新型依达拉奉丹参素共轭物对大鼠局灶性脑缺血再灌注损伤的保护作用及其机制

Protective effect of novel edaravone and danshensu conjugate on focal cerebral ischemia-reperfusion injury in rats and its underlying mechanism

目的:观察依达拉奉丹参素共轭物(IM-009)对大鼠局灶性缺血再灌注损伤模型的保护作用,对其作用机制进行初步研究。方法:将SD大鼠随机分为假手术组、模型组、依达拉奉治疗组、IM-009低剂量治疗组以及IM-009高剂量治疗组。采用线栓法制作大鼠局灶性脑缺血再灌注损伤模型,药物干预后,观察各组动物的脑梗死体积及其脑水肿程度。用试剂盒检测脑组织中丙二醛(MDA)的含量和超氧化物歧化酶(SOD)的活力。采用体外非细胞实验法检测IM-009对羟自由基(.OH)和超氧阴离子(.O2-)的清除能力。结果:1)与模型组比较,IM-009治疗组大鼠的脑梗死体积明显减小,脑水含量降低,并且IM-009高剂量组大鼠的脑梗死体积小于依达拉奉治疗组(均P<0.05)。2)与模型组比较,IM-009治疗组大鼠的MDA含量显著降低,SOD活性明显提高(均P<0.05)。3)IM-009对.OH和.O2-具有较强的清除能力(均P<0.05)。结论:IM-009对大鼠局灶性脑缺血再灌注损伤动物模型具有保护作用,其作用机制可能与其清除自由基有关。

Objective: To investigate the protective effect of edaravone and danshensu conjugate(IM-009) on focal cerebral ischemia-reperfusion injury in rats and its underlying mechanisms. Methods: Rats were randomly assigned into 6 groups, including a sham group, a model group, an edaravone-treated group, a danshensu-treated group, a low dose of IM-009-treated group and a high dose of IM-009-treated group. The focal cerebral ischemia-reperfusion model was established by intraluminal filament. Aft er the drug treatment, the infarct volume and extent of brain edema were measured. The levels of MDA and SOD were determined by the corresponding assay kit. The scavenging effect of IM-009 on hydroxyl radical and superoxide anion was also measured in a cell free system. Results: 1) In comparison with the model group, the infarct volume and water content in rat brain after IM-009 treatment were significantly reduced. The protective effect of IM-009 at higher dose was much stronger than that of edaravone or danshensu(all P<0.05). 2) IM-009 significantly reduced the levels of MDA and increased the activity of SOD(all P<0.05). 3) IM-009 demonstrated strong activities in scavenging.OH and.O2-(all P<0.05). Conclusion: IM-009 is able to protect rats from ischemia-reperfusion injury. The protective effect of IM-009 could be due to its radical-scavenging action.