前列消汤干预自身免疫性前列腺炎IL-6-JAK2-STAT3信号通路调控CD4+T细胞凋亡及分化的研究

CP is a common chronic inflammatory disease of refractory genitourinary system in young and middle-aged men. Research found that the autoimmune response of CD4+T cells to Th17 cell differentiation imbalance is an important etiology of CP. IL-6 mediate JAK2-STAT3 pathway can lead to CD4+T cells apoptosis resistance and differentiation into Th17 cells. Therefore, the excessive prolongation of IL-6 signal may be the main cause of CP delay. Ours Previous studies showed that Qianlianxiao decoction was effective in the treatment of CP, which could reduce the expression of IL-6 and IL-17A in prostate of EAP mice and inhibit the differentiation of Th17 cells. Based on these, we have come up with hypotheses that Qianlianxiao decoction can regulate the apoptosis and differentiation of CD4+T cells in EAP model by interfering with IL-6-JAK2-STAT3 pathway, so as to inhibit the differentiation of Th17 cells and reduce its autoimmune reaction. In this study, Qianlianxiao decoction was used to interfere with EAP mice, With JAK2 inhibitor AG490 as positive control, the mechanism of Qianliesxiao decoction regulating the apoptosis and differentiation of CD4+T cells through the intervention of IL-6-JAK2-STAT3 pathway was clarified from molecular, cell, tissue and animal level.Hope to provide experimental basis for the study of CP.

慢性前列腺炎（CP）是中青年男性一种常见的难治性泌尿生殖系慢性炎症疾病。研究发现CD4+T细胞偏向Th17细胞分化失衡所致的自身免疫反应是CP的重要病因；IL-6介导的JAK2-STAT3通路可使CD4+T细胞产生凋亡抵抗、并向Th17细胞分化，IL-6信号过度延长可能是CP迁延难愈的主要原因。前期研究发现前列消汤治疗CP疗效确切，可降低EAP小鼠前列腺IL-6和IL-17A的表达、抑制Th17细胞分化。据此提出假说：前列消汤可通过干预IL-6-JAK2-STAT3通路调控EAP模型CD4+T细胞凋亡及分化，从而抑制Th17细胞分化、降低其自身免疫反应程度。本课题拟用前列消汤干预EAP小鼠，以JAK2抑制剂AG490为阳性对照，从分子、细胞、组织以及动物水平明确前列消汤通过干预IL-6-JAK2-STAT3通路调控CD4+T细胞凋亡及分化的作用机制。以期为中医药防治CP的研究提供实验依据。

慢性前列腺炎（CP）是中青年男性常见的难治性泌尿生殖系慢性炎症疾病。研究发现CD4+T细胞偏向Th17细胞分化失衡所致的自身免疫反应是CP的重要病因；IL-6介导的JAK2-STAT3通路可使CD4+T细胞产生凋亡抵抗、并向Th17细胞分化，IL-6信号过度延长可能是CP迁延难愈的主要原因。前期研究发现前列消汤治疗CP疗效确切，可降低EAP小鼠前列腺IL-6和IL-17A的表达、抑制Th17细胞分化。据此提出假说：前列消汤可通过干预IL-6-JAK2-STAT3通路调控EAP模型CD4+T细胞凋亡及分化，从而抑制Th17细胞分化、降低其自身免疫反应程度。.课题主要研究前列消汤干预EAP小鼠模型降低炎症反应与IL-6-JAK2-STAT3通路调控是否存在关联。在体实验研究：检测前列消汤对EAP模型小鼠前列腺组织IL-6、gp130、JAK2、STAT3、SOCS3、RORγt、IL-17A、Foxp3的表达水平。离体实验研究：检测CD4+T细胞活性及纯度，检测bcl-2、Caspase-9的表达水平及含药血清对基质细胞增殖与毒性。.在体研究表明前列消汤与JAK2拮抗剂均能不同程度下调EAP模型小鼠前列腺IL-6、gp130、JAK2、STAT3、SOCS3、RORγt、IL-17A、Foxp3表达，以中/高剂量组较为显著，说明前列消汤通过IL-6-JAK2-STAT3通路抑制自身免疫性前列腺炎症反应，进而改善EAP小鼠前列腺病理结构及自身免疫反应功能；离体研究表明前列消汤与JAK2拮抗剂均能不同程度下调EAP模型小鼠前列腺CD4+T细胞中凋亡相关因子bcl-2、Casp9表达，说明前列消汤对CD4+T细胞凋亡抵抗及分化有一定作用。.综上所述，前列消汤能较好缓解EAP模型小鼠炎症反应，结合前期研究证实，前列消汤作用机制与调节IL-6-JAK2-STAT3通路、调控前列腺CD4+T细胞凋亡抵抗及分化相关，为后期利用siRNA验证前列消汤调控下游核转录因子效应表现，以及中医药防治EAP提供相关参考科学依据。