牡荆苷对脑缺血再灌注大鼠脑损伤保护作用及其机制研究

目的：本研究旨在探讨牡荆苷对脑缺血再灌注大鼠脑损伤的保护作用及其作用机制。方法：采用Longa 改良线栓法建立大鼠大脑中动脉阻塞（middle cerebral artery occlusion，MCAO）模型。实验随机分为假手术组，模型组，模型+ 依达拉奉阳性对照组（3.24 μmol·kg-1），模型+ 牡荆苷（1.62、3.24、6.48 μmol·kg-1）不同剂量组，大鼠缺血2 h 再灌注1 h 后腹腔注射给药，连续给药时间为1 d 和3 d。2，3，5- 氯化三苯基四氮唑（triphenyltetrazolium chloride，TTC）测大鼠脑梗死体积，干湿重法测脑组织含水量，相应试剂盒法检测超氧化物歧化酶（superoxide dismutase，SOD）活性、活性氧（reactive oxygen species，ROS）和丙二醛（methane dicarboxylic aldehyde，MDA）含量，免疫组化检测水孔通道蛋白4（aquaporin 4，AQP-4）阳性细胞表达，RTqPCR检测Toll 样受体4 （Toll-like receptor 4，TLR4）和核因子κB（nuclear factor κB，NF-κB）mRNA 表达水平，ELISA 测定肿瘤坏死因子α（tumor necrosis factor α，TNF-α）含量，HE 染色观察大鼠神经细胞的形态。结果：与假手术组相比，模型组大鼠再灌注后缺血侧脑组织出现明显的梗死灶，含水量明显增多，SOD 活性明显降低，ROS 和MDA 含量明显升高；与模型组相比，给药组大鼠脑组织含水量降低，抗氧化酶活性升高，抗炎作用显著，显著改善脑缺血再灌注大鼠细胞病理形态，在一定剂量范围内，呈剂量依赖性；与依达拉奉对照组相比，牡荆苷中、低剂量组作用较弱（P<0.01，P<0.05）；牡荆苷高剂量组与依达拉奉作用相当，差异无显著性。结论：牡荆苷对脑缺血再灌注大鼠脑损伤的保护作用可能是通过抗氧化应激和抗炎作用实现。

Protective Effect of Vitexin on Cerebral Ischemia-Reperfusion Injury in Rats

Objective：This study investigated the possible mechanism of vitexin in cerebral ischemia-reperfusion （CIR） model rats. Methods：Middle cerebral artery occlusion （MCAO） model was established in this study. This experiment was randomly divided into sham group，model group，model+edaravone group （3.24 μmol·kg-1），and different concentrations of vitexin groups （1.62，3.24，6.48 μmol·kg-1）. After 1 h of reperfusion，the rats were intraperitoneally injected for one and three days. Triphenyltetrazolium chloride （TTC） was used to measure brain infarct volume of rats，the water content of brain tissue was measured throughwet-dry weighting method，methane dicarboxylic aldehyde （MDA） content，superoxide dismutase （SOD） activity and reactive oxygen species （ROS） were determined by kit methods，the positive cells of aquaporin-4 （AQP-4） were detected by immunohistochemistry，the mRNA levels of Tolllike receptor 4 （TLR4） and nuclear factor κB （NF-κB） mRNA were detected by RT-qPCR，tumor necrosis factor α（ TNF-α） content was measured by ELISA，the cell morphology of rats was observed by HE staining. Results：Compared to the sham group，model group showed significant
infarcts and increased brain water content. Compared to model group，vitexin decreased cerebral infarct volume and brain water content，increased SOD activity，and reduced the expressions of inflammatory factors significantly，improved cell morphology and the effects were dose dependent. Moreover，the protective effect of vitexin after 3 d treatment was better than that after 1 d. Compared to edaravone group，the effects of vitexin groups （1.62，3.24 μmol·kg-1） were lower （P<0.05，P<0.01），but showed similar effect of vitexin group at concentration of 6.48 μmol·kg-1. Conclusion：Vitexin could protect CIR injury through attenuating oxidative stress and inhibiting the inflammatory response.