从circRNA TLK1调控神经元“焦亡-存活”命运研究补肾启智方改善高血压合并脑梗死后认知下降的作用

血管紧张素受体拮抗剂的降压效应不利于卒中急性期治疗，高血压合并脑梗死后认知下降亟待其他有效安全、不影响血压的干预策略。神经元焦亡是脑梗死后认知障碍的关键病机环节，而应激颗粒可促进细胞存活命运，且特异性抑制焦亡。前期临床发现补肾活血法安全有效，补肾启智方可促进自噬体降解（化瘀血以祛邪）抑制炎症小体途径，但对其下游的焦亡机制作用尚不清楚，高通量测序技术发现补肾启智方抑制脑梗死时circRNA TLK1异常表达。据此假设补肾启智方调控circRNA TLK1促进应激颗粒形成（益肾精以扶正），从而抑制焦亡、促进存活以保护认知功能。故以高血压大鼠MCAO模型和HT22海马神经元细胞为研究对象，明确补肾启智方调控circRNA TLK1改善高血压合并脑梗死后认知下降的作用及关键环节，丰富补肾启智方补肾活血的科学内涵，为其提供有力的生物学证据，并为脑梗死后认知障碍的中医药干预方法提供新的思路和理论基础。

The ARBs have an effect of reducing blood pressure，which is not good for the treatment of acute stroke. A more effective and safe treatment for cognitive impairment in "Cerebral infarction with hypertension" patients is needed. Neuron pyroptosis is the key factor leading to PSCI, and stress granules can lead to the cell survival, and specifically inhibit NLRP3 inflammasome activation and pyroptosis. Researches have shown that the therapy of nourishing kidney and activating blood is effective. Bu Shen Qi Zhi recipe can regulate autophagy(activating blood) and NLRP3 inflammasome, and can reduce circRNA TLK1 in MCAO rats. Therefore, the purpose of this study is to explore whether Bu Shen Qi Zhi recipe can regulate circRNA TLK1 to promote the assembly of stress granules (nourishing kidney), so as to inhibit NLRP3-mediated Neuron pyroptosis, promote the survival of neuron and protect cognitive function. This study focus on the SHR MCAO rats and HT22 cells from OGD-induced injury, in order to observe the key targets of the “circRNA TLK1/neuron pyroptosis-live fate” signaling pathway and the effect of Bu Shen Qi Zhi recipe. The result of this study will have important significance to explain the connotation of “Nourishing kidney and Activating blood”, and provide strong biological evidences, new ideas for the effective TCM treatment of PSCI.