罗氏内异方对子宫内膜异位症局部雌激素合成影响的实验研究

Effect of Luo's Neiyi Prescription on Estrogen Synthesis in Local Ectopic Endometrium of Endometriosis Model Rats

目的:从雌激素合成角度探讨子宫内膜异位症(简称内异症)的发病机制,以达那唑作为对照,探索罗氏内异方对内异症模型雌激素合成调节网络的影响。方法:建立大鼠内异症模型,分别给予高、低剂量罗氏内异方以及达那唑治疗,以空白模型组作对照。3周后切除异位内膜病灶,检测前列腺素E2(PGE)2、雌二醇(E)2含量和即刻早期表达基因(C-FOS)、小鸡卵白蛋白上游启动子转录因子(COUP-TF)、类固醇合成因子(SF-1)、细胞色素芳香化酶P450(P450arom)的mRNA表达水平。结果:各用药组中,中药2组的粘连程度最轻,罗氏内异方低剂量组的囊肿最小。与空白模型组比较,各用药组的大鼠异位内膜组织E2和PGE2含量均明显下降,C-FOS表达量明显减弱;2组大鼠异位内膜组织P450arom表达量明显减弱,罗氏内异方低剂量组与高剂量组、达那唑组比较则明显减弱。与其他组比较,罗氏内异方低剂量组大鼠异位内膜组织SF-1表达量明显减弱,各组间大鼠异位内膜组织COUP-TF表达量差异无显著性意义。空白模型组异位内膜的E2含量与PGE2含量、P450arom、C-FOS表达量呈显著正相关,而与COUP-TF表达量呈显著负相关;PGE2含量与P450arom表达量呈显著正相关;P450arom与SF-1表达量有显著的正相关。结论:研究证实,异位内膜局部通过SF-1-P450arom-PGE2介导雌激素合成和C-FOS对雌激素早期应答两种独立途径,使局部的E2浓聚,促进内异症发生发展。同时提示罗氏内异方在一定浓度范围内通过抑制SF-1的表达和C-FOS的表达,使局部E2含量下降,从而抑制异位内膜病灶的发展。

Objective： To reveal the pathogenic mechanism of endometriosis, and to demonstrate the effect of Luo＇s Neiyi Prescription （LNP）on regulation network of estrogen synthesis in local ectopic endometrium of endometriosis model rats. Methods： Endometrium autotransplantation method was used to establish rat models of endometriosis. The model rats except for the blank control group were administered with high-dosage LNP（LNP-H）, and low-dosage LNP （LNP-L） and Danazol, respectively. After three weeks, ectopic endometrium was taken out for the examination of the levels of estrogen （E2） and prostaglandin E2 （PGE2）, and mRNA expression levels of immediate early response gene C-FOS, chicken ovalbumin upstream promoter- transcription factor （COUP-TF）, steroid synthesis factor （SF-1）, and aromatase cytochrome P450 （P450arom）. Results： LNP groups had least endometrial adhesion, LNP-L had the smallest cyst. The contents of E2 and PGE2 as well as C-FOS expression level were lower in the medication groups than those in the blank control group. The expression of P450 arom in ectopic endometrium of LNP groups was decreased, and was lower in LNP-L group than that in LNP-H group and Danazol group. The expression of SF-1 in ectopic endometrium of LNP-L group was decreased. There was no significant difference of COUP-TF expression among the groups. In the blank control group, E2 content was positively correlated with PGE2, P450arom and C-FOS, but negatively correlated with COUP-TF. PGE2 had positive correlation with P450arom expression, and P450arom expression had positive correlation with SF-I. Conclusion.. There are two independent ways of estrogen accumulation in ectopic endometrium, the network of SF1-P450arom-PGE2, and the early response to estrogen of C-FOS, which promote the development of endometriosis. LNP in certain concentration can decrease E2 level in ectopic endometrium through inhibiting the expression of SF-1 and C-FOS.