Study Of Mechanism Of ZXH951 In Combination With Prostaglandin In Termination Of Early Preganancy

Roussel-Uclaf pharmaceutical factory firstly synthesised a new drug in 1982 in French. It had been called mifepritone in market. Mifepristone has the character of anti-progesterone, anti- glucocorticoid. It directly contributed to deciduas, chorionic villi, myometrium and cervix. We used it to terminate early pregnancy. With the policy of controlling population growth, our country extremely requests the medicine of anti-progesterone. Through mifepristone had characteristic of safety, effective, quick action and mini-toxicity, we pay more attention to the hemorrhage with mifepritone in the termination of early pregnancy. Zhejiang xuanju medicine company and shanghai sanhe biotechnology company manufacted a new type of progesterone receptor antagon- ZXH951. ZXH951 could substitute mifepristone if we certificated its effectiveness in termination of early pregnancy.ZXH951 had been experimented in animal experiments in the family planning research institute. The study investigated that ZXH951 effectly terminated early pregnancy of rat, mouse, rabbit and cercopithecoid. The effectiveness and toxicity with ZXH951 resembled that of mifepristone. Experiments of cercopithecoid disclosed ZXH951 could depress quantity and time of hemorrhage compared with mifepristone. If we confirm it in the clinical trial, ZXH951 maybe a new drug that was created to terminate the early pregnancy by ourselves. Throughout these researches about the effect of ZXH951 with prostaglandin on the levels of gonadal hormones in early pregnancy to compare with mifepristone, we investigated the mechanism of ZXH951 in termination of early pregnancy. At the same time, experiment firstly investigated the effect of mifepristone with prostaglandin on the levels of humoral immunity in the termination of early pregnancy for the reason that American recently reported several deaths with mifepristone and prostaglandin. The reason was related with septic shock that was caused by mifepristone. The reports hinted that the safe of mifepristone need be considered. Compared with mifepristone, we investigated the effect of ZXH951 with prostaglandin on the levels of humoral immunity in the termination of early pregnancy. All of these researches conduce to guide the use of chemical compound of progestone. safety of mifepristone should be played enough attention in the clinical use of this drug.Part I Effect of ZXH951 in combination with prostaglandin on the levels of gonadal hormones of early pregnant women in termination of early pregnancyObjective To compare with mifepristone, we investigated the effect of ZXH951 with prostaglandin on the levels of gonadal hormones in early pregnancy.Methods The levels of E2, P, T, PRL, FSH, LH andβ-HCG of peripheral blood in different days in ZXH951 or mifepristone-treated early pregnancy were determined by chemiluminescence's means.Results The levels of E2, P andβ-HCG had no obviously changes during the administration of ZXH951, then the levels of P, E2 andβ-HCG sharply decreased when the embryos were discharged at H72 and were still in the lower at H144 and H192. The levels of FSH or LH had no obviously changes during administration, then slightly rose at H144 and H192. There was no appreciable change of either PRL or T. For mifepristone, the levels of P andβ-HCG had no obviously changes during administration, E2 had increased a little, then the levels of P, E2 andβ-HCG sharply decreased at H72. that ofβ-HCG with E2 was 0.95. The levels of FSH decreased slowly during administration, then slightly rose at D6 and D8. The level of T decreased a little at D6 and D8. There was no appreciable change of either PRL or LH.Conclusion ZXH951 did not change the levels of gonadal hormone when it binded with progesterone receptor. By its effect of anti-progesterone, ZXH951 caused apomorphosis and necrosis of decidual and chorial. Thenβ-HCG decreased, soon after P and E2 decreased by corpus luteum of pregnancy atrophied.Part II Effect of ZXH951 with Prostaglandin on the Levels of Humoral Immunity of Early Pregnant Women in the Termination of the Early PregnancyObjective To investigate the effect of ZXH951 or mifepristone with prostaglandin on the function of humoral immunity in early pregnancy in the termination of early pregnancy. Methods The expressions of IgA, IgG, IgM, C3 and C4 of peripheral blood in different days in ZXH951 or mifepristone-treated early pregnancy were assessed by immunoche- mistry autoanalyser.Results With regard to ZXH951, the levels of IgA, IgG, IgM, C3 and C4 had no significant difference before treatment and after. With regard to mifepristone, the levels of IgA and IgM were lower in H72 than H0, there was significant difference (t=3.28-4.89, P< 0.05). The level of IgM was still low in D8.Conclusion ZXH951 had no obvious effect on IgA, IgG, IgM and C4. Mifepristone might affect the levels of IgA and IgM, but had no obvious effect on IgG,C3 or C4.PartⅢEffects on Decidual and Chorial Receptor by ZXH951 with Prostaglandin in the Termination of the Early PregnancyObjective To explore the changes of progesterone receptor in deciduas and chorial in the use of ZXH951 with prostaglandin in the termination of early pregnancy.Methods The decidual and chorial progesterone receptor was observed by immunohistochemistry method.Results Progesterone receptor of decidual significantly of experiment group descended. There were significant difference between the experiment group and control ( t=8.84, P<0.01).Conclusion ZXH951 could induce progesterone receptor in decidual. It maybe the mechanism of termination of the Early Pregnancy.