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中药天花粉蛋白的逆向转运及其选择性神经毒性。

Retrograde transport of a traditional Chinese medicine, alpha-trichosanthin, and its selective neural toxicity.

作者信息

Shen Wei-Zai, Sha Ou, Yew David Tai-Wai, Kwong Wing-Hang

机构信息

School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.

出版信息

Clin Toxicol (Phila). 2009 Nov;47(9):876-83. doi: 10.3109/15563650903234713.

DOI:10.3109/15563650903234713
PMID:19852622
Abstract

OBJECTIVE

To investigate the peripheral neuronal toxicity of a traditional Chinese medicine, alpha-trichosanthin (TCS).

METHODS

TCS and rhodamine-conjugated TCS were separately injected into the rat sciatic nerve. Saline and rhodamine were used alone and separately as control solutions. The motor neurons in the spinal cord and sensory neurons in the dorsal root ganglia were separately counted. The entry of TCS molecules into neurons was observed under the fluorescence microscope. The glial reactions were studied by lectin staining and immunohistochemical method. The muscles innervated by the sciatic nerve and distal to the injection sites, and the nerves proximal to the injection sites were also collected and examined.

RESULTS

TCS was taken up and transported by peripheral axons, and at a dose of 1 nmol, killed more than 90% of the motor neurons in 5 days, but only one-third of the sensory neurons of the injected nerve. The loss of neurons was permanent, while the increase of glial activities was mild and transient.

CONCLUSION

TCS is retrogradely transported by axons of the injected nerve. TCS shows a selective neurotoxicity on different types of neurons. Hence TCS is useful in producing neural lesion in research, and this use may also be of applicational value in treating chronic spasticity, hyperalgesia, and pain.

摘要

目的

研究中药天花粉蛋白(TCS)的外周神经毒性。

方法

将TCS和罗丹明标记的TCS分别注入大鼠坐骨神经。单独使用生理盐水和罗丹明分别作为对照溶液。分别计数脊髓中的运动神经元和背根神经节中的感觉神经元。在荧光显微镜下观察TCS分子进入神经元的情况。通过凝集素染色和免疫组化方法研究胶质细胞反应。还收集并检查坐骨神经支配的、注射部位远端的肌肉以及注射部位近端的神经。

结果

TCS被外周轴突摄取并运输,剂量为1 nmol时,在5天内杀死了超过90%的运动神经元,但仅杀死了注射神经中三分之一的感觉神经元。神经元的损失是永久性的,而胶质细胞活性的增加是轻微且短暂的。

结论

TCS通过注射神经的轴突逆行运输。TCS对不同类型的神经元表现出选择性神经毒性。因此,TCS在研究中可用于制造神经损伤,这种用途在治疗慢性痉挛、痛觉过敏和疼痛方面也可能具有应用价值。

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