电针调控Nrf1/miRNA-15a-5p/NLRP1/Caspase1途径抑制神经元焦亡改善脓毒症后认知功能障碍的作用及机制研究

脓毒症患者存活后中度到重度认知功能障碍发生率增加了3倍左右，给患者、家庭和社会带来极大的负担。通过前期研究发现，电针可以改善脓毒症后认知功能障碍的发生，但具体机制尚不明确。本课题组前期研究表明电针可上调潜在关键分子miR-15a-5p的转录水平，抑制NLRP1炎性小体介导的神经元焦亡；结合生物信息学预测Nrf1为miR-15a-5p的转录调控因子，并且电针促进Nrf1表达。据此，我们提出假设：电针通过激活转录因子Nrf1，促进miRNA-15a-5p的转录，下调NLRP1表达水平，抑制神经元焦亡，从而参与缓解脓毒症后认知功能障碍。本课题拟进一步构建特异感染神经元的AAV病毒，采用扫描电镜、焦亡相关检测、萤光素酶报告基因、RIP等技术，进行转录因子-miRNA和靶基因调控关系以及对神经元焦亡影响的研究，为电针治疗脓毒症后认知功能障碍的临床应用提供理论参考。

The incidence of moderate to severe cognitive dysfunction in patients with sepsis increases by about 3 times, which places a great burden on patients, families and society. According to previous studies, electroacupuncture can improve the occurrence of cognitive dysfunction after sepsis, but the specific mechanism is still unclear. Our previous study showed that electroacupuncture can up-regulate the transcription level of the potential key molecule miR-15a-5p, inhibit NKRP1 inflammatory mediated neuronal pyroptosis; combined with bioinformatics prediction of Nrf1 as miR-15a-5p transcription Regulatory factors, and electroacupuncture promotes Nrf1 expression. Based on this, we hypothesized that electroacupuncture promotes transcriptase Nrf1, promotes transcription of miRNA-15a-5p, down-regulates NLRP1 expression, inhibits neuronal salvation, and participates in the relief of cognitive dysfunction after sepsis. This study intends to further construct AAV virus that specifically infects neurons, and uses scanning electron microscopy, coke-related detection, luciferase reporter gene, RIP and other techniques to regulate transcription factor-miRNA and target gene regulation and influence on neuronal pyroptosis. The study provides a theoretical reference for the clinical application of electroacupuncture in the treatment of cognitive dysfunction after sepsis.