米非司酮对子宫内膜异位症大鼠的影响

Effect of mifepristone on endometriosis in rats

目的研究米非司酮对子宫内膜异位症(EMs)大鼠磷脂酰肌醇3-激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白(PI3K/Akt/mTOR)通路的调控作用及电子计算机断层扫描(CT)对异位病灶的评估意义。方法用自体移植法建立EMs大鼠模型,将EMs大鼠随机分为模型组及低、中、高剂量实验组,每组20只。低、中、高剂量实验组分别给予1.0,2.0,3.0 mg·kg^-1·d^-1米非司酮,灌胃,模型组灌胃等量生理盐水,连续干预4周。用CT评估异位病灶内膜厚度;用酶联免疫吸附(ELISA)法检测血清肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、雌激素(E2)、孕激素(P)水平;用蛋白质印迹(Wb)法检测异位内膜组织PI3K、Akt、mTOR蛋白的表达水平。结果模型组及低、中、高剂量实验组大鼠CT测量的异位病灶的内膜厚度分别为(3.98±1.02),(2.76±0.65),(1.88±0.52),(1.21±0.39)mm;血清TNF-α水平分别为(132.46±12.52),(92.14±8.31),(79.86±6.93),(58.64±7.32)pg·mL^-1;IL-1β水平分别为(42.86±5.13),(29.37±4.25),(21.65±3.89),(13.16±1.78)pg·mL-1;E2水平分别为(59.43±13.62),(45.56±15.23),(36.37±11.42),(29.15±6.86)pg·mL^-1。与模型组比较,低、中、高剂量实验组大鼠CT测量的异位病灶的内膜厚度,血清TNF-α、IL-1β、E2、P水平及异位内膜组织PI3K、Akt、mTOR蛋白相对表达量均降低,且呈剂量依赖性(均P<0.05)。结论米非司酮可降低EMs大鼠异位病灶的内膜厚度,调节EMs大鼠性激素水平,使异位病灶萎缩,进而控制EMs的发展,其作用机制可能与抑制PI3K/Akt/mTOR通路的信号转导相关,且CT对异位病灶具有一定的评估价值。

Objective To investigate the effect of mifepristone on the regulation of phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin protein(PI3K/Akt/mTOR)pathway in endometriosis(EMs)rats and the evaluation significance of ectopic lesions by computed tomography(CT).Methods EMs rat models were established by autotransplantation,and EMs rats were randomly divided into model group and low,medium,high dose experimental(Exp-L,Exp-M,Exp-H)groups,with 20 rats in each group.Rats in Exp-L,Exp-M,Exp-H groups were gavage with 1.0,2.0,3.0 mg·kg^-1·d^-1 mifepristone,model group was gavage with normal saline for 4 weeks.CT was used to evaluate endometrial thickness of ectopic lesions;enzyme-linked immunosorbent assay(ELISA)was used to detect serum tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),estrogen(E2)and progesterone(P)levels;Western blotting(Wb)method was used to detect the expression levels of PI3K,Akt,and mTOR proteins in ectopic endometrial tissues.Results The endometrial thickness of the ectopic lesions measured by CT in model group and Exp-L,Exp-M,Exp-H groups were(3.98±1.02),(2.76±0.65),(1.88±0.52),(1.21±0.39)mm;serum TNF-αlevels were(132.46±12.52),(92.14±8.31),(79.86±6.93)and(58.64±7.32)pg·mL-1;IL-1βlevels were(42.86±5.13),(29.37±4.25),(21.65±3.89)and(13.16±1.78)pg·mL^-1;E2 levels were(59.43±13.62),(45.56±15.23),(36.37±11.42)and(29.15±6.86)pg·mL^ -1.Compared with model group,the endometrial thickness of the ectopic lesions measured by CT,serum TNF-α,IL-1β,E2,P levels,and relative expression of PI3K,Akt,and mTOR proteins in the ectopic endometrial tissues of Exp-L,Exp-M,Exp-H groups were reduced,with dose-dependence(all P<0.05).Conclusion Mifepristone can reduce the endometrial thickness of ectopic lesions in EMs rats,regulate the level of sex hormones in EMs rats,shrink the ectopic lesions,and then control the development of EMs,and its mechanism may be related to the inhibition of the PI3K/Akt/mTOR pathway signal transduction,and CT has certain evaluation value for ectopic lesions.