臺灣博碩士論文加值系統

使用中藥及處方治療疾病在中國已有幾千年的歷史。黃芩(Huang Qin) 唇形科(Labiatae) 植物Scutellaria baicalensis Georgi之乾燥根，為中藥安胎方劑常配伍之中藥材，但卻無相關之科學化研究。本研究第一部份首先以現代藥理學之技術，評估黃芩水抽出物及其成分Baicalin、Baicalein、Oroxylin A、Wogonin之安胎作用，發現黃芩水抽取物高劑量時對懷孕初期(第10天) 離體雌性大白鼠子宮平滑肌收縮有意義抑制作用，IC50為4.98 + 1.12 mg/ml,由結果證實，黃芩具有安胎活性物質。因此乃再進行四種黃芩成分Baicalin、Baicalein、Oroxylin A、Wogonin 對懷孕初期(第10天)離體子宮平滑肌之收縮抑制作用，IC50分別為67.22 + 5.75μM，59.71 + 6.67μM，50.38 + 4.91μM，71.11 + 5.11μM，證實此四種flavonoid類成分具有安胎活性。繼而進行第二部份四種活性主成分之作用機制探討。
黃芩成分對Acetylcholine ( ACh；10-6 M )，Prostaglandin F2a ( PGF2a；10-7 M )，Oxytocin (10-3 U/ml) 誘發離體子宮平滑肌收縮皆有抑制作用，並證實黃芩成分- Baicalein 與Oroxylin A產生子宮鬆弛之活性與膜電位之極化、去極化有關，並配合藥理學研究使用鉀離子阻斷劑tetraethylammonium ( TEA; 1 and 10 mM ), 4-aminopyridine ( 4-AP ; 5 mM ), glipizide ( 30μM )，經實驗結果證實Baicalein 與Oroxylin A造成子宮鬆弛乃經由活化鉀離子通道之通透性，方造成子宮鬆弛，但Baicalin與Wogonin卻發現與鉀離子之作用機制無關；Baicalin與Wogonin之安胎機轉與外鈣流入及/或內鈣釋放子宮平滑肌鬆弛作用機制有相關性，且可活化β-adrenergic receptor及對cyclooxygenase具抑制作用。綜合以上結果，黃芩具有安胎作用，其安胎活性成分為Baicalin、Baicalein、Oroxylin A、Wogonin。

Chinese medicinal prescriptions have been used commonly in treatment of several human diseases for thousands of years in China. Huang qin, the dried root of Scutellaria baicalensis Georgi, has been used as a tocolytic agent and prescribed by Chinese medical doctors to treatment the contractive disorders in pregnant women. However, the scientific action mechanism of Huang Qin is undefined. Our preliminary data indicated that aqueous crude extract of Huang Qin exerted the significant relaxation on spontaneous constriction in 10-day pregnant rat uterus smooth muscle and IC50 values are 4.98 + 1.12 mg/ml. Therefore, studying the tocolytic activity of Huang Qin and its active components are involved in this study. Four major components including Baicalin, Baicalein, Oroxylin A, Wogonin, were isolated from Huang Qin and detected their effects on uterine contraction by in vitro tissue bath experiments. The results showed that all these four compounds performed dose-dependent relaxative effects on uterine strips precontracted by acetylcholine ( 10-6 M ), PGF2a ( 10-7 M ) and oxytocin ( 10-3 U/ml ). However, in KCl-induced contraction in uterus, Baicalein and Oroxylin A induced uterine relaxation was suppressed apparently, compared with the data of oxytocin-treated uterus, but no obvious inhibition on Baicalin and Wogonin induced relaxation. This result indicated that potassium channels and membranne potential might be involved in Baicalein and Oroxylin A induced uterine relaxation. Pharmacological studies using potassium channel antagonists such as tetraethylammonium ( TEA; 1 and 10 mM ), 4-aminopyridine ( 4-AP ; 5 mM ), glipizide ( 30μM ) were performed to demonstrate the role of potassium channels in uterine relaxation induced by these four compounds. The results showed that TEA, 4-AP and glipizise effectively block Baicalein and Oroxylin A induced uterine relaxation, but not in Baicalin and Wogonin induced relaxation. As the same part of experiment, Baicalin and Wogonin induced relaxation were attenuated byβ-receptor blocker ( Propranolol ; 10-5 M ), cyclooxyngase inhibitor ( Indomethacin ; 60 μM ). This study demonstrated that the tocolytic activity might be due to its relaxative activity components of Huang Qin and showed the effective inhibitory activities on uterine contraction. This study aims to the scientific improve Chinese herb, and the evidence suggesting the drug information of efficacy for clinic doctors. On basis of the potential pharmacological actions and active compounds isolation, a potential tocolytic agent will develop in the future.

中文摘要……………………………………………………………….1
英文摘要……………………………………………………………….3
序論…………………………………………………………………….5
第一部份：黃芩及其主成分安胎活性評估
Ⅰ 前言……………………………………………………………..7
Ⅱ 實驗材料
1藥材……………………………………………………………8
2動物……………………………………………………….…..8
3儀器…………………………………………………….……..8
4試藥…………………………………………………………...9
Ⅲ 實驗方法
1實驗中藥材抽取與檢測藥物之製備………………………..10
2生理液之組成與製備………………………………………..10
3游離子宮平滑肌之製備……………………………………10
4子宮平滑肌自發收縮之活性評估…………………………11
5 黃芩及其主成分對懷孕之自發性收縮作用……………..11
Ⅳ 結果
1黃芩水抽取物對懷孕之自發性收縮作用…………………12
2黃芩之主成分對懷孕自發性收縮之作用………………...12
Ⅴ 討論….…………………………………………………………13
第一部份：黃芩主成分之安胎作用機制研究
Ⅰ 前言…………………………………………………………….14
Ⅱ 實驗材料
1藥物…………………………………………………………..22
2動物…………………………………………………………..22
3儀器…………………………………………………………..22
4試藥…………………………………………………………..23
Ⅲ 實驗方法
1藥物之製備………………………………………………….24
2生理液之組成與製備………………………………………..24
3游離子宮平滑肌之製備……………………………………..25
4藥物對acetylcholine、PGF2α、oxytocin誘導
子宮平滑肌收縮之活性測定……………………………....25
5 藥物對acetylcholine、PGF2α、oxytocin之受
體活性測定…………………………………………………26
6藥物對子宮平滑肌鈣離子釋放之活性測定……………….26
7 藥物對鉀離子去極化之活性測定…………………………27
8藥物對鉀離子通道開啟之敏感試驗……………………….27
9藥物對Propranolol誘發收縮之活性測定…………………27
10藥物對Indomethacin誘發收縮之活性測定……………...28
11藥物對LNNA誘發收縮之活性測定……………………..28
Ⅳ、結果
1對誘縮劑- acetylcholine、PGF2α、oxytocin
誘發收縮之抑制作用……………………………………29
2對誘縮劑活化子宮收縮之影響…………………………....30
3平滑肌誘發鈣離子釋放之影響……………………………30
4對鉀離子去極化之作用……………………………………31
5對鉀離子通道開啟之活性…………………………………32
6對Propranolol誘發收縮之抑制作用……………………...33
7對Indomethacin誘發收縮之抑制作用……………………33
8對LNNA誘發收縮之抑制作用…………………………...34
Ⅴ討論………………………………………………………………35
Ⅵ 總結…..…………………………………………………………39
Ⅶ 參考文獻……………………………………………………….40

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