基于“自噬-凋亡交互作用”对血管内皮微环境稳态的影响探讨化痰通络法对急性脑梗死溶栓后脑侧支循环的调节效应与机制

Ischemia/reperfusion injury after thrombolysis for acute cerebral infarction could inhibit the building and opening of collateral circulation, leading to irreversible damage to nerve cells. The mechanism might be involved with endothelial cell injury and vascular microenvironment imbalance mediated by "crosstalk between autophagy and apoptosis", which lead to increase the cerebral microcirculation dysfunction. In previous study, we found that Huatan Tongluo method could reduce ischemia/reperfusion injury, and adaptively protect nerve cells by regulating endoplasmic reticulum steady-state. Based on that, we use MCAO rats as observed objects, with Huatan Tongluo method medicine, from the "overall macro" and "micro-elements" view, to observe the recovery of neurological defects in MACO rats; LASCA to observe cerebral artery microcirculation status; while to observe morphology changes of vascular endothelial cells, with HPLC, CoIp, and Western Blot to observe related factors of the steady-state of microenvironment and the key factor protein expression of " crosstalk between autophagy and apoptosis", to explore the mechanism of Huatan Tongluo method to regulate cerebral microcirculation after thrombolysis for acute cerebral infarction, to supply its experimental basis to promote nerve cell function recovery by protecting endothelial cells, and to provide evidence for the application of Chinese medicine in the treatment of acute critical illness.

急性脑梗死溶栓后易继发缺血再灌注损伤，可严重阻碍大脑侧支循环的建立与开放，进而影响神经功能的恢复。目前研究显示，其机制可能与“自噬—凋亡交互作用”所介导的血管内皮细胞损伤及其微环境稳态失衡，进而加重大脑微循环障碍有关。课题组前期发现，化痰通络法具有减轻缺血再灌注损伤，调控内质网稳态进而适应性保护神经细胞的作用。基于此，本研究拟采用MCAO大鼠，通过化痰通络法中药干预，从“宏观整体”与“微观分子”相结合角度，观察其促进神经功能缺损恢复情况，LASCA技术观察大脑侧支循环建立及血流状况，同时观察血管内皮细胞微观形态变化。进一步结合HPLC、WB和CoIp技术观察血管内皮微环境稳态相关因子及“自噬—凋亡交互作用”中关键蛋白表达，以期初步探讨化痰通络法调节急性脑梗死溶栓后侧支循环的作用机制，充实其通过保护血管内皮细胞以达到促进神经细胞功能恢复的实验依据，为中医药在急危重症治疗中的应用提供部分证据。