去甲二氢愈创木酸对大鼠卵巢功能的影响

目的探讨血管生成抑制剂去甲二氢愈创木酸(nordihydroguaiaretic acid, NDGA)对有规律动情周期大鼠卵巢功能的影响.方法将有规律动情周期的雌性大鼠按不同的动情阶段随机分为NDGA组(N)和PBS组(P),隔日皮下注射16 d,观察给药前后血清雌二醇(E2)、孕酮(P)、FSH和LH水平和给药后的交配情况及子宫和卵巢的形态学变化.结果 NDGA各组大鼠在给药后皆不能成功交配.免疫组化染色显示NDGA能显著抑制子宫内膜基质细胞增殖,减少内膜腺体数目,抑制腺上皮细胞增殖,抑制内膜血管增殖和减少微血管密度(MVD)(P<0.01).卵巢有成熟的黄体,但数目和面积比对照组显著减少,闭锁卵泡明显增多(P<0.01).血清E2显著降低,P在动情期和动情后期呈反向变化(P<0.01),FSH在动情期和动情后期明显升高(P<0.05),LH值与给药前比较没有统计学差异(P>0.05).结论长时间使用NDGA可以引起大鼠的卵巢功能紊乱.

Nordihydroguaiaretic acid causes the ovarian functional disorders in rats

Objective To investigate the effects of nordihydroguaiaretic acid (NDGA) on the ovary in rats. Methods Forty female SD rats in normal estrous cycles were randomly divided into PBS group and NDGA group, subcutaneously injected of PBS solution and 3% NDGA at the dose of 30 mg/kg respectively every other day for 16 d. The serum concentrations of follicle stimulating hormone (FSH), luteinizing hormone (LH), estrogen (E 2) and progesterone (P) were measured by chemiluminoimmunoassay before and after administration and the mating was confirmed by the occurrence of vaginal plugs and the morphological changes of uterus and ovaries were examined by immunohistochemistry after administration. Results None of the NDGA-treated rats were able to successfully mate as the absence of vaginal plugs were detected. The endometrium could maturate in all of the NDGA-treated rats, but there had a decrease not only in the number of endometrial glands, but also the proliferation rate of the glandular epithelial cells, the endometrial stroma cells, the vessels and the microvacular density (P<0.01). The number and area ratio of both mature corpus luteums and follicles were lower than those of control group, but the number of the atretic follicles had increased (P<0.01). The serum concentration of E 2 had decreased significantly (P<0.01) and P had increased in estrus and decreased in metaestrus and FSH had increased in estrus and metaestrus (P<0.05), but that of LH had no statistical difference. Conclusion The long-term treatment of NDGA may make the ovarian functional disturbance in the rats.