阿伦狄克酸对脑缺血再灌注损伤食蟹猴模型的神经保护作用  

Neuroprotective effect of arundic acid on Cynomolgus macaques with cerebral ischemia-reperfusion injury

作　　者：王向伟 周永馨 庄永杰 陈继巧 毛佳静 周静 邓志豪 邢柳柳 周业明 付立杰 WANG Xiangwei;ZHOU Yongxin;EIKETSU Sho;CHEN Jiqiao;MAO Jiajing;ZHOU Jing;DENG Zhihao;XING Liuliu;ZHOU Yeming;FU Lijie(Breakthrough Pharmaceuticals(Nantong)Inc.,Nantong 226133,China)

机构地区：[1]布瑞迅药业(南通)有限公司,江苏南通226133

出　　处：《中国药理学与毒理学杂志》2024年第4期241-248,共8页Chinese Journal of Pharmacology and Toxicology

摘　　要：目的评价阿伦狄克酸对食蟹猴脑缺血再灌注损伤(CIRI)的治疗作用。方法9只健康雄性食蟹猴,通过阻断左侧大脑中动脉4 h后再灌注建立CIRI模型。脑梗死72 h后,随机分为模型〔20%(W∶V)Solutol HS15和10%(V∶V)PEG400〕、模型+阿伦狄克酸钙10和30 mg·kg^(-1)组,每组3只,口服给药,每天2次,连续28 d。治疗期间,通过一系列神经行为学检查,如上肢采食技能测试和笼旁行为观察,及大脑梗死体积和脑水肿体积磁共振数据评估神经损伤和恢复。结果模型组食蟹猴在CIRI后表现出自然自发性恢复。与模型组相比,模型+阿伦狄克酸钙30 mg·kg^(-1)组行为学、上肢活动和脑病变体积明显恢复(P<0.05),模型+阿伦狄克酸钙10 mg·kg^(-1)组无明显改善。结论阿伦狄克酸可缩小CIRI食蟹猴模型脑梗死面积,改善神经行为活动和骨骼肌协调功能。OBJECTIVE To evaluate the therapeutic effect of arundic acid against cerebral ischemia-reperfusion injury(CIRI)Cynomolgus macaques.METHODS Nine healthy male cynomolgus monkeys were subjected to 4 h ligation of the left middle cerebral artery followed by reperfusion before they were randomly divided into model,model+calcium arundate 10 and 30 mg·kg^(-1) groups,with three cynomolgus monkeys in each.72 h post-cerebral infarction,the three groups were orally administrated with viehcles[20%(W:V)Solutol HS15 and 10%(V:V)PEG 400]or calcium arundate 10 and 30 mg·kg^(-1) twice daily for 28 consecutive days,respectively.Neurological impairment and recovery were assessed by a series of neurobehavioral tests,such as upper extremity feeding skill tests and observation of animal cage behaviour,as well as magnetic resonance data of cerebral infarction volume and cerebral edema volume during treatment.RESULTS The model group showed natural spontaneous recovery after the middle cerebral artery occlusion.After treatment with calcium arundate 30 mg·kg^(-1) twice daily,a remarkable neurological function recovery in terms of behavior,upper limb activity,and brain lesion volume was observed(P<0.05).Meanwhile,calcium arundate 10 mg·kg^(-1) group did not show convincing improve⁃ment in comparison with the model group.CONCLUSION Arundic acid can reduce the volume of the infarct area,improve neurobehavioral activities,and skeletal muscle coordination function in the Cyno⁃molgus macaques model of CIRI.Arundic acid has the potential to be an effective neuroprotective agent in cerebral ischemia stroke.

关 键 词：阿伦狄克酸 脑缺血再灌注损伤 神经行为学 食蟹猴 

分 类 号：R971[医药卫生—药品] R965[医药卫生—药学]