从致炎细胞因子对下丘脑的影响探讨复方丹参方干预心肌梗死预后的机制

Myocardial infarction (MI) is the most common cause of cardiac morbidity and mortality in many countries, although numerous therapeutic strategies have been developed, death from heart failure is still a serious problem worldwide. Recent studies demonstrated the central nervous system–mediated mechanism has influence on the development of MI. Accumulating evidence suggests that the elevation of Pro-inflammatory cytokines (PIC) plays key roles in the development of MI. It has been reported that compound salvia recipe can influence the prognosis of MI by regulate the expression of PIC. But the mechanism of elevated cytokines in the hypothalamus after MI is unclear. The previous studies have revealed that the brain's vascular endothelial cells and microglia may contribute to the expression of PIC in hypothalamus after MI.So the mechanism responsible for Compound salvia recipe in regulating the expression of PIC may become a therapeutic strategy for MI.. This study is to Produce myocardial infarction rat model, with Compound salvia recipe intervention，measure the expression of PIC in the blood and hypothalamus, evaluate the influence of PIC in the development of MI, and investigate the role and mechanism of compound salvia recipe in the treatment of MI. Frist, in order to investigate the role of compound salvia recipe on the treatment of MI, we examined the expression of PIC in the blood and in the hypothalamus, evaluate the influence of compound salvia recipe on the expression of PIC. And to further study the mechanism of compound salvia recipe on the treatment of MI, we investigate the PGE2 expression and microglia activation in the different time point.

中枢调控机制对心肌梗死预后的影响已成为学术界的共识，中枢靶点也成为心肌梗死治疗的研究热点。最新研究表明，中枢致炎细胞因子（pro-inflammatory cytokine，PIC）表达增高是影响心肌梗死预后的关键环节，复方丹参方对心梗预后的调节作用与PIC密切相关。但循环PIC诱导中枢PIC合成增加，调节心梗预后的具体机制仍不明确。PIC对脑血管内皮细胞、小胶质细胞的影响可能为PIC干预心梗预后的始动及维持因素。. 本课题以心肌梗死大鼠为研究对象，以治疗心梗有效方药复方丹参方为干预手段，以血浆及中枢的PIC在心梗预后中的作用为研究核心。首先，通过探讨下丘脑室旁核与循环PIC表达的相关性及复方丹参方对二者的调控作用，阐明复方丹参方干预心梗预后的可能途径。其次，通过观察复方丹参方对脑血管内皮细胞PGE2的表达、小胶质细胞活化的影响，探讨其调节中枢PIC表达干预心梗预后的可能机制。

1、研究背景：近年来越来越多的临床证据表明，炎症反应在心肌梗死的发生、发展和预后过程中起重要的作用。下丘脑室旁核是大脑的关键神经体液核，参与体内心血管活动的调节。研究表明，下丘脑是中枢影响心肌梗死预后的关键部位。炎症反应可导致下丘脑小胶质细胞激活，合成和释放致炎细胞因子增加。复方丹参方由丹参、三七和冰片组成，研究表明其主要成分中的三七皂苷，人参皂苷可以通过抑制致炎细胞因子的表达，起到神经保护的作用。冰片亦可通过抑制炎性细胞毒性反应所致的神经元损伤，促进神经功能恢复。. 2、研究内容：探讨了下丘脑与循环致炎细胞因子表达的相关性，小胶质细胞活化在致炎细胞因子干预心肌梗死预后中的作用。明确了复方丹参方在心肌梗死后对下丘脑、心肌、血浆致炎细胞因子的调控作用及相关机制，阐述复方丹参方调节中枢干预心梗预后的可能途径。. 3、重要结果：心肌梗死后，心肌组织、血浆、下丘脑致炎细胞因子（IL-6、TNF-α、IL-1β）表达均升高。复方丹参方可以抑制心肌梗后心肌组织、血浆、下丘脑致炎细胞因子（IL-6、TNF-α、IL-1β）的表达，改善心肌梗死大鼠的心脏功能。心肌梗死后下丘脑小胶质细胞激活可能为致炎细胞因子的来源，可能是通过JAK2-STAT3、Notch信号通路介导的。复方丹参方能改善心梗大鼠的心功能及减少心肌细胞凋亡；其可能与抑制致炎细胞因子（IL-6、TNF-α、IL-1β）表达，调节小胶质细胞激活，调控JAK-STAT、Notch信号通路有关。. 4、科学意义：从心肌梗死后心肌、血浆致炎细胞因子（IL-6、TNF-α、IL-1β）与下丘脑致炎细胞因子（IL-6、TNF-α、IL-1β）的表达情况，及致炎细胞因子与小胶质细胞活化的关系及相关机制，复方丹参方的干预节点，部分明确了下丘脑对心肌梗死预后的影响，为中医药治疗心肌梗死提供了新思路。