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蝎毒耐热肽对6羟多巴早期帕金森病大鼠的神经保护作用

殷盛明, 赵丹, 于德钦, 李盛龙, 安冬, 彭岩, 徐红, 孙艺平, 王冬梅, 赵杰, 张万琴

大连医科大学生理教研室；机能实验室，大连 116044

摘要

本文旨在研究蝎毒耐热肽(SVHRP)是否可以缓解早期帕金森病(Parkinson’s disease, PD)模型中脑神经元线粒体超微结构异常和氧化应激。将6羟多巴(6-OHDA, 20 μg/3 μL含0.1%抗坏血酸生理盐水)单侧注射到Sprague Dawley (SD)大鼠纹状体制备早期PD模型，PD大鼠腹腔注射SVHRP或相同体积对照溶液(生理盐水)处理1周。在6-OHDA注射2周后，对大鼠进行行为学检测；6-OHDA注射3周后，用免疫组织化学法检测多巴胺能神经元的免疫反应活性，用电子显微镜观察中脑神经元线粒体的超微结构，用试剂盒检测中脑神经元线粒体的单胺氧化酶B活性、超氧化物歧化酶活性和丙二醛含量，并进一步检测血清抑制羟自由基能力和抗氧化能力。结果显示，早期PD大鼠多巴胺能神经元的光密度相对对照组明显降低，中脑神经元线粒体超微结构的损伤显著加重，超氧化物歧化酶活性明显下降，单胺氧化酶B活性和丙二醛含量显著升高，血清抑制羟自由基能力和总的抗氧化能力显著下降。而SVHRP能够明显逆转6-OHDA的上述损伤作用。以上结果提示，SVHRP通过减轻早期PD的异常氧化应激和超微结构的损伤来发挥神经保护作用。

关键词： 蝎毒; 帕金森病; 线粒体; 抗氧化

分类号：R741

Neuroprotection by scorpion venom heat resistant peptide in 6-hydroxydopamine rat model of early-stage Parkinson’s disease

YIN Sheng-Ming, ZHAO Dan, YU De-Qin LI Sheng-Long, AN Dong, PENG Yan, XU Hong, SUN Yi-Ping, WANG Dong-Mei, ZHAO Jie, ZHANG Wan-Qin

Department of Physiology； Laboratory of Function, Dalian Medical University, Dalian 116044, China

Abstract

Neuroprotective effect of scorpion venom on Parkinson's disease (PD) has already been reported. The present study was aimed to investigate whether scorpion venom heat resistant peptide (SVHRP) could attenuate ultrastructural abnormalities in mitochondria and oxidative stress in midbrain neurons of early-stage PD model. The early-stage PD model was established by injecting 6-hydroxydopamine (6-OHDA) (20 μg/3 μL normal saline with 0.1% ascorbic acid) into the striatum of Sprague Dawley (SD) rats unilaterally. The rats were intraperitoneally administered with SVHRP (0.05 mg/kg per day) or vehicle (saline) for 1 week. Two weeks after 6-OHDA treatment, the rats received behavior tests for validation of model. Three weeks after 6-OHDA injection, the immunoreactivity of dopaminergic neurons were detected by immunohistochemistry staining, and the ultrastructure of neuronal mitochondria in midbrain was observed by electron microscope. In the meantime, the activities of monoamine oxidase-B (MAO-B), superoxide dismutase (SOD) and content of malondialdehyde (MDA) in the mitochondria of the midbrain neurons, as well as the inhibitory ability of hydroxyl free radical and the antioxidant ability in the serum, were measured by corresponding kits. The results showed that 6-OHDA reduced the optical density of dopaminergic neurons, induced damage of mitochondrial ultrastructure of midbrain neurons, decreased SOD activity, increased MAO-B activity and MDA content, and reduced the antioxidant ability of the serum. SVHRP significantly reversed the previous harmful effects of 6-OHDA in early-stage PD model. These findings indicate that SVHRP may contribute to neuroprotection by preventing biochemical and ultrastructure damage changes which occur during early-stage PD.

Key words: scorpion venom; Parkinson’s disease; mitochondria; antioxidation

收稿日期：2014-03-31　　录用日期：2014-06-10

通讯作者：殷盛明,赵杰　　E-mail: dlshengming@163.com,

引用本文：

殷盛明, 赵丹, 于德钦, 李盛龙, 安冬, 彭岩, 徐红, 孙艺平, 王冬梅, 赵杰, 张万琴. 蝎毒耐热肽对6羟多巴早期帕金森病大鼠的神经保护作用[J]. 生理学报 2014; 66 (6): 658-666.

YIN Sheng-Ming, ZHAO Dan, YU De-Qin LI Sheng-Long, AN Dong, PENG Yan, XU Hong, SUN Yi-Ping, WANG Dong-Mei, ZHAO Jie, ZHANG Wan-Qin. Neuroprotection by scorpion venom heat resistant peptide in 6-hydroxydopamine rat model of early-stage Parkinson’s disease. Acta Physiol Sin 2014; 66 (6): 658-666 (in Chinese with English abstract).