解毒祛瘀滋阴方拮抗糖皮质激素致SLE“肠-脑-LTP轴”损伤的作用与机制研究

系统性红斑狼疮（SLE）是以免疫性炎症为突出表现的难治性自身免疫病。目前糖皮质激素仍是治疗SLE的基础药物，但存在明显毒副作用。前期研究发现，解毒祛瘀滋阴方（JP）治疗SLE疗效确切，并能修复糖皮质激素致SLE肠道菌群紊乱及下丘脑-垂体-肾上腺轴（HPA轴）抑制，但作用机制不明。最新研究表明：神经元长时程增强（LPT）损伤与HPA抑制正相关，而NMDA受体是表征LTP损伤的关键因子。预实验发现：JP可以保护SLE小鼠神经系统，并修复糖皮质激素致SLE小鼠LTP损伤。基于此，本课题将从整体与细胞层面研究JP对糖皮质激素致LTP损伤的拮抗作用，通过JP修复SLE小鼠肠道菌群和免疫球蛋白A，改善HPA轴功能，调控Glu/GABA动态平衡及NMDA受体功能变化，阐明JP拮抗糖皮质激素致SLE“肠-脑-LTP轴”损伤作用与机制，为中医治疗SLE提供新思路。

Systemic lupus erythematosus (SLE) is a refractory autoimmune disease characterized by immune inflammation. Currently, glucocorticoid (GC) is still the basic drug for SLE, but there are obvious toxic and effects. Preliminary studies indicated that JieduQuyuZiyin prescription (JP) has a definite therapeutic effect on SLE,and can repair intestinal flora disturbance and hypothalamic-pituitary-adrenal axis (HPA axis) function in SLE induced by GC,but its mechanism is not clear.Recent studies have shown that long-term potentiation (LTP) of hippocampal neurons is positively correlated with HPA inhibition, and NMDA receptor function may be the key factor to characterize the LTP damage. Our preliminary experiments reveal that JP can antagonize the LTP damage induced by GC in SLE mice and repair its nervous system. In this study, synaptic plasticity damage model of SLE mice induced by GC was established from the holistic and cellular level, and then will be administered by JP. We would explore the changes of intestinal flora and secretory immunoglobulin A (SIgA) and HPA axis function inhibition in SLE mice, and to further explore the functional changes of NMDA receptor by combining the dynamic balance of Glu and GABA.Finally, we would clarify the role and mechanism of JP in repairing intestine-brain-LTP damage in SLE mice induced by GC, and provide new ideas for clinical treatment of SLE in Traditional Chinese Medicine.