基于T细胞受体CDR3编码基因测序探讨电针治疗慢性前列腺炎/慢性盆底疼痛综合症的免疫调节相关机制研究
批准号:
82105037
项目类别:
青年科学基金项目(C类)
资助金额:
30.0 万元
负责人:
吴佳霓
依托单位:
学科分类:
中医针灸学
结题年份:
2024
批准年份:
2021
项目状态:
已结题
项目参与者:
吴佳霓
中文摘要
慢性前列腺炎/慢性盆底疼痛综合症(CP/CPPS)是泌尿系最常见疾患,与自身免疫炎症相关,主要表现为长期反复的骨盆区疼痛及不同程度的尿频急尿痛等。研究表明T细胞参与了CP/CPPS的疾病进程,而TCR CDR3及CD4+CD25+Treg与T细胞功能直接相关。目前尚无免疫组库的方法探索其病理和治疗机制。本研究团队前期临床试验及循证学研究显示电针治疗CP/CPPS有效,优于假针。因此,电针可能通过调节TCR CDR3基因序列表达以及CD4+CD25+Treg比例,进一步调节T细胞的功能状态,从而发挥其临床抑制免疫性炎症的作用。本研究采用高通量测序技术,对CP/CPPS患者治疗前后外周血TCR CDR3测序,探索电针有效性与TCR CDR3多样性关系;同时,通过构建自身免疫性前列腺炎大鼠,观察电针前后大鼠外周血及前列腺组织CD4+CD25+Treg比例及FOXP3、相关细胞因子的表达水平。
英文摘要
Chronic prostatitis/chronic pelvic floor pain syndrome (CP/CPPS) is the most common disease of the urinary system, which is associated with autoimmune inflammation, mainly manifested by the long-term and repeated pelvic pain and varied degrees of urinary urgency, frequency and pain. Studies have shown that T cells are involved in the process of CP/CPPS, and TCR CDR3 and CD4+CD25+Treg are directly related to the function of T cells. However, there are no immune repertoire methods to explore the pathology and therapeutic mechanism of CP/CPPS. Our previous clinical trials and evidence-based studies have shown that electro-acupuncture was effective for CP/CPPS, and superior to sham electro-acupuncture. Therefore, electro-acupuncture might regulate the function of T cells through regulating the expression of TCR CDR3 gene sequence and the proportion of CD4+CD25+Treg; thus, to exert its clinical effect of inhibiting immune inflammation. In this study, the high throughput sequencing technology will be used to test the TCR CDR3 sequence in the peripheral blood of CP/CPPS patients before and after treatment, in order to explore the relationship between the effectiveness of electro-acupuncture and the diversity of TCR CDR3. Meanwhile, the proportion of CD4+CD25+Treg, the expression of FOXP3 and related cytokines in peripheral blood and prostate tissue of rats with autoimmune prostatitis will be observed before and after treatment.
目前,针刺治疗慢性前列腺炎/慢性盆腔疼痛综合征(CP/CPPS)的有效性和安全性已经被国内外医学界认可,但无论是进一步提高针刺对CP/CPPS的临床疗效,还是准确评价针刺的作用机制,都迫切需要揭示其生物学基础。确定针刺治疗CP/CPPS的科学机制,建立治疗有效性的系统数据,挖掘免疫细胞分子激活层面在此过程中的病理生理学作用是实现目标的关键。有鉴于此,本研究结合免疫组库方法,定量刻画基因的表达转录情况,也能够通过与患者自身主观症状评价NIH-CPSI评分相互印证,进一步揭示针刺对于CP/CPPS起效的生物学基础,进而改变针刺临床研究评价方式受患者主观性大,安慰剂效应模糊不清的现状,实现对针刺生物学基础的深入挖掘和揭示内在联系。综和国内外相关研究及本研究团队前期研究基础,我们提出如下假说:免疫组库的多样性可能与CP/CPPS的发生发展密切相关,针刺可能通过调节CD4+CD25+Treg的比例以减轻EAP大鼠炎症反应和疼痛。研究结果表明:1)CP/CPPS患者外周血TCR CDR3的免疫组库多样性减少,在CP/CPPS患者中,我们发现S100A9和S100A8的表达显著上调,为CP/CPPS的病理机制提供了重要线索,也可能进一步成为未来诊断和治疗的新靶点;2)针刺治疗可以调节CP/CPPS患者外周血TCR CDR3免疫组库多样性;3)针刺治疗可以增加EAP大鼠CD4+CD25+Treg的比例,调节相关细胞因子水平,抑制前列腺的免疫炎性反应。
国内基金
海外基金