摘要
目的:探讨青蒿琥酯终止妊娠的机制。方法:采用RIA测定妊娠大鼠血清孕酮(P),雌二醇(E2)和肿瘤坏死因子(TNF)水平;HE染色法观察大鼠蜕膜-胎盘及卵巢的组织病理学变化,免疫组化法Ⅷ因子单克隆抗体特异性血管内皮细胞染色标记计数蜕膜-胎盘组织的微血管(MVC),血管内皮生长因子(VEGF)单克隆抗体观察胚胎和骨髓的VEGF表达;脱氧核糖核酸末端转移酶介导dUTP缺口末端标记(TUNEL)检测孕体细胞凋亡。结果:青蒿琥酯40mg/kg×5d可使妊娠大鼠血清P水平显著下降(P<0.05),E2有下降趋势,TNF则有上升趋势;MVC密度显著下降(P<0.01),蜕膜-胎盘组织和骨髓的VEGF表达显著下调(P<0.01)。由此推断,青蒿琥酯能通过下调孕体-蜕膜-胎盘复合体的微血管生成和VEGF表达,造成蜕膜-胎盘组织受损,影响蜕膜-胎盘分泌激素的功能而导致血中孕酮水平迅速下降,黄体退化和靠孕激素支持的子宫内膜进一步脱落,最后使发育中的胚胎失去血液供应和营养,胚胎发育受阻,孕体被吸收。结论:青蒿琥酯通过抑制蜕膜-胎盘组织的新生血管生成,终止妊娠。
Objective: To investigate the mechanism of artesunate in terminating early pregnancy. Methods: Serum levels of progesterone, estradiol and TNF-α were measured by RIA. The histopathological changes in the decidua-placenta and ovary of pregnant rats were observed by HE, stain. The expression of VEGF and the microvessel (VIII factor) in conceptus and marrow of conceived rats were detected by immunohistochemical staining. Apoptosis of conceptus cells was tested by means of terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL). Results: Artesunate (40 mg/kg) sc administration on day 6-10 of gestation significantly decreased the concentration of serum progesterone in early pregnant rats. E 2 tended to decrease while TNF tended to increase. Decidual cells and fetus of experimental groups were found to be degenerated on d 11. Meantime artesunate also remarkably down-regulated the expression of VEGF and lowered the microvessel density in the decidua-placenta and marrow of pregnant rats as well as of pseudo pregnant rats (P<0.01). Conclusion: Artesunate can terminate pregnancy by inhibiting angiogenesis in the decidua-placenta.
出处
《生殖与避孕》
CAS
CSCD
北大核心
2005年第6期333-339,共7页
Reproduction and Contraception
基金
中国科学院新药研究国家重点实验室
浙江省计划生育委员会资助
关键词
青蒿琥酯
蜕膜-胎盘组织
血管新生
终止妊娠
artesunate
decidua-placenta
angiogenesis
termination of early pregnancy