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坎地沙坦、阿托伐他汀及其联合应用对卒中后运动功能障碍的神经保护作用。

Neuroprotective potentials of candesartan, atorvastatin and their combination against stroke induced motor dysfunction.

机构信息

Pharmacology Division, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University, Chandigarh 160014, India.

出版信息

Inflammopharmacology. 2011 Aug;19(4):205-14. doi: 10.1007/s10787-010-0068-y.

DOI:10.1007/s10787-010-0068-y
PMID:21061073
Abstract

Cerebral ischaemia is a leading cause of death and disability. The objective of the present investigation was to explore the neuroprotective potentials of candesartan and atorvastatin alone and their combination against the cerebral ischaemia induced behavioral, biochemical, and mitochondrial dysfunction. Male Wistar rats (200-220 g) were subjected to bilateral common carotid artery occlusion for 30 min followed by 24 h reperfusion. Candesartan (0.1 and 0.3 mg/kg) and atorvastatin (10 and 20 mg/kg) were pretreated for 7 days before animals were subjected to ischaemia reperfusion injury. Various behavioral tests (locomotor activity and rotarod performance), biochemical parameters (Malondialdehyde levels, nitrite concentration, superoxide dismutase and catalase activity, redox ratio, and GST) and mitochondrial enzyme (Complex I, II, III, and IV) dysfunctions were measured in cerebral cortex, striatum and hippocampus of the ischaemic brain. Seven days candesartan (0.1 and 0.3 mg/kg) or atorvastatin (10 and 20 mg/kg) pretreatment significantly attenuated neurobehavioral alterations, oxidative damage and restored mitochondrial enzyme dysfunction as compared to control (I/R) group. Further, combined treatment of candesartan (0.1 mg/kg) and atorvastatin (10 mg/kg) significantly potentiated their protective effect which was significant as compared to their effect alone. Present study suggests the protective effect of candesartan and atorvastatin and their combination against ischaemia reperfusion induced behavioral and biochemical alterations in rats.

摘要

脑缺血是死亡和残疾的主要原因。本研究旨在探讨坎地沙坦和阿托伐他汀单独及联合应用对脑缺血诱导的行为、生化和线粒体功能障碍的神经保护作用。雄性 Wistar 大鼠(200-220g)行双侧颈总动脉结扎 30min 后再灌注 24h。坎地沙坦(0.1 和 0.3mg/kg)和阿托伐他汀(10 和 20mg/kg)预处理 7 天,然后进行缺血再灌注损伤。在缺血大脑的皮质、纹状体和海马中测量各种行为测试(运动活性和转棒性能)、生化参数(丙二醛水平、亚硝酸盐浓度、超氧化物歧化酶和过氧化氢酶活性、氧化还原比和 GST)和线粒体酶(复合物 I、II、III 和 IV)功能障碍。与对照组(I/R 组)相比,7 天坎地沙坦(0.1 和 0.3mg/kg)或阿托伐他汀(10 和 20mg/kg)预处理显著减轻神经行为改变、氧化损伤并恢复线粒体酶功能障碍。此外,坎地沙坦(0.1mg/kg)和阿托伐他汀(10mg/kg)联合治疗显著增强了它们的保护作用,与单独治疗相比具有显著性。本研究表明坎地沙坦和阿托伐他汀及其联合应用对大鼠缺血再灌注诱导的行为和生化改变具有保护作用。

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