摘要
目的探讨银杏内酯A(Ginkgolide A,GA)对缺血/再灌注脑损伤小鼠的保护作用及其可能的作用机制。方法采用小鼠短暂性大脑中动脉阻塞(transient middle cerebralartery occlusion,tMCAO)模型观察GA(10,20 and 40 mg.kg-1)对小鼠脑梗死范围、脑含水量及神经症状的影响,并进行病理组织学检查;采用实时荧光定量PCR技术检测缺血大脑皮层p53 mRNA的表达;应用Western blot法检测缺血大脑皮层IκBα、pIκBα及Caspase-3蛋白水平的表达。结果 GA对缺血/再灌注小鼠神经症状有明显的改善作用,能明显降低脑梗死范围,降低脑含水量,脑组织病理组织学也显示了GA对神经细胞的保护作用。Western blot结果显示:小鼠脑缺血/再灌后,IκBα蛋白水平明显降低,GA能明显升高IκBα的蛋白水平,降低pIκBα和Caspase-3的蛋白水平。PCR结果表明:小鼠脑缺血/再灌后,p53 mRNA水平升高,GA能下调p53 mRNA的表达。结论 GA对缺血/再灌注小鼠脑损伤有明显保护作用,该作用可能与其抑制NF-κB信号通路,下调p53、Caspase-3的表达有关。
Aim To observe the protective effects of Ginkgolide A （GA） on cerebral ischemia-reperfusion injury in mice and explore its mechanism. Methods Cerebral ischemia-reperfusion injury in mice was induced by middle cerebral artery occlusion. The neurological outcome,infarct size and water contents were evaluated. The pathomorphology examination was done. Western blot analysis was employed to determine alterations in protein levels of IKBα, pIKBα and Caspase- 3. Quantitative Real-Time RT-PCR was used to detect induction of NF-kB target gene p53 mRNA. Results GA （40,20 mg·kg-1 ） markedly improved neurologic deficits, and decreased infarct volume and edema at 24 h after reperfusion in mice. The pathological slices also proved its protective effects on neuron cells. Western blot analysis indicated a significant decrease in IKBα levels after ischemia. GA markedly up-regulated the protein levels of IKBα, and down-regulated the protein levels of pIKBα and Caspase-3. GA also repressed the ischemia-induced increase in expression of NF-KB target gene p53 mRNA. Conclusion GA has protective effects on cerebral ischemia-reperfusion injury in mice. Which is probably related to inhibition of NF-KB signaling pathway and down-regulation of the levels of p53 and Caspase-3.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2012年第8期1105-1110,共6页
Chinese Pharmacological Bulletin
基金
国家自然科学基金青年基金资助项目(No 81000496)
