目的 研究新一代青蒿素抗瘧藥物ARTPQ重復給藥對雌性大鼠生殖內(nèi)分泌的影響。方法 Wistar大鼠隨機分4組，對照組和ARTPQ低、中、高劑量組（35、70、120 mg/kg），每組15只，ig給藥14 d。給藥后每天測量大鼠動情周期，給藥結束后采集大鼠血液，Elisa方法檢測大鼠血液雌激素、腎上腺皮質(zhì)激素水平，肉眼觀察各臟器變化及稱量大鼠子宮、卵巢、腎臟及腎上腺的質(zhì)量。結果 連續(xù)給藥3 d后大鼠動情周期紊亂（維持于動情后期或間期），大鼠子宮未見有擴張，平均質(zhì)量低于對照組。ARTPQ低、中、高劑量組大鼠腎上腺系數(shù)高于對照組（P<0.05、0.01）。ARTPQ高劑量組大鼠雌激素水平低于對照組（P<0.05），而ARTPQ低、中、高劑量組大鼠腎上腺素水平高于對照組（P<0.05、0.01）。結論 ARTPQ作用于腎上腺，腎上腺增生，腎上腺皮質(zhì)激素的水平升高，雌激素水平降低，表現(xiàn)為大鼠發(fā)情周期的紊亂。

To study the ARTPQ toxicity in reproduction and endocrinology by repeated administration toxicity. Methods Wistar rats were divideded into four groups randomly, they were control and ARTPQ low-, med- and high-dose (35, 70, and 120 mg/kg) groups, which were ig administered for 14 d. Tbe estrous cycles of rats were measured daily after administration. At the end of the administration, blood was collected and measured by Elisa for the content of estrogen and cortin in rats: The changes of visceral organ were observed by eye； And uterus, ovaries, kidneys and adrenals in rats were weighed. Results The estrous cycles of rats were disordered (maintained in postestrus and anestrus) after 3 d of continuous administration, there was no expansion of the rat uterus, the average weight was lower than that in the control group. The factors of adrenal in ARTPQ low-, med-, and high-dose groups were higher than those in the control group (P <0.05, P < 0.01).The contents of estrogen in ARTPQ high-dose group were higher than those in the control group (P < 0.05), and the contents of cortin in ARTPQ low-, med-, and high-dose groups were higher than those in the control group (P < 0.05, P < 0.01). Conclusion ARTPQ acts on the adrenal glands, adrenal hyperplasia, and adrenal hormone levels rise, while estrogen levels lower, so that the rat estrous cycle disorders.

廣東省科技計劃項目（2011B010500008，2012B010300003）