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題 名 | 硃砂單方及八寶散硃砂複方對幼鼠之鎮靜安神及毒性研究=Studies of Sedative and Toxic Effects of the Single and Compunded Cinnabar in Young Mice |
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作 者 | 蕭水銀; | 書刊名 | 中醫藥年報 |
卷 期 | 24:1 民95.10 |
頁 次 | 頁1-27 |
專 輯 | 中醫藥療效評估之研究 |
分類號 | 414.36 |
關鍵詞 | 幼鼷鼠; 單方硃砂; 八寶散硃砂複方; 鎮靜安神; 神經毒性反應; Compounded cinnabar; Toxicity; Young mice; |
語 文 | 中文(Chinese) |
中文摘要 | 我們研究室有關硃砂及硫化汞的研究成果中,發現硃砂及硫化汞的神經毒性大小僅約為一般大家所熟知的劇毒--甲基汞的千分之一,比其他重金屬,如氯化銅,氯化鉛或氯化鎘的急性毒性小。同時對於市售傳統水飛硃砂之毒性及安全劑量的研究結果推估出成人使用水飛硃砂的安全劑量為0.05g~0.07g/day,連續重複使用最好不超過10-14天。然而我們這些研究成果是根據硃砂或硫化汞餵食成熟鼷鼠後所測試之各項實驗所得結論。我們都知道中醫在臨床上常使用硃砂作為嬰幼兒的鎮靜安神劑,其中又以複方加味硃砂最常用。因此我們認為研究硃砂對於幼鼷鼠的神經藥理作用(鎮靜安神)及毒性反應,乃當前迫切急需闡明的重要課題!此外,中醫師對於硃砂的使用常以複方為主,鮮少以單方獨自使用,而硃砂與其他中藥合用下,硃砂的藥效是否有改變,也是值得我們去詳加探討的問題。所以我們擬於本計畫研究及探求單方及複方硃砂對於幼鼷鼠所產生的神經藥理作用及毒性反應,以便瞭解單方與複方硃砂所產生的作用反應有何異同?同時也能進一步瞭解硃砂在成鼠及幼鼷鼠中所造成的鎮靜安神及毒性作用的差異性。因此,我們在本研究計畫中的研究重點是:(1)探求市售傳統水飛硃砂(0.01g/kg),在幼鼷鼠體內的吸收、鎮靜安神、神經毒性的劑量及效應關係,並探討硃砂對幼鼠及成鼠作用的差異性。(2)複方硃砂在幼鼷鼠體內的吸收、鎮靜安神及神經毒性的劑量及效應關係,與單獨硃砂的劑量-效應關係之差異性作比較研究。餵食幼鼷鼠複方硃砂(硃砂劑量減為0.004g/kg)及對照組,在餵食一星期、二星期或更久--十一星期(依照產生的藥理及毒理作用再作決定),分析對幼鼷鼠所產生鎮靜安神的效用(活動力、安靜不活動期、跳躍次數,及對pentobarbital睡眠期延長效率)及產生毒性(耳毒性-聽力誘發腦幹訊息傳遞機制,旋轉輪平衡運動效率,血液及腦組織NO含量,腦組織Na+-K+-ATPase活性的改變)。 本研究成果歸納如下:(1)幼鼷鼠餵食硃砂低劑量4mg/Kg鎮靜安神的效果不亞於10mg/Kg,因此幼鼠對硃砂的反應顯然比成鼠敏感且藥效確實。(2)使用低劑量硃砂(4mg/Kg)6-7星期神經毒性(耳毒性及運動平衡能力)均不明顯,因此低劑量硃砂(4mg/Kg)對幼鼠鎮靜安神作用明顯,而且連續使用一個半月尚在安全期限內。(3)複方硃砂之鎮靜安神效果及神經毒性,均趨向緩和的效應。最明顯的良好效應是在單方硃砂餵食11星期後,運動均失調,但複方硃砂尚無此毒性作用產生。(4)單方硃砂明顯增加血液中及小腦組織NOx含量,而複方硃砂則明顯緩和此NOx增加之作用。(5)複方硃砂選擇性的增加小腦NOx含量,不影響血中NOx含量,顯示其對腦組織作用的特異性。(6)最重要的是單方硃砂明顯抑制腦組織中Na+-K+-ATPase活性,而複方硃砂也使Na+-K+-ATPase活性抑制作用較小。總之,本研究結果顯示硃砂對幼鼠鎮靜安神之效果比成鼠良好,更低劑量(4mg/Kg)就有效,也因此安全使用期限也由14天增至45天左右。而複方硃砂之鎮靜安神效果較緩和,但神經毒性明顯下降。 |
英文摘要 | In our previous experiments, we have demonstrated that cinnabar and HgS exhibited neurotoxic effect in guinea-pigs, rats and mice to be ranged at one thousandth of those methymercury. This finding indicates the fact that the toxic effects of cinnabar and HgS are less than those of CuCl₂ and CdCl₂. In order to extimate the approximate safe range of dosage of cinnabar, we have performed the experiments in assessing the dosage regimen in inducing sedative effects and neurotoxic effects respectively. The results obtained lead us to estimate the safe dosage regimen to be in the range of 0.05-0.07g/day, once everday for 10-14 days. However, this estimation is based on the restricted conditions performed in the adult mice. One important question regarding the pharmacological effects of cinnabar in the infants or neonatal mice is still awaited to be elucidated. Therefore, We attempted in this research project to investigate the sedative and neurotoxic effects of cinnabar in younger mice immediately after discontinuous mother feeding (21 days postneonatal). In addition, we will study the efficacy of compounded cinnabar as compared with the single cinnabar, since it is clinically to prescribe cinnabar in compound formulation. The results obtained in this study include: (1) The sedative effects of a lower dose (4mg/Kg) of cinnabar to the young mice were superior to 10mg/Kg in adult mice. Apparently the response of young mice to cinnabar is much better than that of adult mice. (2) At this lower dose of 4mg/Kg of cinnabar, the neurotoxic effects including hearing defect and imbalanced motor performance were not exhibited with prolonged feeding for more than 45 days. (3) The pharmacological and neurotoxic effects of compounded cinnabar tends to become moderately. The most prominent beneficial effects of compounded cinnabar is that the imbalanced motor performance which usually appeared after 10-11 wks-feeding of cinnabar alone was not yet induced in the mice fed with compounded cinnabar. (4) NOx contents of the blood and cerebellar cortex were significantly increased by singled cinnabar but were much less by compounded cinnabar. (5) The selective increase of cerebellar NOx contents by compounded cinnabar suggests its specific effect on CNS. (6) The most important event found in the brain is that Na+-K+-ATPase activity is inhibited with less extent by compounded cinnabar. All of these findings suggest that the younger mice are definitely more responsive to the sedative effects of cinnabar which allow to use a lower dose of cinnabar with a better therapeutic index, and the compounded cinnabar possesses a moderate sedative effect associated with less neurotoxic effect. These results provide the useful information that the lower effective compounded cinnabar used in the young mice markedly enhanced the therapeutic index of cinnabar. |
本系統中英文摘要資訊取自各篇刊載內容。