人重组γ-干扰素抗生育效应及其机理研究

Studies on the antifertility effect and the mechanism of action of human recombinant interferon gamma in rabbits

本研究以新西兰品系实验兔为动物模型，观察人重组－γ干扰素（ｈｒＩＦＮ－γ）的抗生育效应并探讨其作用机理。实验结果：ｈｒＩＦＮ－γ能降低兔胚泡的着床率，对照组的着床率为８０％，ｈｒＩＦＮ－γ２．５、５．０和１０万ＩＵ３组的着床率分别为３０％、２７％和２７％。检测血清中雌二醇（Ｅ２）水平，对照组为１５７．９±３１．８ｐｍｏｌ／Ｌ，ｈｒＩＦＮ－γ各组均有降低趋势，分别为１０７．３±１９．２、１０６．３±２１．７和１０４．９±１９．８０ｐｍｏｌ／Ｌ；血清孕酮（Ｐ）水平，对照组为５０．５９±７．６２ｎｍｏｌ／Ｌ，ｈｒＩＦＮ－γ各组分别为１０．２１±３．１８、６．２３±１．６４和４．８７±０．２６ｎｍｏｌ／Ｌ。在对卵巢和子宫组织的实验病理学的系统观察发现，ｈｒＩＦＮ－γ剂量为１０万ＩＵ时，呈明显的黄体退化、子宫内膜的发育及内膜上皮和腺体的分泌均被抑制。研究表明ｈｒＩＦＮ－γ对孕兔有一定的抗生育效应，其抗孕作用的主要靶器官可能是卵巢，从而影响子宫内环境。

Objective: To investigate the antifertility effect of human recombinant interferon gamma (hrIFN γ) and its mechanism of action. Methods: In order to test the antifertility effect of hrIFN γ the New Zealand breed rabbits were used as an animal model. After the female animals were mated with male animals, in next day (Day 1) were randomly divided into 4 groups. There were control group,hrIFN γ 25 000 IU, 50 000 IU and 100 000 IU groups. Saline and hrIFN γ at different doses were administered seperately to control and experimental rabbits via vaginal muscular injection of Day 1 and were killed at Day 12 of pregnancy. The animal number of implantation and percentage of implantation were counted and calculated. The concentration of serum estriadiol and progesterone were measured in animals of each group by ELISA. In addition, the morphology of ovary and uterus of the animals in each group were surveyed by experimental pathological methods. Results: Compared control group with experimental groups, implantation of blastocyst was inhibited by various doses of hrIFN γ. Implantation percentage of animals were: control group 80%; hrIFN γ 2 500 IU 30%, hrIFN γ 50 000 IU 27%, and hrIFN γ 100 000 IU 27%. The concentrations of estriadiol and progesteron in serum decreased. The estriadiol level of control group 157.9±31.83 pmol/L, hrIFN γ 25 000 IU 107.3±19.24 pmol/L and hrIFN γ 50 000 IU 106.3±21.70 pmol/L, hrIFN γ 100 000 IU 104.9±19.80 pmol/L.The progesterone levelin serum decreased obviously,in control group 50.59±7.62 nmol/L, hrIFN γ 25 000 IU 10.21±3.18 nmol/L, hrIFN γ 50 000 IU6.23±1.64 nmol/L and hrIFN γ 100 000 IU 4.87±0.26 nmol/L. The experimental pathological systematic observation revealed that rhIFN γ at the dose of 100 000 IU/animal resulted in morphological alterations of ovarian and endomtrial tissue of the pregnant rabbits. It induced obvious luteal regresstion, inhibited endometrial development and glandular secretion. Conclusion: This study indicated that hrIFN γ exerted a certain anti contraceptive effect on the pregnant rabbit. The ovary might be the main target organ. The alternations of the ovary effected the intra uterine environment and made it unfavorable for the pregnancy.