源于中医辟谷理论的隔日限食疗法抑制NF-κB介导急性脊髓损伤炎症反应机制的实验研究

Curing spinal cord injury (SCI) is still a big challenge. The inflammatory response is a major component of secondary injury in acute SCI that plays a key role in mediating the pathogenesis. BIGU, a method from Traditional Chinese Medicine, is very important in prevention and treatment of diseases. Our previous study discovered that every-other-day fasting (EODF), which is form of an intermittent BIGU, had a neuroprotective effect in animal models with acute SCI, and can improve functional recovery; Meanwhile, our recent preliminary experiment also discovered that EODF can significantly inhibit inflammation after acute SCI. However, the pathway for the mechanism of anti-inflammation and the effective time window for application of this intervention are not yet clear. The new study shows that EODF can reduce inflammation response and tissue damage caused by brain ischemia through the direct inhibition of IKK/NF-κB signaling pathway. Our overall hypothesis is that EODF can reduce inflammation reactions by inhibiting the IKK/NF-κB signaling pathways activation and regulating expression of downstream proteins to produce neuroprotective effects after acute SCI. In this study, we will study how long we can delay EODF treatment after acute SCI，which still remains effective through the assessment of animal behavior and histology. We will also identify the gene expression profiles associated with inflammation and NF-κB pathway, expression of NF-κB and downstream proteins. We hope that the findings will demonstrate the clinically relevant time window of such intervention as well as its physiopathologic mechanism, in order to provide solid preclinical evidence for this noninvasive, no-cost treatment, and to develop the clinical application of BIGU theory.

脊髓损伤（SCI）尚无有效治疗手段，炎症在其病理生理进程中处于中心地位。辟谷作为中医养生术，在防病治病中有重要作用。我们前期研究证实大鼠急性SCI后予隔日限食（EODF）这种间断辟谷法有显著神经保护作用并促进患肢功能恢复，预实验也证实其对急性SCI抗炎效应。但EODF介入时机对疗效影响，其通过何种信号传导通路抗炎而达到神经保护作用尚不清楚。最新研究表明，EODF可通过抑制NF-κB信号通路激活降低脑缺血的炎症反应和组织损伤。由此，我们假设：EODF治疗急性SCI可能通过抑制IKKβ激酶活性，抑制NF-κB通路激活并调节其下游蛋白表达达到抗炎及神经保护作用。本项目拟建立大鼠SCI模型，采用不同时机EODF干预，评价行为学、组织学、NF-κB信号通路相关基因表达、IKK/NF-κB信号通路激活及下游蛋白表达，探讨EODF治疗SCI最佳干预时机及机制，促进EODF临床转化，拓展辟谷临床应用潜力。

脊髓损伤（SCI）尚无有效治疗手段，炎症在其病理生理进程中处于中心地位。辟谷作为中医养生术，在防病治病中有重要作用。我们前期研究证实大鼠急性SCI后予隔日限食（EODF）这种间断辟谷法有显著神经保护作用并促进患肢功能恢复，预实验也证实其对急性SCI抗炎效应。但EODF介入时机对疗效影响，其通过何种信号传导通路抗炎而达到神经保护作用尚不清楚。最新研究表明，EODF可通过抑制NF-κB信号通路激活降低脑缺血的炎症反应和组织损伤。由此，我们假设：EODF治疗急性SCI可能通过抑制IKKβ激酶活性，抑制NF-κB通路激活并调节其下游蛋白表达达到抗炎及神经保护作用。本项目拟建立大鼠SCI模型，采用不同时机EODF干预，评价行为学、组织学、NF-κB信号通路相关基因表达、IKK/NF-κB信号通路激活及下游蛋白表达，探讨EODF治疗SCI最佳干预时机及机制，促进EODF临床转化，拓展辟谷临床应用潜力。