碱性成纤维细胞生长因子对新生大鼠缺氧缺血性脑损伤的保护作用

Effects of Basic Fibroblast Growth Factor on the Recovery of Neurons Following Hypoxic-Ischemic Brain Damage in Neonatal Rats

摘要:

目的   探讨碱性成纤维细胞生长因子（ ｂＦＧＦ）对新生大鼠缺氧缺血性脑损伤( ＨＩＢＤ）的保护作用。方法  将 ３２只 ７日龄Ｗｉｓｔａｒ大鼠分为４组：假手术组、ＨＩＢＤ组、 ｂＦＧＦ治疗组（分大剂量组１７．５ μｇ／ｋｇ和小剂量组１０ μｇ／ｋｇ），每组 ８只。后３组动物制成 ＨＩＢＤ模型，给予治疗组大鼠连续 ７ ｄ腹腔注射 ｂＦＧＦ， ＨＩＢＤ组腹腔注射等体积生理盐水作为对照。全部大鼠于术后１４ ｄ处死，对脑纹状体、皮质的光镜下结构、乙酰胆碱酯酶（ＡｃｈＥ）、酸性磷酸酶（ＡＣＰ）活性变化进行观察和比较。结果  新生大鼠 ＨＩＢＤ后皮质、纹状体有选择性神经元坏死及胶质细胞增生， ｂＦＧＦ治疗组上述病变明显减轻； ＨＩＢＤ后纹状体、皮质神经元 ＡｃｈＥ活性明显下降(－～＋）， ｂＦＧＦ组 ＡｃｈＥ活性（＋～＋＋）较ＨＩＢＤ组恢复快； ＨＩＢＤ后纹状体神经元 ＡＣＰ活性明显增高（＋＋＋）， ｂＦＧＦ组 ＡＣＰ活性（＋＋）变化程度小于ＨＩＢＤ组。但大、小剂量ｂＦＧＦ治疗组未见明显差异。结论  ｂＦＧＦ能通过影响受损神经元的酶物质代谢而加快ＨＩＢＤ新生大鼠神经元的修复。

Abstract:

OBJECTIVE: To investigate the effects of basic fibroblast growth factor(bFGF) on neurons following hypoxic-ischemic brain damage(HIBD) in neonatal rats. METHODS: Seven-day-old Wistar rats were randomly assigned into a sham operation group, an HIBD group, and 2 bFGF-treated(10 μg/kg and 17.5 μg/k g) HIBD groups(n=8 for each group). The HIBD model using the carotid ligation were previously established. In the bFGF groups, the rats received bFGF by intrapritoneal injection for 7 days. The rats in the untreated HIBD group were injected with normal saline(NS) intraperitoneally at the same time as the bFGF groups. Micro-morphological features and activities of acetylcholinesterase(AchE) and acid phosphatase(ACP) in the HIBD rats treated with bFGF were compared with those in the untreated HIBD rats. RESULTS: Two weeks after HI, the brain ipsilateral to the carotid ligation was severely injured, having selective neuronal cell death, gliosis in the striatum and cortex of the untreated HIBD group; these findings were reduced in the bFGF-treated groups. AchE activity in the damaged neurons of the striatum and cortex obviously decreased in the HIBD group, but was nevertheless higher in the bFGF-treated groups than in the untreated animals. ACP activity in the injured neurons of the ipsilater al striatum increased markedly, but the increase in ACP activity was less in the bFGF groups than in the untreated HIBD group. There were no significant differences in the outcome between the two bFGF dosages.CONCLUSIONS: bFGF may promote the recovery of enzyme activities and the micro-morphological structure of neurons in the striatum and cortex following HI.