克拉维酸通过下调炎症因子表达对抗缺血损伤发挥神经保护作用

目的：探讨克拉维酸对抗大鼠脑缺血的作用及其机制。方法：实验分8组：空白对照组，假手术组，溶剂对照组，克拉维酸对照组，全脑缺血-再灌注损伤组，以及克拉维酸低、中、高剂量保护组。采用四血管闭塞法建立动物全脑缺血模型；术后3 d通过硫堇尼氏体染色观察海马CA1区细胞形态；术后1 d通过RT-PCR及ELISA分析海马组织TNF-α、IL-1β及IL-6 mRNA及蛋白含量。结果：克拉维酸可减少全脑缺血引起的大鼠海马CA1区锥体神经元迟发性神经元死亡，可降低缺血组织中炎症因子TNF-α、IL-1β及IL-6 mRNA及蛋白表达水平。结论：克拉维酸可对抗脑缺血，发挥神经保护作用，其保护作用与抑制炎症因子表达有关。

Neuroprotective effects of clavulanic acid against cerebral ischemia partly through down-regulating expression of inflammatory factors

OBJECTIVE To investigate protective effects of clavulanic acid against cerebral ischemia in rats and the mechanism.METHODS Male SD rats (210-230 g) used in this study were divided randomly into eight groups:control group (con),sham group (sham),vehicle-control group (v-con),clavulanic acid-control group (CA-con),cerebral ischemia group (injury),clavulanic acid protection group 1 mg·kg^-1 (CA-_L),clavulanic acid protection group 5 mg·kg^-1 (CA-_M),and clavulanic acid protection group 10 mg·kg^-1 (CA-_H).Neuropathological evaluation under thionin stain was performed 3 d after sham operation or cerebral ischemia.The mRNA expression and protein production of TNF-α,IL-1β and IL-6 in CA1 hippocampus were investigated by RT-PCR and ELISA 1 d after sham operation or cerebral ischemia.RESULTS Clavulanic acid reduced delayed death of pyramidal neurons in CA1 hippocampus induced by global cerebral ischemia.Clavulanic acid attenuated ischemia induced upregulation of TNF-α,IL-1β and IL-6.CONCLUSION Clavulanic acid can protect pyramidal neurons against global cerebral ischemia partly through down regulating expression of inflammatory factors.