Liu X, Zhang X, Zhang J, Kang N, Zhang N, Wang H, Xue J, Yu J, Yang Y, Cui H, Cui L, Wang L, Wang X
Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China.
Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China; Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang, Hebei 050000, PR China; Hebei Key Laboratory for Neurology, Shijiazhuang, Hebei 050000, PR China.
Neuroscience. 2014 May 30;268:318-27. doi: 10.1016/j.neuroscience.2014.03.032. Epub 2014 Mar 26.
Apoptosis is a major form of cell death in cerebral ischemia/reperfusion (I/R) pathogenesis and may represent a target for treatment. Diosmin (DM), a micronized purified flavonoid drug, possesses an anti-apoptotic effect in the treatment of varicose veins and renal injury. However, the effect of DM in the acute phase of cerebral I/R is not clear. This study investigated DM's role in cerebral I/R and its potential mechanism.
Male CD-1 mice were subjected to transient middle cerebral artery occlusion (tMCAO). Experiment 1 was used to evaluate the time course expression of Janus tyrosine kinase-2 (JAK2), signal transducer and activator of transcription-3 (STAT3), phosphorylated JAK2 (pJAK2) and phosphorylated STAT3 (pSTAT3) after cerebral I/R, and six time points were included. In experiment 2, DM was given orally at doses of 50mg/kg or 100mg/kg for 6 consecutive days before receiving tMCAO. At 24h after reperfusion, neurological deficit, Nissl staining, brain water content and infarct volume were examined. Bcl-2, Bax, pJAK2, and pSTAT3 were detected by immunohistochemistry, qRT-PCR and Western blot. Confocal microscope was used to observe the location of pSTAT3 in the cerebral cortex.
Compared with Vehicle group, the high dose of DM significantly alleviated neurological deficit, brain water content, infarct volume, increased the Nissl-positive cells, upregulated the expression of pJAK2, pSTAT3 and Bcl-2 and downregulated Bax (P<0.05).
These results showed that DM protected against cerebral I/R injury through activating JAK2/STAT3 signal pathway.
细胞凋亡是脑缺血/再灌注（I/R）发病机制中细胞死亡的主要形式，可能是治疗的靶点。地奥司明（DM）是一种微粉化纯化的黄酮类药物，在治疗静脉曲张和肾损伤方面具有抗凋亡作用。然而，DM在脑I/R急性期的作用尚不清楚。本研究探讨了DM在脑I/R中的作用及其潜在机制。
雄性CD-1小鼠接受短暂性大脑中动脉闭塞（tMCAO）。实验1用于评估脑I/R后Janus酪氨酸激酶2（JAK2）、信号转导和转录激活因子3（STAT3）、磷酸化JAK2（pJAK2）和磷酸化STAT3（pSTAT3）的时间进程表达，共包括6个时间点。在实验2中，在接受tMCAO前连续6天口服给予DM，剂量为50mg/kg或100mg/kg。再灌注24小时后，检测神经功能缺损、尼氏染色、脑含水量和梗死体积。通过免疫组织化学、qRT-PCR和蛋白质印迹法检测Bcl-2、Bax、pJAK2和pSTAT3。使用共聚焦显微镜观察pSTAT3在大脑皮质中的定位。
与溶剂对照组相比，高剂量DM显著减轻神经功能缺损、脑含水量、梗死体积，增加尼氏阳性细胞，上调pJAK2、pSTAT3和Bcl-2的表达，下调Bax（P<0.05）。
这些结果表明，DM通过激活JAK2/STAT3信号通路保护脑I/R损伤。
