解毒祛瘀滋阴方调控IDO1/KYN色氨酸代谢通路诱导Treg分化治疗SLE的机制研究

系统性红斑狼疮的目前治疗仍以糖皮质激素为主，但其副作用会使患者的继发感染率达到27%，并成为其死亡的重要原因之一。SLE患者中存在着吲哚胺2,3-双加氧酶1/犬尿氨酸(IDO1/KYN)的色氨酸代谢通路异常与Th17/Treg的免疫失衡。前期多项临床研究证实解毒祛瘀滋阴方治疗SLE可以起到增效解毒的作用。实验研究发现解毒祛瘀滋阴方可以对异常的色氨酸代谢进行修复，可以调节Th17/Treg的免疫平衡。在前期研究的基础上，我们推测解毒祛瘀滋阴方通过调控IDO1/KYN的色氨酸代谢通路来诱导Treg细胞的分化，减少Th17炎症性细胞及代谢毒物KYN的累积，达到免疫调节的作用。本课题拟运用流式细胞术、HPLC-MS及血清药理学、CRISPR/Cas9等技术方法观察解毒祛瘀滋阴方调控IDO1/KYN色氨酸代谢通路诱导Treg分化的作用机制，以揭示解毒祛瘀滋阴方防治SLE的作用机制，并指导临床应用。

The current treatment of systemic lupus erythematosus (SLE) is still dominated by glucocorticoids, but the side effects of excessive immunosuppression can cause the patient's secondary infection rate to reach 27%, and become one of the important causes of death. There were abnormalities in the tryptophan metabolism pathway of indoleamine 2,3-dioxygenase 1 (IDO1)/ kynurenine (KYN) and immune imbalance of Th17/Treg in SLE patients. Our previous clinical studies confirmed that the treatment of SLE with Jieduquyuziyin prescription (JP) can effectively reduce disease activity, reduce the amount of glucocorticoids used, and reduce side effects. JP can repair abnormal tryptophan metabolism and regulate the balance of Th17/Treg in SLE patients. On the basis of previous research, we speculate that JP can induce the differentiation of Treg cells by regulating the IDO1/KYN tryptophan metabolism pathway in SLE patients, and reduce the accumulation of Th17 inflammatory cells and metabolic toxins like KYN, and achieve immunomodulatory effects. In this study, we intend to use flow cytometry, HPLC-MS and serum pharmacology, CRISPR/Cas9 and other technical methods to analyze the relationship between tryptophan metabolism and immune balance, and to observe the regulation of IDO/1KYN and Treg differentiation by JP, so as to reveal the mechanism of JP in preventing and treating SLE and guide its clinical application.