大黃 (Rhei Rhizoma) 在中國傳統醫學界一直被認為具有通利解毒、瀉下、利尿、抗發炎及抑制水腫等功效。大黃中藥用個別成分作用機制之研究已有相當深入的報導，但對於大黃整體作用機制，尤其是對於離子的影響等尚未見於文獻。在許\多諸如Lubiprostone等瀉下利尿藥物中，其機制常與上皮細胞對離子通透之改變有關。這便產生了大黃的瀉下利尿是否也可能具有相似的作用機制的問題。因此，本研究使用Ussing chamber技術觀察大黃水萃取物 (RRE) 對青蛙皮膜兩側短路電流的影響並分析實驗數據，以了解其對離子通道之影響。
實驗結果顯示，穩定時的蛙皮，其短路電流 (Isc) 約為59.23±5.58μA/cm²，電導值 (Gi)約 1.11±0.50μA/cm²•mV。 將RRE加入黏膜側後，可使短路電流上升90%。若隨後再加入鈉離子阻斷劑Amiloride，可降低136%之短路電流；若加入氯離子阻斷劑Chlorothiazide則可降低33%之短路電流。若將皮膜分別先以Amiloride 與 Chlorothiazide處理後再加入RRE，其短路電流分別上升24%及70%，明顯受到先加入之Amiloride與Chlorothiazide抑制。若是先加入Chlorothiazide與Amiloride處理皮膜後，則RRE的加入僅能使短路電流上升5%。我們以Na-free Ringer solution或Cl-free Ringer solution取代原先的Ringer solution處理皮膜，發現RRE所造成之短路電流也有明顯之降低。與一般Ringer solution之短路電流相比，其短路電流值降為16%與42%。由以上結果可知Amiloride與Chlorothiazide均可抑制RRE作用。
本實驗結果可作成以下幾點結論： (一) ，RRE主要影響黏膜側之短路電流。 (二) ，先以Amiloride處理皮膜後，RRE無法如單獨加入時顯著提升短路電流，顯示其主要功能為影響Na+之流動。但由於RRE仍可提升短路電流，代表RRE仍有部份功能為影響其他離子通道。 (三) ，先以Chlorothiazide處理皮膜後，RRE提升之短路電流有部分降低，顯示RRE有部分功能為影響Cl-離子通道。 (四) ，RRE在漿膜側之作用不明顯。

Rhei Rhizoma, also named as rhubarb or Da Huang, has been used widely in oriental traditional medicine in treating constipation and edema. However, though much affection has been paid to the make of components on pharmaceutical mechanisms, few studies have been conducted to reveal chemical and physical mechanism of these effects. Studies have shown that diarrhea causes imbalance of chloride and sodium ion movements via epithelium, we wondered if similar mechanism may apply to Rhei Rhizoma, a herbal drug which has been used to treat constipation in oriental medicine for thousands of years. The measurement of short-circuit current (Isc) has been used widely to estimate the ion transportation between mucosal and serosal side of epithelium. In this study, we used Ussing chamber technique to examine the alternation in membrane potential and short-circuit currents.
The result shows, at default, the Isc of frog skin we used was at 59.23±5.58μA/cm², and the conductance was at 1.11±0.50μA/cm²•mV. The lnjection of 1ml RRE to mucosal side of the frog skin leaded to a 90% elevation of the Isc. Followed by the application of Amiloride (sodium channel inhibitor) and Chlorothiazide (chloride channel inhibitor) to mucosal side of the epithelial skin, the observed Isc were then reduced 136% and 33% respectively. If RRE were applied after the adding of Amiloride or Chlorothiazide to the frog skin, then the Isc of the skin elevated only 24% and 70% respectively.
These results show that Rhei Rhizoma Extract (RRE) significantly increases Isc upon application to the mucosal side of the skin epithelium. Amiloride and Chlorothiazide will both inhibit the Isc induced by RRE, indicating activation of chloride channel and Amiloride-sensitive sodium channel of the epithelial tissue by RRE. After the regular Ringer solution used in the preparation was replaced by Na-free and Cl-free Ringer solution, the inhibition of Isc by RRE application could still be observed although the inhibition was trivia. These results indicate that RRE acts dominantly on mucosa side of the epithelium and can be used to enhance sodium transport and to stimulate the secretion of Cl- in the epithelium.

縮寫表 1
中文摘要 3
英文摘要 5
文獻回顧 7
研究目標 15
實驗方法及材料 16
實驗結果 23
討論 30
結論 38
參考文獻 74

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