去甲二氢愈创木酸宫腔灌注对大鼠胚胎的影响

Effects of nordihydroguaiaretic acid by intrauterine perfusion on embryos in rat

目的探讨去甲二氢愈创木酸(nordihydroguaiaretic acid,NDGA)对大鼠早期胚胎及子宫蜕膜发育的影响,为计划生育新药研究奠定基础。方法在大鼠妊娠第1、7天(E1和E7)分别宫腔内插管灌注NDGA,观察第9天的胚胎种植数、血清孕酮值和胚胎直径及足月胎鼠的数目和体质量,检测子宫蜕膜和胎盘中内皮细胞生长因子VEGF和增殖细胞核抗原PCNA的表达,测量微血管密度(MVD)。结果E1给药后,NDGA各组灌注侧的胚胎数较对侧减少(P<0.05),胚胎直径显著减小(P<0.05),足月胎鼠数较对侧减少(P<0.05);E7给药后,胚胎直径减小(P<0.05);E1给药比在E7给药的胚胎直径减小更有显著性(P<0.01);蜕膜和胎盘中VEGF和PCNA表达显著减少,平均光密度值显著减小(P<0.01),MVD显著减少(P<0.01);血清孕酮值与对照组比较无显著性差异(P>0.05)。结论宫腔灌注NDGA对大鼠早期胚胎和蜕膜的发育有明显抑制作用,对大鼠血清孕酮值无明显影响。

Objective To investigate the effects of nordihydroguaiaretic acid （NDGA） on the embryos growth and decidualization of rat by intrauterine perfusion and to investigate the new medication for planned parenthood. Methods Fifty-six pregnant SD rats were randomly divided into NDGA-treated group （N） and PBS- treated control group （P） and blank control group （B）. By intubation, NDGA or PBS was perfused into the uterus on embryonic day 1 （E1） and day 7 （ET）. Rats were killed on E9 to calculate the number and measure the diameter of the embryos, as well as the number and weight of litters. The expression of VEGF, PCNA and FⅢRAg in deciduas and placenta were detected by immunohistoehemistry and image analysis. The serum concentration of progesterone on E9 was measured. Results In comparison with two control groups, the number and the diameter of embryos after perfusion were decreased with NDGA treatment on E1 （P 〈0. 05 ）. The number of full-term fetus was decreased （ P 〈 0. 05 ）. The diameter of embryos after perfusion with NDGA on E7 was significantly diminished （P 〈 0. 05）. The expression of VEGF, PCNA and FⅢRAg in the deciduas and placenta were all reduced （P 〈0.01 ）. The serum concentration of progesterone on E9 was not significantly different from that of control groups （ P 〉 0.05 ）. Conclusion NDGA can inhibit the growth of early embryo and interfere with the progress of decidualization obviously by intrauterine perfusion, but has little effect on the serum concentration of progesterone.