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一种新型下丘脑肽对眼镜蛇毒和创伤诱导的神经元损伤的保护作用。

Protective effect of a new hypothalamic peptide against cobra venom and trauma-induced neuronal injury.

作者信息

Galoyan A A, Sarkissian J S, Kipriyan T K, Sarkissian E J, Chavushyan E A, Sulkhanyan R M, Meliksetyan I B, Abrahamyan S S, Avetisyan Z A, Otieva N A

机构信息

Bunatian Institute of Biochemistry, NAS RA, Yerevan, The Republic of Armenia.

出版信息

Neurochem Res. 2001 Sep;26(8-9):1023-38. doi: 10.1023/a:1012353005489.

Abstract

A study of separate and combined actions of cobra venom (CV) and a new hypothalamic proline-rich polypeptide (PRP) isolated from magnocellular cells (NPV and NSO) on intoxication- and trauma-induced neuronal injury (during 3-4 weeks after hemisection with and without PRP treatment) was carried out. The registration of background and evoked impulse activity flow, changes in spinal cord (SC) inter- and motoneurons, responding to flexor, extensor, and mixed nerve stimulation in both acute and chronic experimental neurodegeneration was performed. The facilitating effect of PRP on the abovementioned neurons was revealed. High doses of CV that evoked the neurodegenerative changes demonstrated an inhibitory effect. In this case PRP treatment both before and after intoxication restored electrical neuronal activity to baseline level and higher. These results are evidence of protective action of PRP. The low doses of CV induced a facilitating effect. The combination of CV and PRP displayed an additive facilitating effect; in a number of cases the repeated administration of CV led to decrease of significant PRP effect till baseline level (for example, the inhibition after primary response prior to secondary late discharge). Greater liability of the secondary early and late long-time discharges of poststimulus responses, differently expressed in various neuron types of SC to chemical influences is of interest. PRP-induced inhibition of the paroxysmal activity related with CV action is also very interesting. Morpho-functional experiments with SC injury demonstrated the abolition of difference in the background and evoked SC neuronal activity below the section and on intact symmetric side after daily PRP administration for 3 weeks. PRP hindered the scar formation and activated neuroglia proliferation; it promoted white matter element growth, hampered the degeneration of cellular elements, and protected against tissue stress. Our results favor the combined use of PRP and CV in clinical practice for the treatment of neurodegeneration of toxic and traumatic origin, as well as specific neurodegenerative diseases such as Alzheimer's.

摘要

开展了一项研究,观察眼镜蛇毒(CV)与一种从大细胞(NPV和NSO)中分离出的新型富含脯氨酸的下丘脑多肽(PRP)单独及联合作用于中毒和创伤诱导的神经元损伤(在有或无PRP治疗的半横切术后3 - 4周期间)的情况。在急性和慢性实验性神经退行性变中,记录了背景和诱发冲动活动流,以及脊髓(SC)中间神经元和运动神经元对屈肌、伸肌和混合神经刺激的反应变化。发现PRP对上述神经元有促进作用。诱发神经退行性变化的高剂量CV表现出抑制作用。在这种情况下,中毒前后的PRP治疗都将神经元电活动恢复到基线水平及更高水平。这些结果证明了PRP的保护作用。低剂量的CV产生促进作用。CV和PRP的组合表现出相加的促进作用;在一些情况下,重复给予CV会导致PRP的显著作用降低至基线水平(例如,在二次晚期放电之前的初级反应后的抑制)。刺激后反应的二次早期和晚期长时间放电在SC的不同神经元类型中对化学影响的不同表达更具研究意义。PRP诱导的与CV作用相关的阵发性活动抑制也非常有趣。对SC损伤进行的形态功能实验表明,在每天给予PRP 3周后,损伤部位以下和完整对称侧的背景和诱发的SC神经元活动差异消失。PRP阻碍瘢痕形成并激活神经胶质细胞增殖;它促进白质成分生长,阻碍细胞成分退化,并防止组织应激。我们的结果支持在临床实践中联合使用PRP和CV来治疗中毒性和创伤性神经退行性变以及阿尔茨海默病等特定神经退行性疾病。

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