他克莫司对缺氧缺血性脑损伤新生大鼠海马GAP-43表达的影响

Effect of tacrolimus on growth-associated protein-43 expression in the hippocampus of neonatal rats with hypoxic-ischemic brain damage

目的新生儿缺氧缺血性脑损伤(HIBD)是新生儿期常见病,具有较高的致死率和神经系统致残率,目前尚无有效干预措施。新型的免疫抑制剂他克莫司(FK506)已在成年动物缺血性脑损伤模型中显示神经保护作用,目前尚无新生动物模型研究。该研究旨在探讨FK506对缺氧缺血性脑损伤新生大鼠海马生长相关蛋白(GAP-43)表达的影响。方法7日龄Sprague-Dawley大鼠随机分为假手术组、HIBD组和FK506干预组,HIBD组和干预组制备HIBD模型,干预组缺氧后即刻腹腔内注射FK5061mg/kg,连续注射3d。大鼠分别于缺氧后24h,72h,7d,14d断头取脑,切片行苏木精-伊红染色及免疫组化Envision法检测海马GAP-43的表达。结果同HIBD组相比,干预组神经细胞灶性坏死减少。HIBD组海马GAP-43的表达较假手术组增加,在缺氧后72h至14d差异有显著性意义(P<0.05)。干预组海马GAP-43的表达在缺氧后7d达到高峰,与HIBD组相比,在缺氧后72h、7d表达增加,差异有显著性(P<0.05)。结论FK506可能对HIBD新生大鼠具有神经保护作用。

Objective Immunosuppressant tacrolimus (FK506) has shown neuroprotective effects on hypoxic-ischemic brain damage (HIBD) in the adult animal model. This study investigated whether FK506 has a protection against HIBD in neonatal rats by examining growth-associated protein-43 (GAP-43) expression in the hippocampus.Methods Ninety-six seven-day-old Sprague-Dawley rats were randomly divided into three groups: sham-operation, HIBD and FK506 intervention group. HIBD was induced in the later two groups. The FK506 i...