銀杏萃取物對雄性性行為影響之研究

Study on the Effects of Ginkgo biloba Extract (EGb 761) on Male Copulatory Behavior

葉桂鶯(Kuei-Ying Yeh)

指導教授 ： 蔡元奮

國立臺灣大學/醫學院/生理學研究所/博士(2009年)

https://doi.org/10.6342/NTU.2009.01358

摘要

臨床調查顯示銀杏萃取物(Ginkgo biloba extract)可以改善因服用抗抑鬱劑所導致的性功能障礙，隨後的研究利用雙盲試驗或三盲試驗的結果卻指出銀杏對於因服用憂鬱症藥物所引起的性功能障礙並沒有改善的作用。然而，這些結果的獲得都是根據臨床的問診或是病患本身的問卷調查，並不具客觀性。所以，銀杏是否對於雄性的性功能有所影響並不清楚。EGb 761是標準化的銀杏葉萃取物，而睪固酮與雄性性行為的表現關係密切。首先經由離體實驗我發現EGb 761可以增加大鼠睪丸細胞製造睪固酮，所以本研究繼以大鼠作為動物實驗模式，探討服用銀杏是否會影響雄性性行為的表現。本論文第一部份之實驗係探究EGb 761之處理對雄鼠性行為的影響及其相關荷爾蒙的變化。實驗結果顯示，EGb 761之處理會增加插入頻率(intromission frequency)與射精頻率(ejaculation frequency)這些用以評估性表現(sexual performance)之行為參數，但對用來評估性動機的行為參數包括騎乘潛伏期(mount latency)、插入潛伏期(intromission latency)或射精後間歇期(post-ejaculatory interval)等並不會有所影響。實驗結果也發現EGb 761之處理會減少血清的泌乳素濃度，並增加弓狀核(arcuate nucleus)多巴胺(dopamine)的含量。由於高泌乳素血症(hyperprolactinemia)會減少大鼠或小鼠性行為的表現，而多巴胺是泌乳素的抑制因子，這些結果說明EGb 761促進雄鼠性表現(特別是劑量為每公斤體重50毫克)其作用機轉可能與調控泌乳素的多巴胺系統有關。
在第二部份實驗所探討的是雄鼠的性動機與性表現兩者之關係，本實驗以EGb 761作為一實驗工具，利用伙伴偏好試驗(partner preference test)測試雄鼠性誘因動機(sexual incentive motivation)，並利用酪氨酸羥化酶(tyrosine hydroxylase, TH)免疫化學染色方法分析內側視前區(medial preoptic area)多巴胺神經元的活性。實驗結果顯示EGb 761之處理不影響雄鼠性誘因動機的表現，但增加其性表現。並且EGb 761增加內側視前區之背側區之TH免疫活性細胞的表現。EGb 761增加雄鼠性表現卻不影響其性動機推測可能是內側視前區之背側亞區多巴胺活性與性表現有關，而其腹側亞區則與性動機有關。
陰莖勃起是雄性要成功的表現交配行為所必需的一項行為反應，本論文第三部份實驗利用非接觸性勃起試驗(noncontact erection test) 探討EGb 761之處理是否會促進雄鼠的勃起反應。實驗結果顯示EGb 761之處理可增加大鼠非接觸性勃起，並且增加室旁核(paraventricular nucleus)與腹側蓋區(ventral tegmental area) TH免疫活性細胞的表現。利用高壓液相層析法發現EGb 761之處理可增加終紋床核(the bed nucleus of the stria terminalis)、依核(nucleus accumbens)與內側視前區多巴胺含量。因此，EGb 761之處理可能因增加中樞神經系統多巴胺的活性，進而增加大鼠非接觸性勃起的表現。本研究的結論是EGb 761之處理具有促進雄鼠性功能表現的作用(增加勃起反應與性表現)。

關鍵字

銀杏 ； 性表現 ； 性動機 ； 多巴胺 ； 內側視前區

並列摘要

Clinical investigation shows that extract of Ginkgo biloba leaf has a corrected effect on sexual dysfunction which induced by taking antidepressant. Subsequent studies show that Ginkgo does not correct antidepressant-induced sexual dysfunction in both double-blind or triple-blind test. However, these data obtained from the clinical interrogation or questionnaire of the patient do not have the objectivity. Whether Ginkgo influences male sexual function is not clear yet. EGb 761 is a standardized extract of dried leaves of Ginkgo biloba. It is well known that testosterone is essential for male copulatory behavior. I first demonstrated that primary Leydig cells treated with EGb 761 increased testosterone production. In the first part of the present study, the male rats were then used as an animal model to investigate whether Ginkgo biloba has influence on copulatory behavior. The purpose of the experiment was to study the effects of EGb 761 on male sexual behavior and the related hormones changes. The results showed that EGb 761 treatment increased the behavioral parameters of intromission frequency, and ejaculation frequency which used in evaluating sexual performance. Treatment with EGb 761 did not affect mount latency, intromission latency, and post-ejaculatory interval, which are commonly considered indicators of sexual motivation. In addition, treatment with EGb 761 decreased serum prolactin levels and increased tissue dopamine contents in the arcuate nucleus. Hyperprolactinemia decreases male copaultory behavior in rats and mice. Dopamine is the prolactin-inhibiting factor. These results indicate that treatment of EGb 761 (especially at the dose of 50 mg/kg) enhance the copulatory behavior of male rats and suggest that the dopaminergic system, which regulates prolactin secretion, may be involved in the facilitatory effect of EGb 761.
In the second experiment, we would like to understand the relationship between sexual performance and sexual motivation. The partner preference test was conducted to measure sexual incentive motivation, and tyrosine hydroxylase (TH) immunohistochemistry was used to assay the dopaminergic neuron activity in the medial preoptic area (MPOA). The results from the second experiment showed that EGb 761 treatment had no effect on sexual incentive motivation, but did increase copulatory performance. Also, treatment of EGb 761 increased TH immunoreactive (TH-ir) cells in the dorsal subregion of the MPOA. These findings suggest that sexual performance might be associated with dopaminergic activity in the dorsal MPOA subregion, while sexual motivation with that of the ventral subregion of the MPOA.
Penile erection is essential for successful copulation in males. Noncontact erection (NCE) test was used to reveal the effect of EGb 761 on erection in male rats. The results showed that treatment with EGb 761 increased NCE, and increased TH-ir expression in the paraventricular nucleus and ventral tegmental area. EGb 761 treatment increased the dopamine contents in the bed nucleus of the stria terminalis, nucleus accumbens, and MPOA. The results from the third experiment indicate that EGb 761 treatment increases central dopaminergic activity, and in turn, increases NCE. In conclusion, EGb 761 treatment improves male sexual function in rats.

並列關鍵字

Ginkgo ； sexual performance ； sexual motivation ； dopamine ； medial preoptic area

參考文獻

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