基于NF-κB炎症通路介导的细胞焦亡探讨电针对缺血性脑卒中后神经再生的作用机制

Ischemic stroke (CIS) secondary Nerve inflammatory lesion is an important cause of severe disease, high disability rate and nerve function recovery. The research group recently discovered that PRG5 inhibits RhoA to inhibit the secretion of inflammatory cytokines, and the regulation of RhoA/ PRG5 by electroacupuncture and the large vertebral cavity reduces the inflammatory damage and promotes nerve regeneration. But inflammation RohA/ROS to the NF-kappa B pathway mediated inflammatory cells Cell pyroptosis to nerve injuries affect, and whether the curative through regulating the NF-kappa B inhibiting inflammatory Cell pyroptosis alleviate nerve injuries, in turn, promote the nerve regeneration, these new scientific questions not clear. Cell pyroptosis as the breakthrough point, this topic with cells from the NF-kappa B signal transduction pathways of inflammation, with the aid of molecular biotechnology gene silencing: ①Detection of RhoA, ROS, NLRP3, caspase 1, clear Electroacupuncture Cell pyroptosis effect and mechanism against cells; ②The NF-kappa B gene silence, detect inflammesome related proteins, clear Cell pyroptosis the neurological effects inflammatory injury and the curative effect; ③The effects of electroacupuncture dynamic observation on the growth and nerve repair of filamentous pseudopod and axon were observed, and the preliminary experimental data were provided for the reduction of CIS Nerve inflammatory lesions by electroacupuncture.

缺血性脑卒中（CIS）继发神经炎性损伤是导致病损严重、致残率高和神经功能恢复困难的重要原因。课题组近期发现PRG5阻遏RhoA抑制炎性因子分泌，电针百会、大椎穴调控RhoA/PRG5减轻神经炎性损伤继而促进神经再生。但RohA/ROS对NF-κB炎症通路介导细胞焦亡致神经炎性损伤有何影响，以及电针是否通过调控NF-κB抑制细胞焦亡减轻神经炎性损伤进而促进神经再生，这些新的科学问题不清楚。本课题以细胞焦亡为切入点，从NF-κB炎症信号转导的途径入手，借助基因沉默等分子生物技术：①检测RhoA、ROS、NLRP3、caspase-1，明确电针对细胞焦亡作用与机制；②沉默NF-κB基因，检测inflammesome相关蛋白，明确细胞焦亡对神经炎性损伤影响及电针作用；③动态观察电针对丝状伪足和轴突生长及神经修复影响，为电针减轻CIS神经炎性损伤促进神经再生提供前期实验数据。

缺血性脑卒中（CIS）继发神经炎性损伤是导致病损严重、致残率高和神经功能恢复困难的重要原因。本项目利用分子生物学和信号转导的研究手段，通过电针督脉百会、大椎穴不同时程调控NF-κB信号通路介导细胞焦亡(pyroptosis)对缺血性脑卒中后神经炎性损伤与内源性神经再生作用及其机理展开研究。我们发现NF-κB炎症通路活化NLRP3，进而促进caspase-1的激活，诱导细胞焦亡。NF-κB通路在介导抑制性信号对轴突再生的抑制过程中起着关键作用。电针可下调MCAO缺血再灌注后海马区NF-κB及Caspase-1蛋白的表达。MCAO组海马区NF-κB、Caspase-1蛋白表达明显增加，再灌注后1d和7d表达均升高；电针百会、大椎穴可抑制NF-κB的表达从而抑制MCAO模型大鼠缺血灶炎症信号通路上相关蛋白的表达，因此，电针可下调MCAO缺血再灌注后海马区NF-κB、Caspase-1蛋白的表达并诱导轴突生长和促进eNSCs增殖分化，从而起到促进神经再生的作用。以上研究详细阐明电针对脑卒中神经损伤和修复的炎症机理，为脑卒中的临床治疗提供理论依据和潜在的治疗靶点。