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  • 王汝倩,陈露,程雯,张洁,刘璐茜,姚睿嫔,吉翔,俞超芹.内异方改善子宫内膜异位症小鼠生殖能力及作用机制[J].第二军医大学学报,2019,40(5):535-541    [点击复制]
  • WANG Ru-qian,CHEN Lu,CHENG Wen,ZHANG Jie,LIU Lu-xi,YAO Rui-pin,JI Xiang,YU Chao-qin.Neiyi recipe improving reproductive ability of mice with endometriosis and its mechanism[J].Acad J Sec Mil Med Univ,2019,40(5):535-541   [点击复制]
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内异方改善子宫内膜异位症小鼠生殖能力及作用机制
王汝倩1△,陈露1△,程雯1,张洁2,刘璐茜1,姚睿嫔1,吉翔1,俞超芹1*
0
(1. 海军军医大学(第二军医大学)长海医院中医妇科, 上海 200433;
2. 上海交通大学医学院附属第九人民医院辅助生殖科, 上海 200011
共同第一作者
*通信作者)
摘要:
目的 探讨内异方对子宫内膜异位症(EM)模型小鼠生殖能力的影响及作用机制。方法 建立EM小鼠模型,分为内异方组(n=26)、孕三烯酮组(n=25)、EM模型组(n=26)、假手术组(n=24)。连续药物干预15 d后,每组随机选择6只动情前期小鼠行卵巢组织形态学观察;剩余小鼠按雌雄比4︰1行交配实验,连续合笼15 d。观察并统计4组小鼠妊娠、内异灶、盆腔粘连、卵泡发育情况。取4组小鼠肝、肾、脾脏进行组织形态学观察。采用酶联免疫吸附试验检测小鼠腹腔液中炎性因子IL-2、IL-6和IL-10的浓度。结果 内异方组小鼠的妊娠率、内异灶体积、盆腔粘连情况较孕三烯酮组、EM模型组改善(P<0.05,P<0.01)。卵巢组织形态学观察显示内异方组卵泡发育优于孕三烯酮组、EM模型组,在改善卵泡发育方面内异方组优于孕三烯酮组(P<0.05)。与假手术组相比,EM模型组小鼠腹腔液中IL-2、IL-6水平均升高(P均<0.01),IL-10水平降低(P<0.05)。与EM模型组相比,内异方组、孕三烯酮组小鼠腹腔液中IL-2水平均下降(P<0.01),孕三烯酮组小鼠的腹腔液中IL-6水平下降(P<0.05)、IL-10水平升高(P<0.01)。孕三烯酮组小鼠妊娠率未见改善,且药物处理后体质量、肝脏和肾脏湿质量均减轻(P均<0.05),而内异方组小鼠未见明显肝、肾、脾损害。结论 内异方通过抑制内异灶的生长和减少盆腔粘连改善盆腔微环境、促进各级卵泡发育,提高了EM小鼠的生殖能力,且无不良反应,安全性好。
关键词:  子宫内膜异位症  内异方  生育力  盆腔微环境  盆腔粘连
DOI:10.16781/j.0258-879x.2019.05.0535
投稿时间:2018-11-24修订日期:2019-02-22
基金项目:国家自然科学基金(81573755,81503604,81774352),上海市中医药三年行动计划[ZY(2018-2020)-FWTX-1107],上海市妇幼健康中医专项建设项目.
Neiyi recipe improving reproductive ability of mice with endometriosis and its mechanism
WANG Ru-qian1△,CHEN Lu1△,CHENG Wen1,ZHANG Jie2,LIU Lu-xi1,YAO Rui-pin1,JI Xiang1,YU Chao-qin1*
(1. Department of Traditional Chinese Medicine(Gynecology), Changhai Hospital, Naval Medical University(Second Military Medical University), Shanghai 200433, China;
2. Department of Assisted Reproduction, Ninth People's Hospital of Shanghai, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
Co-first authors.
* Corresponding author)
Abstract:
Objective To explore the effect of Neiyi recipe on the reproductive ability of mice with endometriosis (EM) and its mechanisms. Methods The EM mouse model was established and divided into Neiyi recipe group (n=26), gestrinone group (n=25), EM model group (n=26), and sham operation group (n=24). After 15 days of continuous drug intervention, 6 proestrous mice were randomly selected from each group for histomorphological observation. The remaining mice were mated at the ratio of male to female of 4︰1 for 15 days. The pregnancy, endometriosis, pelvic adhesions and follicular development were observed and recorded in the 4 groups. The histomorphology of the liver, kidney and spleen of the mice were observed in each group. The concentrations of IL-2, IL-6 and IL-10 in peritoneal fluid of the mice were detected by enzyme-linked immunosorbent assay. Results The pregnancy rate, volume of lesions and pelvic adhesion of the mice were significantly improved in the Neiyi recipe group compared with the gestrinone group and the EM model group(P<0.05, P<0.01). The ovarian histomorphological observation showed that the follicular development of the mice was better in the Neiyi recipe group than that in the gestrinone group and the EM model group. The mice in the Neiyi recipe group had significantly better outcome in improving follicular development compared with the gestrinone group (P<0.05). Compared with the sham operation group, the levels of IL-2 and IL-6 in the peritoneal fluid of the mice were significantly increased in the EM model group (all P<0.01), and the level of IL-10 was significantly decreased (P<0.05). Compared with the EM model group, the levels of IL-2 in the peritoneal fluid of the mice were significantly decreased in the Neiyi recipe group and the gestrinone group (P<0.01), the level of IL-6 in the peritoneal fluid of the mice was significantly decreased in the gestrinone group (P<0.05) and the level of IL-10 was significantly increased (P<0.01). The pregnancy rate of the mice was not improved in the gestrinone group, and the body mass and the wet mass of liver and kidney were significantly decreased after drug treatment (all P<0.05), while the mice in the Neiyi recipe group showed no obvious damages of the liver, spleen or kidney. Conclusion Neiyi recipe can improve the pelvic microenvironment, promote follicular development and improve the reproductive ability of EM mice by inhibiting the growth of EM lesions and reducing pelvic adhesion, with no serious adverse effects and with good safety.
Key words:  endometriosis  Neiyi recipe  fertility  pelvic microenvironment  pelvic adhesi