注射用脑蛋白水解物(Ⅰ)对血管性痴呆大鼠的神经保护作用机制

Neuroprotective effects and mechanisms of Cerebroprotein Hydrolysate for Injection (Ⅰ) on vascular dementia in rats

目的研究注射用脑蛋白水解物(Ⅰ)对血管性痴呆大鼠的神经保护作用机制。方法采用改良两血管阻断法制备血管性痴呆(Va D)大鼠模型,假手术组仅分离颈总动脉不阻断血管。将大鼠随机分为假手术组、模型组、注射用脑蛋白水解物(Ⅰ)低、中、高剂量(5、10、20 mg/kg)组和脑蛋白水解物注射液(Cerebrolysin,阳性药,10 mg/kg)组。尾iv给药,每天1次,连续给药2周;假手术组和模型组给予等体积生理盐水。给药结束后,腹主动脉采血分离血清,分离大鼠皮层制备匀浆,ELISA法检测Va D大鼠血清中神经生长因子(NGF)和胰岛素样生长因子2(IGF-2)水平、皮层中γ-氨基丁酸(GABA)水平,比色法检测皮层中谷氨酸(Glu)水平。结果与模型组比较,注射用脑蛋白水解物(Ⅰ)显著升高Va D大鼠血清中NGF、IGF-2水平、皮层中GABA水平,显著降低VaD大鼠皮层中Glu水平;其升高IGF-2和GABA水平的作用优于同剂量Cerebrolysin。结论注射用脑蛋白水解物(Ⅰ)提高Va D大鼠学习记忆能力的作用机制,可能与升高机体NGF、IGF-2水平,调节兴奋性及抑制性氨基酸类神经递质平衡有关。

Objective To investigate the neuroprotective mechanisms of Cerebroprotein Hydrolysate for Injection （1） on vascular dementia in rats. Method The rat vascular dementia model was prepared using an improved two-vessel oeelusion method, and the common carotid artery was only isolated but not blocked in sham group. Rats were randomly divided into sham group, model group, Cerebroprotein Hydrolysate for Injection （I） groups with low, medium and high dose （5, 10, 20 mg/kg） and Cerebroprotein Hydrolysate Injection group （Cerebrolysin, Positive drug, 10 mg/kg）. The drug was administered by iv injection of rat tail vein once a day for two weeks, while the same volume of saline was administered in sham and model group. At the end of administration, the plasma was collected through abdominal aorta to separate serum, and rat cortex was isolated to prepare homogenate. The levels of nerve growth factor （NGF） and insulin-like growth factor 2 （IGF-2） in serum and level of gamma-aminobutyric acid （GABA） in cortex were detected by ELISA. Level of glutamate （Glu） in cortex of VaD rats was detected by colorimetry. Results Compared with model group, levels of NGF and IGF-2 in the serum of VaD rats and level of GABA in cortex were significantly increased, while level of Glu in cortex was significantly decreased after administration of Cerebroprotein Hydrolysate for Injection （I）. The increased IGF-2 and GABA levels by Cerebroprotein Hydrolysate for Injection （I） were significantly higher than that of Cerebrolysin at same dose. Conclusion The mechanisms underlying the increased learning and memory ability of VaD rats by Cerebroprotein Hydrolysate for Injection （I）, are possibly related to the increased levels of NGF and IGF-2 in body and a regulation of the balance between excitatory and inhibitory amino acid neurotransmitters.