFNG甲基化水平，与ROU的折射相关，进一步证实了表观遗传机制的复杂性,以及特定介质的表观遗传改变可能在局部持续.
