蒙古族药山沉香流分I的抗小鼠心肌缺血药效评价及作用机制

Pharmacological evaluation of Mongolian medicine Syringa pinnatifolia fraction I against acute myocardial ischemia in mice

特色蒙古族药山沉香,具有抑赫依、清热、止痛等功效,主治赫依性心刺痛、心悸心烦、失眠等症。其乙醇总提物(T)及主要部位(M)具有抗心肌缺血作用,机制与调控环氧合酶(COX)介导的炎症途径及p53介导的凋亡途径相关。在此基础上,该研究首先对M部位进行化学分割,得到流分I和M3,采用小鼠心肌缺血模型评价M,I,M3的药效。结果显示,与模型组相比,流分I与M部位均能显著降低各组小鼠的左心室舒张末内径(LVEDd)和左心室收缩末内径(LVEDs),显著升高左心室射血分数(EF)和短轴缩短率(FS),降低血清中上升的肌酸激酶同工酶(CK-MB)和乳酸脱氢酶(LDH)含量,减弱心肌炎症浸润,减轻纤维化和胶原沉积程度,提示M和I具有相同程度的抗心肌缺血作用,而M3无此效果。相关机制研究提示I能剂量依赖性降低心肌组织中COX-1,COX-2,p53蛋白的表达。此研究为进一步的化学分割和药效物质群阐明奠定基础,为后续充分发挥系统生物学手段解析山沉香抗心肌缺血的药效物质铺路。

Syringa pinnatifolia Hemsl.( SP) is a representative Mongolian folk medicine with the effects of inhibiting Heyi related diseases,clearing heat and relieving pain. It has been used for the treatment of Heyi-induced heart tingling,heart palpitations,upset,insomnia and other symptoms. Total ethanol extract( T) and major fraction( M) of SP have been evaluated its anti-ischemic effects,and the mechanism was related to the regulation of cyclooxygenase( COX)-mediated inflammatory pathway and p53-mediated apoptosis pathway in our previous studies. This study reports the chemical fractionation on M by which to obtain subfractions( I and M3),and the pharmacological evaluation of M,I,and M3 against myocardial ischemia in mice. The result showed that I and M reduced the values of LVEDd and LVEDs,significantly increased EF and FS values,increased serum CK-MB and LDH levels in mice,and reduced in inflammatory cells infiltration and collagen deposition in the infarcted myocardial tissue,suggesting that M and I possess the same degree anti-myocardial is chemia equally whereas M3 has no this effect. Related mechanism studies suggested that I can reduce the expression of COX-1,COX-2 and p53 protein in myocardial tissue in a dose-dependent manner. This study lays the foundation for further chemical segmentation and clarification of pharmacological substance groups,paving the way for the full use and benefits to be use of systematic biological methods to analyze the pharmacological basis of SP against myocardial ischemia.