Torii K, Takasaki Y
Brain Res Bull. 1987 Apr;18(4):547-54. doi: 10.1016/0361-9230(87)90118-3.
Neonatal mice, under fasting conditions, are susceptible to the development of lesions in the arcuate nucleus (AN) of the hypothalamus, with high doses of monosodium L-glutamate (MSG). Feeding of nutrients (e.g., sugars and L-amino acids) has been shown to have a protective effect against the development of these lesions. The purpose of these studies was to elucidate the mechanism of this protective effect. Histopathologic examination of lesions of the AN demonstrated that feeding of weaning mice before subcutaneous administration of toxic doses of MSG suppressed the development of these lesions, as compared to fasted controls. Similarly, the number of necrotic cells in the AN of neonates administered toxic doses of MSG subcutaneously was reduced when D-glucose and L-arginine were administered orally. Atropine obliterated the protective effect of D-glucose. Pretreatments consisting of gastric inhibitory polypeptide (GIP) + oral D-glucose had a protective effect of higher potency than GIP alone. Pretreatments with insulin, anorexigenic peptide (pyroGlu-His-Gly), cholecystokinin, glucagon, bombesin, and substance P (in decreasing order of effectiveness) demonstrated a protective effect against the AN lesion in neonates, whereas somatostatin and beta-endorphin had no effect. Results suggest that the protective effect of nutrients may in part be due to the stimulation of peptide hormone release during the postabsorptive phase. It is postulated that the effect of entero-pancreatic hormone, especially insulin, is to enhance the tolerance of AN neurons of neonatal mice to the toxic dose of L-glutamate.
在禁食条件下，新生小鼠经高剂量L-谷氨酸钠（MSG）处理后，下丘脑弓状核（AN）易出现损伤。研究表明，给予营养物质（如糖类和L-氨基酸）对这些损伤的发生具有保护作用。这些研究的目的是阐明这种保护作用的机制。对AN损伤的组织病理学检查显示，与禁食对照组相比，在皮下注射毒性剂量的MSG之前给断奶小鼠喂食可抑制这些损伤的发生。同样，口服D-葡萄糖和L-精氨酸可减少皮下注射毒性剂量MSG的新生小鼠AN中坏死细胞的数量。阿托品消除了D-葡萄糖的保护作用。由胃抑制多肽（GIP）+口服D-葡萄糖组成的预处理比单独使用GIP具有更高的保护效力。用胰岛素、厌食肽（焦谷氨酸-组氨酸-甘氨酸）、胆囊收缩素、胰高血糖素、蛙皮素和P物质进行预处理（按有效性递减顺序）对新生小鼠的AN损伤具有保护作用，而生长抑素和β-内啡肽则无作用。结果表明，营养物质的保护作用可能部分归因于吸收后阶段肽类激素释放的刺激。据推测，肠胰激素尤其是胰岛素的作用是增强新生小鼠AN神经元对毒性剂量L-谷氨酸的耐受性。
