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马赛替尼通过抑制自噬和细胞凋亡减轻脑缺血/再灌注损伤

王燕, 平锋锋, 周丹丽, 陈艳华, 凌菁菁

王燕, 平锋锋, 周丹丽, 陈艳华, 凌菁菁. 马赛替尼通过抑制自噬和细胞凋亡减轻脑缺血/再灌注损伤[J]. 中国药科大学学报, 2021, 52(2): 227-235. DOI: 10.11665/j.issn.1000-5048.20210212
引用本文: 王燕, 平锋锋, 周丹丽, 陈艳华, 凌菁菁. 马赛替尼通过抑制自噬和细胞凋亡减轻脑缺血/再灌注损伤[J]. 中国药科大学学报, 2021, 52(2): 227-235. DOI: 10.11665/j.issn.1000-5048.20210212
WANG Yan, PING Fengfeng, ZHOU Danli, CHEN Yanhua, LING Jingjing. Masitinib alleviated cerebral ischemia/reperfusion injury by inhibiting autophagy and apoptosis[J]. Journal of China Pharmaceutical University, 2021, 52(2): 227-235. DOI: 10.11665/j.issn.1000-5048.20210212
Citation: WANG Yan, PING Fengfeng, ZHOU Danli, CHEN Yanhua, LING Jingjing. Masitinib alleviated cerebral ischemia/reperfusion injury by inhibiting autophagy and apoptosis[J]. Journal of China Pharmaceutical University, 2021, 52(2): 227-235. DOI: 10.11665/j.issn.1000-5048.20210212

马赛替尼通过抑制自噬和细胞凋亡减轻脑缺血/再灌注损伤

基金项目: 无锡市卫生健康委科研资助项目(No.Q202010);江苏省六大人才高峰资助项目(No.YY-128);无锡市太湖人才计划高层次人才培养资助项目(No.BJ2020088,BJ2020001)

Masitinib alleviated cerebral ischemia/reperfusion injury by inhibiting autophagy and apoptosis

Funds: This study was supported by the Scientific Research Project of Wuxi Health Commission (No.Q202010); the Six Talent Peak Project of Jiangsu Province (No.YY-128) and Wuxi Taihu Talent Plan Top Talents Project (No.BJ2020088, No.BJ2020001)
  • 摘要: 观察马赛替尼对大鼠脑缺血/再灌注损伤的保护作用并探讨其机制。雄性SD大鼠随机分成假手术组、模型组、马赛替尼低、中、高剂量治疗组,每组12只。线栓法制备大鼠大脑中动脉梗阻2 h后复灌模型,即刻给药,每天给药两次,连续7 d。再灌注7 d后行神经功能症状缺损评分,检测脑梗死体积及脑含水量,Western blot和PCR检测损伤周围脑组织自噬和凋亡相关蛋白和基因的表达。术后7 d,与模型组相比,各给药组大鼠神经功能缺损评分、脑梗死体积和脑积水均明显降低。模型组大鼠脑组织中明显上升,p62的表达明显下降。马赛替尼各组均能不同程度地下调LC3II/I、Beclin-1、Bax等凋亡蛋白和NF-κB的表达,上调p62的表达。马赛替尼发挥神经保护作用的机制之一可能与抑制自噬和细胞凋亡通路有关。
    Abstract: To investigate the neuroprotective effect and possible mechanism of masitinib on cerebral ischemia-reperfusion injury in rats, healthy adult male Sprague-Dawley rats were divided into sham group (n = 12), model group (n = 12), masitinib low dosage group (n = 12), masitinib middle dosage group (n = 12), and masitinib high dosage group (n = 12). All rats was subjected to middle cerebral artery occlusion (MCAO) for two hours and reperfusion except sham group, and received treatment twice per day for 7 days once reperfusion started.Neurological score, infarct volume, and brain water content were detected; some autophagic markers, apoptotic and inflammatory cytokines were evaluated by Western blot and PCR after 7 d of reperfusion. Treatment with masitinib significantly ameliorated neurologic deficit, infarct volume and brain water after I/R injury. Masitinib also decreased the ratio of LC3II/I and the expression of Beclin-1 and increased the expression of p62 in the brain tissues of rats with I/R injury.Furthermore, it could inhibit apoptosis-related proteins and NF-κB expression. Masitinib could relieve the cerebral ischemia-reperfusion injury in rats through inhibiting autophagy and apoptosis.
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出版历程
  • 收稿日期:  2020-09-25
  • 修回日期:  2021-03-24
  • 刊出日期:  2021-04-24

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