Experimental Study Of Therapy Medicine For Endometriosis

Objective:To investigate the therapy effects of ER-antagonists（ER-A）,PR-antagonists（PR-A）and Sanjie Zhentong Capsule（SJZTC）to the endometriosis（EMs）model,to provide the new medicine for the clinical therapy of EMs.Methods:1.Eutopic endometrium of women with endometriosis was transplanted to the severe combined immunodeficiency disease（SCID）mice,and the mice randomized into treatment groups and control group.Two weeks after the transplantation,the treatment groups were injected into the subcutaneously of the back with Faslodex（5mg/kg/d）,Mifepristone（30mg/kg/d）.The control group was given equivalent volume dissolvent（50ul/d）,the treatment lasted four weeks.The endometriotic lesions were excised and weighed.We used immunohistochemistry to determined the expression of ER、PR and Ki-67 to value the treating effect.2.By means of vaginal smear the cycle of the mice were determined,the autografting EMs model of Balb/c were established in estrus cycle stage,and the mice randomized into treatment groups and control group.Two weeks later,the implant volumes were measured by performing a second laparotomy,one day after the second look the treatment groups were injected into the subcutaneously of the back with ZK191703（1mg/kg/d）,ZK230211（10mg/kg/d）and ZK31618（1mg/kg/d）,The control group was given equivalent volume dissolvent（50ul/d）,the treatment lasted four weeks.At the end of administration,a third laparotomy was performed to remeasure implant volumes and the expression of ER、PR and Ki-67 were determined by immunohistochemistry,uterus and overy were obtained and weighed.3.Used vaginal smear to determined the cycle of the rat,the autografting EMs model of Lewis rat were established in estrus cycle stage,and the rat randomized into treatment groups and control group.Four weeks later,the implant volumes were measured by performing a second laparotomy,one day after the second look the treatment groups were intragastric administration of high dose SJZTC（172.8mg/day）,middle dose SJZTC（86.4mg/day）,low dose SJZTC（43.2mg/day）and Danazole（7.2mg/day）,the control group was given the normal soldium（NS）（1ml/day）.The treatment lasted four weeks.At the end of administration,a third laparotomy was performed to remeasure implant volumes and the expression of VEGF、TNFa、PCNA and TUNEL were determined by immunohistochemistry,blood and peritoneal fluid samples were obtained to test the levels of PGE2..Results:The SCID mouse model of endometriosis with subcutaneous inoculation can provide high survival rate of implantation and convenient observation.The difference were not statistically significant for the decreased weight of endometriotic lesion after treatment with the Faslodex and Mifepristone compared with the control group（P>0.05）.The weight of uterus were statistically significant lighter of the faslodex treated group compared with the mifepristone treated group and control group（P ﹤ 0.01）.The expression of ERa and Ki-67 statistically significant reduced in lesions from mice treated with faslodex compared with the control group（P﹤0.01）.The expression of PR and Ki-67 statistically significant reduced in lesions from mice treated with mifepristone compared with the control group（P﹤0.01）.2.In the experiment of endometriosis model of Balb/c,the volume of the focus in the peritoneum was statistically deflate of the treatment group of ZK191703 or ZK230211 or ZK31618 compared with the control group（P﹤0.01）.The weight of uterus were statistically significant lighter of the ZK191703 treated group compared with the ZK230211 or ZK31618 treated group and control group（P﹤0.01）.The expression of ERa and Ki-67 statistically significant reduced in lesions from Balb/c treated with ZK191703 compared with the control group（P﹤0.01）.The expression of PR and Ki-67 statistically significant reduced in lesions from Balb/c treated with ZK230211 compared with the control group（P ﹤ 0.01）.3.In the experiment of endometriosis model of Lewis rat,the volume of the focus in the peritoneum was statistically deflate of the treatment group of high dose SJZTC or middle dose SJZTC or low dose SJZTC or danazole compared with the control group（P﹤0.01）.The expression of VEGF or TNFa or PCNA statistically significant reduced and TUNEL statistically significant increased in lesions from rat in treatment groups compared with the control group（P﹤0.05）.The levels of PGE2 of blood and peritoneal fluid of the rat was decreased significantly in the treatment groups compared with the control group（P﹤0.05）.Conclusion:1.ER-antagonist and PR-antagonist can effective inhibit the growth of the endometriotic lesions of the mice,they are the active drug for the treatment of endometriosis.2.SJZTC can effective inhibit the growth and development of endometriosis model of Lewis rat,it is the active drug for the treatment of endometriosis.