• 作者： 符文美；蕭水銀
• 作者服務機構： 國立臺灣大學醫學院藥理學科
• 中文摘要： 近十年來，由於闡明某些重金屬在體內所扮演的重要角色，如缺乏銅及鈷，會引起貧血症;缺少鋅會使小孩發育不良，胎兒畸形;缺乏錳及鎳可引起種種神經及骨骼肌之症狀等。因此，許多營養製劑如多種維生素片劑添加多種重金屬如錳、鈷、鎳、鋅及銅，可是不經意的多量攝取，加上自來水尤其是軟水可自水管溶解多量重金屬以及工廠重金屬廢物之不當處理，使得人們體內積蓄過多的重金屬，而引起致毒作用。雖然過去有些報告研究重金屬對神經及骨骼肌的作用，但尚未有將各種重金屬致毒作用的強弱及作用機轉作詳細的比較研究。本篇研究目的就是將九種金屬離子即錳、鈷、鎳、鎘、鋅、銅、鋇、鍶及鈾對小白鼠膈神經及橫膈膜之作用比較研究，並探求其作用機轉。 這九種金屬離子對小白鼠之膈神經—橫膈膜標本之作用方式不盡相同:錳、鈷、鎳、鋅，尤其鎘具有很強的神經肌傳導的阻斷作用，鍶之此作用則很微弱;錳全無，而鈷、鎳稍有攣縮作用，鋅及鎘之攣縮作用較強，而銅之攣縮作用及抑制電刺激之收縮作用一樣強。反之，鋇及鈾則加強橫膈膜對神經刺激之反應，但在高濃度對肌肉刺激之反應有直接的抑制作用。至於這些金屬離子作用之可逆性也不相同:錳、鋇之作用是可逆的，鈷、鎳、鎘及鈾(高濃度)之作用在短時間內是可逆，但作用長時問後則變成不可逆，而鋅及銅的作用是完全不可逆的。 探求這些金屬離子之作用機轉，則在金屬離子完全阻斷神經肌傳導後，加入高鈣或半胱胺酸，看其對抗情形:錳、鈷、鎳及鎘之作用皆可以鈣來對抗之，但鋅之作用則不能為鈣所對抗;半胱膿酸對抗鎘之作用最好，對抗鈷及鎳之作用很弱，而對鋅及銅的作用全無影饗;至於鋇增強橫膈膜之收縮作用可能對骨骼肌直接作用而來，因橫膈膜之收縮作用不論經由刺激神經或以箭毒素處理後直接刺激骨骼肌引起的，皆可為鋇所增強;而鈾之作用機轉與鋇就不相同，可能主要作用在膈神經末端，使乙醯膽鹼釋放而引起，因橫膈膜若經箭毒素處理後，直接刺激骨骼肌之收縮反應不為鈾所增強。 由這些結果得知這些金屬離子對神經及骨骼肌均有很強的作用，其作用機轉可能有些是與細胞膜之一SH基結合，影響細胞膜對鈣離子之滲透性，繼而影響神經末梢釋放乙醯膽鹼，及肌肉收縮之機轉，因已知二者之作用皆需鈣離子。
• 英文摘要： Effects of heavy metals including Mn++, Co++, Ni++, Cd++, Zn++, Cu++, Sr++, Ba++and UO2++ on the neuromuscular transmission of the mouse diaphragm were studied and compared. From the dose-inhibition curves, the concentrations (mM) required to inhibit 50% of the contraction (ID50) for Cd++, Mn++，Co++, Ni++, Zn++ and Sr++ are 0.03, 0.8, 0.75, 0.82, 1.2 and >20 respectively. In addition to the potent neuromuscular blocking action, both Cd++ and Zn++ induce a contracture of the mouse diaphragm. Among the cations tested, Cu++ is the most potent in inducing the contracture. Mn++ does not cause a contracture, while Co++ and Ni++ induce a contracture only after a prolonged incubation for 3 hrs. The neuromuscular blocking action of most of the cations tested can be completely or partially reversed by either high Ca++ or cysteine except the irreversible action of Zn++ and Cu++. These findings suggest that most divalent cations block the neuromuscular transmission by binding to the -SH group of the cell membrane and inhibiting Ca++ influx. On the other hand, both Ba++ and UO2++ at low concentration increase but at high concentration inhibit the twitch response. Since Ba++ increases the twitch response of the mouse diaphragm stimulated directly in the presence of d-tubocurarine as well as that stimulated indirectly, Ba++ acts mainly directly on the muscle. In contrast, UO2++ at low concentration increases the twitch response possibly by releasing acetylcholine from the nerve endings since d-tubocurarine inhibits this effect of UO2++ and acetylcholinesterase activity of the diaphragm is not affected by UO2++. However, UO2++ at high concentration inhibits the twitch response mainly due to the direct action on the muscle since the twitch response to either direct or indirect stimulation is simultaneously reduced by UO2++.
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