西维来司钠减轻大鼠脑缺血/再灌注损伤

目的： 探讨中性粒细胞弹性蛋白酶(NE)抑制剂-西维来司钠（ONO-5046）对大鼠全脑缺血/再灌注(CI/R)损伤的作用及其机制。方法: 采用夹闭双侧颈总动脉合并低血压法建立大鼠CI/R模型，缺血20 min，再灌注24 h。于再灌注时经股静脉输注不同剂量ONO-5046（3、10、30 mg·kg-1·d-1）。分光光度法测定丙二醛(MDA)含量及超氧化物歧化酶(SOD)、髓过氧化物酶(MPO)活性；免疫组化法测定大鼠核转录因子-κB(NF-κB)和肿瘤坏死因子-α(TNF-α)表达；Western blotting及ELlSA法分别测定脑组织NF-κB p65及TNF-α含量。结果: ONO-5046组脑组织MDA含量较模型组降低，SOD活性升高，MPO活性降低； 脑皮质NF-κB、TNF-α阳性表达细胞数及NF-κB p65、TNF-α含量都明显少于模型组。结论: ONO-5046可减轻大鼠CI/R后脂质过氧化和炎症反应，这可能是其发挥脑保护作用的机制。

Sivelestat sodium reduces cerebral ischemia-reperfusion injury in rats

AIM: To investigate the protective effect of neutrophil elastase inhibitor sivelestat sodium hydrate (ONO-5046) on the global brain ischemia-reperfusion injury in rats.METHODS: The global brain ischemia model in rats was induced by occlusion both sides of arteria carotis communis with hypotension for 20 min, followed by 24 h reperfusion. The brain water ratio was detected. The levels of malondialdehyde (MDA), the activities of superoxide dismutase (SOD) and myeloperoxidase (MPO) in brain were measured by spectrophotometer. Immunohistochemistry was employed to assess the expression of nuclear factor κB (NF-κB) and tumor necrosis factor α (TNF-α). The histopathological change was observed with HE staining. RESULTS: Pretreatment with ONO-5046 markedly reduced brain water ratio by global brain ischemia, decreased MDA levels, increased SOD activity, inhibited MPO activity and decreased expression of NF-κB and TNF-α. ONO-5046 also improved the brain from histopathological injury. CONCLUSION: NE inhibitor ONO-5046 has a protective effect on global brain ischemia-reperfusion injury and NE provides a new target for treatment of cerebral ischemia-reperfusion injury.