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[摘要]
目的 研究注射用腦蛋白水解物(Ι)對血管性癡呆大鼠的神經保護作用機制。方法 采用改良兩血管阻斷法制備血管性癡呆(VaD)大鼠模型,假手術組僅分離頸總動脈不阻斷血管。將大鼠隨機分為假手術組、模型組、注射用腦蛋白水解物(Ι)低、中、高劑量(5、10、20 mg/kg)組和腦蛋白水解物注射液(Cerebrolysin,陽性藥,10 mg/kg)組。尾iv給藥,每天1次,連續(xù)給藥2周;假手術組和模型組給予等體積生理鹽水。給藥結束后,腹主動脈采血分離血清,分離大鼠皮層制備勻漿,ELISA法檢測VaD大鼠血清中神經生長因子(NGF)和胰島素樣生長因子2(IGF-2)水平、皮層中γ-氨基丁酸(GABA)水平,比色法檢測皮層中谷氨酸(Glu)水平。結果 與模型組比較,注射用腦蛋白水解物(Ι)顯著升高VaD大鼠血清中NGF、IGF-2水平、皮層中GABA水平,顯著降低VaD大鼠皮層中Glu水平;其升高IGF-2和GABA水平的作用優(yōu)于同劑量Cerebrolysin。結論 注射用腦蛋白水解物(Ι)提高VaD大鼠學習記憶能力的作用機制,可能與升高機體NGF、IGF-2水平,調節(jié)興奮性及抑制性氨基酸類神經遞質平衡有關。
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[Abstract]
Objective To investigate the neuroprotective mechanisms of Cerebroprotein Hydrolysate for Injection (Ι) on vascular dementia in rats. Method The rat vascular dementia model was prepared using an improved two-vessel occlusion 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 (Ι) 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 (Ι). The increased IGF-2 and GABA levels by Cerebroprotein Hydrolysate for Injection (Ι) 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 (Ι), 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.
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