【摘要】：作者前期研究發(fā)現(xiàn)佐米曲坦(ZOL)對雄性大鼠肝中CYP3A2具有誘導作用,而對雌性大鼠沒有誘導作用。闡明其機制對于研究ZOL的藥物相互作用和個體化用藥具有積極意義。由于生長激素(GH)與一些蛋白的性別差異性表達密切相關,因此,本研究探究了ZOL對大鼠GH分泌的影響,以及其對腦垂體化學損傷大鼠模型肝中CYP3A2的誘導作用。結果發(fā)現(xiàn),ZOL可以抑制正常大鼠體內血漿GH水平。與正常組大鼠的誘導結果不同,ZOL抑制了損傷組雄性大鼠肝中CYP3A2的表達。另外,ZOL對于雌雄原代肝細胞中的CYP3A1/2無明顯誘導作用。進一步研究發(fā)現(xiàn),給予ZOL后正常雄性大鼠肝中肝細胞核因子4α(HNF4α)的入核水平明顯增加,而正常雌性大鼠、腦垂體化學損傷大鼠和大鼠原代肝細胞中HNF4α的入核水平無明顯變化。結果表明,GH和HNF4α在ZOL性別差異性誘導CYP3A2的過程中發(fā)揮了重要的作用。
[Abstract]:In previous studies, we found that Zomitriptan (ZOL) could induce CYP3A2 in the liver of male rats, but not in female rats. It is of great significance to elucidate its mechanism for the study of drug interaction and individualized drug use in ZOL. Since the expression of growth hormone (GH) is closely related to the sex difference of some proteins, this study investigated the effect of ZOL on the secretion of GH in rats and on the induction of CYP3A2 in the liver of the rat model with chemical injury of pituitary gland. The results showed that ZOL could inhibit the level of plasma GH in normal rats. Different from the normal rats, ZOL inhibited the expression of CYP3A2 in the liver of the injured rats. In addition, ZOL did not induce CYP3A1/2 in primary hepatocytes of both sexes. It was found that the nucleation level of nuclear factor 4 偽 (HNF4 偽) in the liver of normal male rats was significantly increased after ZOL administration, while that of HNF4 偽 in the primary hepatocytes of normal female rats and primary hepatocytes of the normal female rats did not change significantly. The results showed that GH and HNF4 偽 played an important role in the process of inducing CYP3A2 by sex difference of ZOL.
【作者單位】： 浙江大學藥學院藥物代謝和藥物分析研究所浙江省抗腫瘤藥物研究重點實驗室;
【基金】：國家自然科學基金資助項目(30600772)
【分類號】：R965

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