山黧豆神经性中毒机理的研究进展

Recent Progress on the Neurolathyrism Mechanisms

山黧豆(Lathyrus sativas L.)是优良的旱地作物种质资源,但长期过量食用会导致人畜神经性山黧豆中毒(neurolathyrism)。山黧豆中毒是一种发生在人类和动物中的神经退行性疾病,在发展中国家(如印度、孟加拉国、巴基斯坦、尼泊尔、埃塞俄比亚和我国西北等地区)时有发生,但其细胞及分子机理尚不明确。研究山黧豆中毒的致病机理对防止山黧豆中毒和中毒后的有效治疗具有重要意义。已有的研究表明,β-N-草酰-L-α,β-二氨基丙酸(β-N-oxalyl-L-α,β-diaminopropionic acid,β-ODAP)为主要致病毒素,其可通过干扰谷氨酸的正常功能、破坏神经细胞内钙稳态、加剧氧化胁迫并破坏线粒体的功能等来诱发神经细胞损伤或死亡,阻断交感神经对肌肉的控制,最终导致人下肢或动物后肢肌肉萎缩和不可逆瘫痪。文章综述了近年来神经性山黧豆中毒的机制研究,对今后的研究提供参考和借鉴。

Grass pea （Lathyrus sativas L.） has received great interests as an arid-adapted plant over the past several decades. Long-term excessive consumption of Lathyrus sativus seeds is considered as the cause of neurodegenerative disease neurolathyrism, which is a form of human and animal spastic paraparesis. Neurolathyrism often occurs in developing countries including India, Bangladesh, Pakistan, Nepal, Ethiopia, Northwest China and other regions. Studies on the mechanisms of neurolathyrism contribute importantly to its prevention and treatment. Previous researches indicate that the neurotoxin β-N-oxalyI-L-α,β-diaminopropionic acid （β-ODAP） acts as an excitotoxic substance, which is a nonprotein amino acid existing in Lathyrus sativus seeds and a competitive agonist of the glutamate receptors, disturbs the intracellular Ca^2＋ homeostasis, enhances oxidative stress and causes mitochondria injury, induces damage or death of the nerve cells, blocks the control of sympathetic nerve in muscles, eventually causes the atrophy and irreversible paralysis in human lower limb or animal hind limb muscle. The recent progresses in mechanisms of neurolathyrism are reviewed in this paper.