依达拉奉对脓毒性休克大鼠心肌细胞损伤作用.docVIP

依达拉奉对脓毒性休克大鼠心肌细胞损伤作用 　 作者：霍小萍，顾学兰，刘良明，刁有芳，马春艳，陈家慧，李萍，卢是 【关键词】 依达拉奉；氧自由基；休克,脓毒性；心肌损伤 【Abstract】 AIM: To investigate the effect of edaravone(ED), a novel free radical scavenger, on cardiac function and myocardial cell injury in rats with septic shock. METHODS: After treatment with three different doses (6.0, 3.0 and 1.5 mg/kg) of ED to rats 1 h after septic shock, changes of MAP, LVESP, LVEDP,±dp/dtmax were determined in 4 different time phases. The activities of SOD, CAT, LDH and the concentrations of MDA, LD in myocardial tissue were measured. The pathologic change of myocardial tissue was observed by HE staining. RESULTS: Compared with septic shock group, MAP,LVESP and +dp/dtmax were increased remarkably in ED treatment groups. The activities of SOD and CAT and the concentration of MDA in ED groups were close to those in normal control group. Histological examination showed congestion, edema and inflammatory cell infiltration in myocardial tissue, while ED treatment attenuated the above pathological changes of myocardium. CONCLUSION: ED has a satisfying therapeutic effect on cardiac dysfunction in rats with septic shock, which may be related to attenuating myocardial injury. 【Keywords】 edaravone; Oxygen free radicals; shock, septic; Myocardial injury 【摘要】 目的： 观察氧自由基清除剂依达拉奉（edaravone, ED）对脓毒性休克大鼠心脏功能和心肌损伤的作用. 方法： 在大鼠脓毒性休克后1 h用3个剂量ED (6.0, 3.0和1.5 mg/kg)治疗，测定休克后4个时相点平均血压（MAP）、左室收缩末期压力（LVESP）、左室舒张末期压力（LVEDP）、左室压力上升及下降最大变化速率（±dp/dtmax）等心功能指标；取心肌组织测超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、乳酸脱氢酶（LDH）活性和乳酸（LD）、丙二醛（MDA）含量，并观察形态学改变. 结果： 与脓毒性休克组比较，ED可显著升高MAP，LVESP和±dp/dtmax，并使SOD，CAT活性增强以及MDA浓度降低接近对照组；组织学观察可见模型组心肌充血、水肿及炎性细胞浸润等，ED可明显改善以上形态学变化. 结论： ED具有抗脓毒性休克心功能不全的作用，其机制与减轻心肌损伤有关. 【关键词】 依达拉奉；氧自由基；休克，脓毒性；心肌损伤 心功能不全和心肌细胞损伤是脓毒性休克的主要致命性并发症，有40%的脓毒症患者出现左、右心功能不全［1-2］. 脓毒症时菌体膜产生的内毒素（lipopolysaccharide, LPS）入血可直接或间接通过细胞因子和自由基的作用引起心肌损伤和心功能不全［3］,实验证实抗氧化剂谷胱甘肽加N乙酰半胱氨酸可明显减少脓毒症休克患者血液中活性氧浓度，改善心功能指数［4］. 依达拉奉［edaravone, ED, 3甲基1苯基2吡唑啉5酮（MCI186）］是新型强效的自由基清除剂，是临床治疗缺血性脑卒中的有效药物［5］. 我们通过观察ED对脓毒性休克大鼠心功能、心肌氧自由基和