雷公藤甲素对大鼠脑缺血再灌注损伤的影响及机制研究
投稿时间:2023-11-10  修订日期:2023-12-29  点此下载全文
引用本文:
摘要点击次数: 424
全文下载次数: 0
作者单位邮编
竺东杰 中国人民解放军联勤保障部队第九〇六医院 315100
中文摘要:目的 探讨雷公藤甲素对大鼠脑缺血再灌注损伤(CIRI)的影响并初探其分子机制。方法 将144只Wistar大鼠随机分为假手术组、模型组、雷公藤甲素低、中、高剂量组和丁苯酞组,每组24只。通过阻断大脑中动脉2 h构建CIRI大鼠模型,各组均于造模前3天开始1次/天ip给药。再灌注24 h后,行神经功能缺失评分,TTC染色法检测脑梗死率; EB渗透实验检测血脑屏障(BBB)通透性; HE 、TUNEL染色观察缺血半暗带皮层神经元病理学改变;ELISA法检测缺血侧大脑皮层炎症因子含量,Western blot法检测TLR4/NF-κB通路相关蛋白表达。结果 与模型组比较,雷公藤甲素中、高剂量组和丁苯酞组神经功能缺失评分、脑梗死率、EB含量显著降低(P<0.05);缺血半暗带皮层神经元病理学改变明显改善,凋亡率显著降低(P<0.05);炎症因子TNF-α、IL-1β含量和TLR4、p-NF-κB、cleaved Caspase-3、Bax相对表达量显著降低,Bcl-2相对表达量显著升高,p-NF-κB/NF-κB和Bax/Bcl-2比值显著降低(P<0.05)。雷公藤甲素高剂量组对各检测指标的调控作用优于丁苯酞组(P<0.05)。结论 雷公藤甲素能够保护BBB通透性,减轻CIRI大鼠神经功能缺失和神经元病变,降低脑梗死率,作用机制可能与抑制TLR4/NF-κB通路及其介导的炎症反应和神经元凋亡有关。
中文关键词:雷公藤甲素  脑缺血再灌注  TLR4/NF-κB通路  炎症  凋亡
 
Effects of Triptolide on cerebral ischemia-reperfusion injury in rats and its mechanism
Abstract:Objective To investigate the effect of Triptolide on cerebral ischemia- reperfusion injury (CIRI) and explore its molecular mechanism. Methods One hundred and forty-four Wistar rats were randomly divided into sham operation group, model group, low, medium and high dose of triptolide group and butylphthalide group, with 24 rats in each group. The CIRI rat model was established by blocking the middle cerebral artery for 2 hours. 3 days before modeling, the rats in each group were ip administration once a day. 24 hours after reperfusion, the neurological deficit score was detected, the rate of cerebral infarction were measured by TTC staining, the blood brain barrier (BBB) permeability was detected by EB penetration test. The pathological changes neurons in the ischemic penumbra cortex were observed by HE staining and TUNEL staining. The content of inflammatory factors in ischemic cerebral cortex were detected by ELISA method. The expression of TLR4/NF-κB pathway related proteins were detected by Western blot. Results Compared with the model group, the neurological deficit score, cerebral infarction rate and EB content in the Triptolide middle, high dose groups and the Butylphthalide group were significantly decreased (P<0.05). The pathological changes of cortical neurons in the ischemic penumbra were significantly improved, and the apoptosis rate of neurons was significantly decreased (P<0.05). The content of TNF-α, IL-1β and the expression of TLR4, p-NF-κB, cleaved Caspase-3, Bax were significantly decreased, the expression of Bcl-2 was significantly increased, the ratio of p-NF-κB/NF-κB and Bax/Bcl-2 were significantly decreased (P<0.05). The regulatory effect of the high-dose triptolide group on various detection indexes were better than that of the Butylphthalide group (P<0.05). Conclusion Triptolide can protect the permeability of BBB, improve the neurological deficit and neuropathy in CIRI rats, and reduce the rate of cerebral infarction, its mechanism may be related to the inhibition of TLR4/NF-κB pathway and which mediated inflammatory response and neuronal apoptosis.
keywords:Triptolide  Cerebral ischemia-reperfusion  TLR4/NF-κB pathway  Inflammation  Apoptosis
  查看/发表评论  下载PDF阅读器
关闭

分享按钮