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題名 | 硃砂經水飛法炮製後在鼷鼠體內的吸收,排泄及神經行為毒性的探討=Studies on Absorption, Excretion and Neurobehavioral Toxicities of Cinnabar Purified by Water Floating Processing in Mice |
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作者姓名(中文) | 楊榮森; 蕭水銀; | 書刊名 | 中醫藥年報 |
卷期 | 28:6 2010.09[民99.09] |
頁次 | 頁207-243 |
分類號 | 414.5 |
關鍵詞 | 水飛硃砂; 鼷鼠; 神經行為; 吸收; 排泄; 組織分佈; Cinnabar; Mice; Neurobehavioral effect; Absorption; Excretion; Tissue distribution; |
語文 | 中文(Chinese) |
中文摘要 | 硃砂在神農本草經,歸屬於有效無毒的上品藥物,二千多年來,中醫師 廣泛使用硃砂治療心神不寧,驚癲癇狂、失眠多夢、咽喉腫痛及癰疽瘡瘍等 宿疾。由於水飛硃砂含硫化汞成分95%以上,而且極不易溶解於任何溶劑, 因此硃砂在體內吸收,排泄、組織分布及對組織細胞的親和力及生物作用機 制等等,應與劇毒甲基汞有很大的差異性,因此,本研究計畫的目的,在於 闡明硃砂藥理及毒理動力學及作用學(即硃砂在鼷鼠體內的吸收,排泄及組 之分佈的研究)。 本研究餵水飛硃砂後,再分析其在鼷鼠體內吸收,排泄及組織分佈。由 於市售水飛珠砂種類很多,我們先選擇三種,經ICP/mass分析所含Hg及其他 微量元素,結果顯示編號硃砂C所含有毒金屬(Pb,Cd,As)最低,因此本研究均 採用硃砂C,另外硃砂劑量的選擇,乃根據我們實驗室研究結果,在低劑量 10mg/kg/day 5週,仍安全,由此我們設計使用硃砂劑量為30,100,300/mg/kg/day,餵食十八天,期能在各組織Hg含量足夠能測得到。 實驗結果,硃砂對鼷鼠神經行為的影響是活動量稍降,情緒稍低,跳躍探索些微下降,對攀爬運動平衡功能及學習記憶功能尚無影響,腦組織氧自 由基稍降,而NO在低劑量增加,高劑量下降,Na+-K+ ATPase在腦組織不同 部位作用不同,總體而言,低劑量促進,高劑量有抑制現象。分析鼷鼠各組 織,尿液及糞便Hg含量,結果顯示各組織含Hg總量排行依序(由大到小) 為腎臟,毛髮,血液,肝臟,腸,尿液,腦,胃,心臟及脾臟。而尿液及糞 便Hg含量,隨劑量及累積時日餵食而逐漸增加,總和各組織吸收Hg量及糞 便Hg排泄量,估算硃砂在鼷鼠體內之吸收與劑量有密切相關,低劑量(30及100mg/kg/day)吸收率約5%,但高劑量吸收率為1.6%,因此,硃砂排泄率低 劑量為95%,高劑量為98.4%,本實驗結果,闡明硃砂的毒性遠不如一般所熟知的劇毒甲基汞(吸收率大於90%),也証實以前我們實驗結果顯示硃砂神 經毒性是甲基汞的五千分之一至一千分之ㄧ。至於高劑量(300mg/kg/day)硃砂 在腸胃吸收,不如低劑量的原因,據推測可能高劑量對腸胃吸收以有不良的 作用產生,此推測有待以後做實驗證實。 有關硃砂降低活動量(鎮靜安神作用)及其他神經行為之作用,是很 重要的議題,依照我們過去初步的研究,有些行為作用是可逆性的,但我們 必須強調硃砂品質非常有關係,有些是受硃砂含重金屬,有可能導致不可逆 性傷害,由本研究結果及過去歷年的實驗結果,初步評估:(1)在嚴格管制的 優良水飛硃砂。(2)中醫師嚴謹的調控硃砂劑量。(3)短暫的使用期限制(5-7 天)。(4)現仍無硃砂的取代品。則硃砂在中醫藥品項可考慮存在,但此重要 議題仍須再以專題做進一步的研究。 |
英文摘要 | This study focused on the absorption excretion and tissue distribution of cinnabar fed to mice. The quality and metal contaminants of three commercial cinnabar samples were analyzed by ICP/mass. The results showed that one of them had much smaller contaminant of Pb. Cd and As. Thus, cinnabar C was used throughout the experiments. The dosage of cinnabar chosen (30, 100 and 300mg/kg/ day) according to our previous results would not produce renal and hepatic toxicity. During the period of cinnabar administration, the changes of neurobehavioral effects were continuously monitored. It indicated that cinnabar exhibited a slight depressant effect on locomotor activities, jump and exploring behavior, a slight decrease in retention time in open field of plus maze. There were no significant effect on climbing and rotarod motor equilibrium performance. The free radical production in brain was decreased by high dose, and NO production was increased by low dose but increased by high dose, while Na+-K+-ATPase activity was also increased by low dose and decreased by high dose of cinnabar. The tissue contents of Hg in various tissues showed that kidney is the highest and then hair, blood, liver, intestine, urine, brain, stomach, heart and spleen in order. The amount excreted in urine and feces were gradually increased following the continuous feeding, suggesting the cumulative effects of cinnabar. The estimated absorption rates of cinnabar were 4.5%, 5.5% and 1.6% in response to the doses of 30, 100 and 300mg/ kg/day respectively. Accordingly, the excretion rate of cinnabar in feces were 95.5%, 94.5% and 98.6% respectively, suggesting that the higher doses of cinnabar were limited by the lowering absorption. These findings provide a fact that cinnabar is actually not so toxic as the well-known toxic methylmecury (the absorption rate is greater than 90%), because of its very poor aborption. These results were also correlated our previous findings that the neurotoxic effect of cinnabar is ranging one thousandth to five thausandth of that of methylmercure. |
本系統之摘要資訊系依該期刊論文摘要之資訊為主。