神经生长因子减轻新生大鼠缺氧缺血性脑损伤的研究

目的：探讨神经生长因子(NGF)减轻新生大鼠缺氧缺血性脑损伤(HIBD)的作用及其机制。方法：将NGF以0.1 μg/kg和0.3 μg/kg两个剂量组用于新生大鼠HIBD模型，采用干湿比重法、原子吸收光谱法和高效液相色谱电化学法检测缺氧缺血后脑组织含水量、脑组织钙含量和单胺类神经递质含量变化。结果：新生大鼠缺氧缺血组结扎侧脑组织平均含水量、组织钙含量及单胺类神经递质(除DOPAC外)含量较结扎对侧和/或正常对照组明显增高，含水量：(91.14±2.21)% vs (82.99±6.53)% (P<0.05)，(91.44±2.21)% vs (87.22±1.13)%(P<0.05)，钙含量：(255.24±122.6) μmol/g干重 vs (44.12±13.54) μmol/g干重(P<0.01)，(255.24±122.6) μmol/g干重 vs (42.68±4.35) μmol/g干重(P<0.05)，NGF干预后，结扎侧脑组织含水量、组织钙含量及单胺类神经递质(除DOPAC)外含量均明显下降，与HIBD组结扎侧相比有显著性差异，与正常对照组相比无显著性差异。0.1 μg NGF组，含水量：(86.86±0.86)% vs (91.14±2.21)% (P<0.05)，钙含量：(44.34±3.10) μmol/g干重 vs (255.24±122.6) μmol/g干重(P<0.01)。0.3 μg NGF组，含水量：(87.45±0.37)% vs (91.14±2.21)% (P<0.05)，钙含量：(42.03±14.99) μmol/g干重 vs (255.24±122.6) μmol/g干重(P<0.01)。结论：NGF可以降低钙超载，减轻脑水肿，减弱或抑制单胺类神经递质等从而有可能减轻HIBD。

Ameliorative Effect of the Nerve Growth Factor

Objective To explore the mechanism of ameliorative effects of the nerve growth factor (NGF) on newborn rats with hypoxic ischemic brain damage (HIBD). Methods NGF dosage ( 0.1 μg/kg and 0.3 μg/kg) was administrated intraperitoneally to the rat pups 30 minutes before and immediately following the hypoxic exposure. The percentage of brain water content was determined according to the formula: (wet weight dry weight)/wet weight×100=% water content. Brain tissue calcium concentration was measured with atomic absorption spectroscopy. Monoamine neurotransmitter concentration in the rat brain was measured using high performance liquid chromatography with electrochemical detector (HPLC ECD). Results Brain water content, calcium conentration and monoamine neurotransmitters (except DOPAC) concentration increased significantly after hypoxic ischemic insult in the ipsilateral hemisphere of the HIBD group compared with the contralateral hemisphere and/or control group: water contents=(91.44±2.21)% vs (82.99±6.53)% (P<0.05) and ( 91.44 ± 2.21 )% vs ( 87.22 ± 1.13 )% (P< 0.05 ) respectively; calcium concentration=( 255.24 ± 122.6 ) μmol/g dry weight vs ( 44.12 ± 13.54 ) μmol/g dry weight (P< 0.01 ) and ( 255.24 ± 122.6 ) μmol/g dry weight vs ( 42.68 ± 4.35 ) μmol/g dry weight (P< 0.01 ), respectively. There were significant discreases in water content, calcium concentration and monoamine neurotransmitters (except DOPAC) concentration in the 0.1 μg/kg and 0.3 μg/kg NGF treated HIBD group (compared with untreated HIBD group): water contents=( 86.86 ± 0.86 )% and ( 87.45 ± 0.3 )%, respectively; calcium concentration=( 44.34 ± 3.10 ) μmol/g dry weight and ( 42.03 ± 14.99 ) μmol/g dry weight, respectively. No differene was found between the NGF group and control group. Conclusions Water content, calcium concentration and monoamine neurotransmitters may be involved, alone or interactively, in the pathophysiologic process of HIBD. NGF has ameliorative effects on newborn rats with HIBD, possibly through maintaining calcium homeostasis, ameliorating brain edema and attenuating or inhibiting the neurotoxic effects of monoamine neurotransmitters.