新生大鼠缺氧缺血性脑病模型脑组织钙调蛋白测定及脑活素治疗作用

Calmodulin in Brain Tissues of Newborn Rats with Hypoxic Ischemic Encephalopathy and the Therapeutic Effect of Cerebrolysin

摘要:

目的：研究脑组织中钙调蛋白(CaM)含量与新生大鼠缺氧缺血性脑病(HIE)发病机制的关系及脑活素的治疗作用。方法：在建立新生大鼠HIE模型的基础上，采用依赖环核苷酸的磷酸二酯酶(PDE)法检测103只大鼠(其中对照组15只，实验组88只分3组)脑组织CaM含量，结合病理切片和透射电镜观察脑组织病理改变，同时通过侧脑室及肌内两种途径给予脑活素治疗。结果：HIE组脑组织CaM含量均明显增高，24 h(521.27±46.04) μg/g脑组织；48 h(509.52±35.98) μg/g脑组织；72 h(421.05±31.81) μg/g脑组织，与正常组(187.63±54.22)比较差异有显著性(P<0.01)；治疗组CaM含量均明显降低，侧脑室注射组：24 h(435.21±56.17) μg/g脑组织；48 h(260.38±32.43) μg/g脑组织；72 h(197.64±19.21) μg/g脑组织；肌内注射组：24 h(441.04±30.66) μg/g脑组织；48 h(305.39±32.99) μg/g脑组织；72 h(217.71±52.89) μg/g脑组织；与HIE组比较差异有显著性(P<0.01)，接近正常组水平。在神经元变性、坏死和间质水肿等方面，治疗组明显轻于HIE组。结论：CaM含量异常升高在HIE的发病环节中起一定作用。脑活素治疗HIE的机制可能与其显著降低脑组织中CaM含量有关。

Abstract:

OBJECTIVE: To study the relationship between calmodulin (CaM) concentrations in brain tissues of newborn rats and the pathogenesis of hypoxicischemic encephalopathy (HIE) and the therapeutic effect of cerebrolysin on HIE. METHODS: Morphological and metabolic effects of cerebral ischemia were investigated in a newborn rat model of neonatal HIE. In addition, the effect of cerebrolysin (EBEWE, Austria) on acute brain hypoxicischemia was studied. Eighty eight HIE newborn rats (48 cerebrolysintreated and 40 controls) were subjected to left cerebral artery ligation and one hour later they were placed in a hypoxic environment (8% oxygen and 92% nitrogen mixed) for two hours. Immediately afterwards, cerebrolysin (2.5 ml/kg body mass) was administered daily, either by intracerebroventricular infusion (i.c.v) or by intramuscular injection. CaM concentrations were determined using cyclicnucleotide dependent phosphodiesterase methods, and 15 normal rats were used as the control group. RESULTS: CaM concentrations in brain tissues increased in HIE group at different duration after hypoxicischemia: 24 h=(521.27±46.04) μg/g brain tissue; 48 h=(509.52±35.98) μg/g brain tissue; 72 h=(421.05±31.81) μg/g brain tissue, compared to the control group ［(187.63±54.22) μg/g brain tissue］ (P<0.01). Cerebrolysin treatment groups facilitated recovery, as indicated by a decrease in CaM concentration (i.c.v group: 24 h=(435.21±56.17) μg/g brain tissue; 48 h=(260.38±32.43) μg/g brain tissue; 72 h=(197.64±19.21) μg/g brain tissue; i.m.group: 24 h=(441.04±30.66) μg/g brain tissue; 48 h=(305.39±32.99) μg/g brain tissue; 72 h=(217.71±52.89) μg/g brain tissue (P<0.01). Morphological examination showed that the volume of neuron degeneration, necrosis and intercellular edema was increased in HIE groups and significantly reduced in cerebrolysin treatment groups. CONCLUSIONS: CaM concentration in brain tissues is increased after hypoxicischemic injury and may be implicated in the pathogenesis of newborn rats with HIE. Cerebrolysin is effective in protecting brain cells from further damage through its influence on cerebral CaM concentration.