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

摘要:

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FK506 1 mg/kg，连续注射3 d。大鼠分别于缺氧后24 h，72 h，7 d，14 d 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72 h至 14 d 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7 d达到高峰，与HIBD组相比，在缺氧后72 h、7 d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。 ［中国当代儿科杂志，2009，11（1）：65-68］

Abstract:

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 intervention group was intraperitoneally injected with FK506 immediately after HIBD, at a dosage of 1 mg/kg daily, for three days. The HIBD group was injected with normal saline. Immunohistochemical technical was applied to examine GAP-43 expression in the hippocampus 24 and 72 hrs and 7 and 14 days after HIBD. RESULTS: Compared with the HIBD group, hematoxylin-eosin staining showed attenuated neuronal necrosis in the FK506 intervention group. In the HIBD group, the expression of GAP-43 increased significantly 72 hrs, and 7 and 14 days after HIBD compared with that in the sham-operation group. The GAP-43 expression in the FK506 intervention group was significantly higher than that in the HIBD group 72 hrs and 7 days after HIBD. CONCLUSIONS: FK506 might have neuroprotective effects against HIBD in neonatal rats.［Chin J Contemp Pediatr, 2009, 11 (1):65-68］