西维来司钠减轻大鼠脑缺血/再灌注损伤

Sivelestat sodium reduces cerebral ischemia-reperfusion injury in rats

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。

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 try 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.