中藥的植物營養素對子宮鬆弛作用之開發研究-黃芩

痛經為育齡婦女常見問題，依現代醫學的病理分類上，痛經分為原發性痛經(primary dysmenorrhea)與繼發性痛經(Secondary dysmenorrhea)兩類。而原發性痛經是青春期婦女最常見婦科疾病，起因於子宮平滑肌之過度收縮、精神因素等，無特殊骨盆腔病變；原發性痛經目前有多種治療方法，以非類固醇類口服止痛劑（Nonsteroidal anti-inflammatory drugs；NSAIDs）為臨床上常用之第一線治療藥物，但伴有許多副作用。有鑑於臨床西藥治療上副作用，因此，本研究針對黃芩之植物化學成分進行藥理活性研究。黃芩(Huang Qin) 為唇形科(Labiatae) 植物Scutellaria baicalensis Georgi之乾燥根，在亞洲國家包括台灣、中國、韓國與日本廣泛應用於抗發炎、肝炎、腫瘤、抗菌與過敏，但關於痛經之應用卻無相關之科學化研究。本研究首先以現代藥理學之技術，利用大白鼠痛經模式之離體試驗，分析藥物對子宮平滑肌鬆弛作用之機制，本研究成果發現了黃芩萃取物與其成分均可抑制oxytocin, PGF2?捋PACh 所誘發之子宮平滑肌收縮。黃芩萃取物與成分baicalin與wogonin亦可抑制oxytocin在無鈣溶液所誘發之收縮然而對於baicalein與oroxylin A卻無影響；黃芩萃取物與其成分均可抑制去極化溶液所誘導子宮平滑肌收縮，因此證實黃芩造成之子宮平滑肌鬆弛與細胞外鈣離子內流及細胞內鈣離子釋放有關。另外, 對子宮平滑肌之鬆弛效應亦與鉀離子通道之開啟, 前列腺素之合成與釋放及?狳?體有關而與NO合成及α受體無關。綜合以上結果，黃芩萃取物與黃芩成分造成子宮鬆弛之機制是多重性的，我們藉離體子宮痛經模式研究，瞭解黃芩及其植物化學成分baicalin、baicalein、oroxylin A與wogonin之鬆弛效應，將其應用在治療與預防痛經疾病，進而提供臨床應用之參考。

關鍵字

原發性痛經；離體試驗；細胞外鈣離子；細胞內鈣離子；鉀離子通道

並列摘要

Dysmenorrhea, classified in primary and secondary forms, is a common problem for women of child-bearing age. Dysmenorrhea in adolescents is usually primary, and is associated with normal ovulatory cycles and with no pelvic pathology. Primary dysmenorrhea refers to menstrual cramping pain in the lower abdomen caused by enhanced uterine contractions, in the absence of underlying pelvic pathology. Dysmenorrhea is usually treated with nonsteroidal anti-inflammatory drugs in clinical medicine. Although their effect is rapid, there are many side effects. Because of these shortcomings, Chinese medicinal therapy is considered as a feasible alternative. Scutellaria baicalensis Georgi (Labiatae) is a medicinal herb widely used for the treatment of various inflammatory diseases, hepatitis, tumors, allergic reactions, and dysmenorrhea in East Asian countries including China, Korea, Taiwan, and Japan. The effect of S. baicalensis on the uterus has not yet been examined. In this research, we examined the relaxant action and the underlying physiological mechanisms of S. baicalensis and its components on the rat uterine smooth muscle. The results showed that all these S. baicalensis extracts and four constituents performed concentration-dependent relaxative effects on uterine strips precontracted by oxytocin, PGF2?? and ACh. For the uterine strips pretreated with oxytocin in Ca2+-free solution S. baicalensis extracts, baicalin and wogonin showed relaxant effect on the induced uterine contractions, but not baicalein and oroxylin A. In KCl-induced contraction in uterus, S. baicalensis extracts and four constituents induced uterine relaxation was suppressed apparently. The results showed that S. baicalensis significantly inhibited the contraction of rat uterine smooth muscle probably through the inhibition of the inflow of extracellular calcium into cells via cell membrane, and intracellular release of calcium ions. In addition, the relaxant effect induced by S. baicalensis might be due in part to the opening of K+ channels, the synthesis and release of prostaglandin and role of β receptor, but they was not influenced by NO synthase or α receptor. Our research work demonstrates multiple relaxant effects of S. baicalensis on the uterine smooth muscles. This study indicates that baicalin, baicalein, oroxylin A and wogonin are active ingredients of S. baicalensis for the treatment of primary dysmenorrhea and has the potential to be developed into an effective drug for this kind of uterine disorder.

並列關鍵字

primary dysmenorrhea ； in vitro ； extracellular calcium ； intracellular calcium ； potassium channels

參考文獻

Afifi FU, Khalil E, Abdalla (1999) Effect of isoorientin isolated from Arum palaestinum on uterine smooth muscle of rats and guinea pigs. J Ethnopharm 65:173-177.

Andersch B, Milsom I (1982) Am J Obstet Gynecol, 144:655.

Auletta FJ, Flint APE (1988) Mechanisms controlling corpus luteum function in sheep,cows,nonhuman primates,and womenespecially in relation to the time of luteolysis. Endocrine Rev, 9:88-105.

Benedoetto C (1989) Eicosanoids in primary dysmenorrhea, endometriosis and menstrual migraine. Gynecol Endocrinol, 3:71-94.

Bodelsson G, Sjoberg NO, Stjemquist M (1992) Contractile effect of endothelin in the human uterine artery and autoradiographic localization of its binding sites. Am J Obstet Gynecol, 167:745-750.

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中藥的植物營養素對子宮鬆弛作用之開發研究-黃芩

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