复方阿魏酸对实验性大鼠脑缺血再灌注损伤的保护作用

背景脑缺血卒中的病理机制复杂,实施"鸡尾酒"方案可能是有前途的研究.目的研究复方阿魏酸对实验性大鼠脑缺血再灌注损伤的保护作用,并探讨其作用机制.设计完全随机设计、对照实验研究. 地点和材料本研究地点为重庆医科大学第二临床学院,健康成年Wistar大鼠由重庆医科大学实验动物中心提供. 干预采用大鼠双侧颈总动脉阻断和尾部放血并重复缺血再灌注的脑缺血模型,分别给予生理盐水、丹参药液或复方阿魏酸药液灌胃5 d. 主要观察指标大鼠脑组织内皮素-1( Endothelin-1, ET-1)、降钙素基因相关肽(Calcitonin gene-related peptide, CGRP)、丙二醛、能量代谢、热休克蛋白 70(heat shock protein 70,HSP70)表达及病理组织学的观察. 结果模型组 ET-1、丙二醛含量最高,CGRP最低,存在能量代谢紊乱.复方阿魏酸高剂量组脑组织 [ET-1( 0.73±0.04) ng/g]、乳酸 [( 16.28± 1.1)μ mol/g]、丙二醛 [( 116.8± 7.55) nmol/g]含量明显降低,ATP[( 18.22± 0.83)μ g/g],CGRP[( 1.62± 0.13) ng/g]、 Na+-K+-ATP酶活性 [( 747.82±63.94) nkat]显著升高,与模型组相比,差异有显著性意义 (P< 0.05).复方阿魏酸的以上作用存在量效关系,其高剂量组优于阳性对照药物丹参.复方阿魏酸治疗组大脑皮层HSP70 表达明显增强,大脑缺血损伤程度有减轻. 结论复方阿魏酸对脑缺血再灌注损伤具有保护作用,其机制与改善脑细胞能量代谢、拮抗自由基、改善微循环等多环节作用有关.

Protection of compound ferulic acid against cerebral ischemic reperfusion injury in experimental rats

BACKGROUND:Because of the complex pathological mechanism of ischemic stroke,the research on cocktail plan is prospective probably. OBJECTIVE:To study the protection of compound ferulic acid against cerebral ischemic reperfusion injury in experimental rats and to explore its function mechanism. DESIGN:A completely randomized controlled trial. SETTING and MATERIALS:The trial was carried out in the Second Clinical College Affiliated to Chongqing Medical University.The healthy adult Wistar rats were provided by the Experimental Animal Center of Chongqing Medical University. INTERVENTION:By blocking the bilateral common carotid arteries, bleeding on the tails and repeating ischemic reperfusion,the cerebral ischemia models of rats were established.The gastric perfusion was applied with physiological saline,danshen medical liquid or compound ferulic acid medical liquid for 5 days successively. MAIN OUTCOME MEASURES:Observation of expression and histopathology on endothelin-1(ET-1) of the cerebral tissue of rats,calcitonin gene-related peptide(CGRP),malonaldehyde, energetic metabolism and heat shock protein 70(HSP70). RESULTS:In the model group, the contents of ET-1 and malonic aldehyde were the maximum,the content of CGRP was the minimum and the energetic metabolism was disturbed.In high dosage group of compound ferulic acid, the contents of ET-1[(0.73± 0.04) ng/g] of cerebral tissue, lactic acid[(16.28± 1.1) μ mol/g]and malonic aldehyde[(116.8± 7.55) nmol/g] were remarkably reduced,and the contents of ATP[(18.22± 0.83) μ g/g] and CGRP[(1.62± 0.13) ng/g],and Na+-K+-ATP enzymatic activities [(747.82± 63.94) nkatal]were significantly increased,which indicated significant difference(P< 0.05).The quantity-effect relation was concerned to the above-mentioned functions of compound ferulic acid,for the effect in the high dosage group was superior to that in the positive control group with danshen.In compound ferulic acid treatment group, the expression of HSP70 in cerebral cortex was remarkably improved and the severity of cerebral ischemic injury reduced. CONCLUSION:Compound ferulic acid acted on the protection against cerebral ischemic reperfusion injury,the mechanism of which was related to the energetic metabolic improvement of cerebral cells,antagonistic free radical,microcirculation improvement,etc.