GnRH-a反加雌激素对大鼠子宫内膜异位症模型的疗效及复发的研究  

Effect of GnRH-a combined with estrogen on endometriosis in a rat model and its recurrence

作　　者：张玲玉 刘颖蕾[1] 乔海风[1] 开海丽 刘曼华[1] 吴刘成 ZHANG Lingyu;LIU Yinglei;QIAO Haifeng;KAI Haili;LIU Manhua;WU Liucheng(The Second Affiliated Hospital of Nantong University,Nantong 226001,China;Nantong Maternal and Child Health Hospital,Nantong 226001;Experimental Animal Center of Nantong University,Nantong 226001)

机构地区：[1]南通大学第二附属医院,江苏南通226001 [2]南通市妇幼保健院,江苏南通226001 [3]南通大学实验动物中心,江苏南通226001

出　　处：《中国比较医学杂志》2018年第11期67-73,共7页Chinese Journal of Comparative Medicine

基　　金：南通市科技局重点病种的规范化临床诊疗研究(HS2014074);南通市科技计划项目(MS12017013-4)

摘　　要：目的探讨GnRH-a反加不同剂量雌激素对子宫内膜异位症的治疗效果及对复发的影响。方法将建成子宫内膜异位症模型的51只大鼠分为五组:对照组(n=10),予生理盐水1 mg/kg皮下注射,共1次;研究组:反加组Ⅰ(低剂量雌激素组n=10)、反加组Ⅱ(中剂量雌激素组n=10)、反加组Ⅲ(高剂量雌激素组n=10)、GnRH-a组(n=11)。研究组先予亮丙瑞林1 mg/kg皮下注射,共1次,反加组Ⅰ、Ⅱ、Ⅲ分别在给药第2周开始予不同剂量的戊酸雌二醇(25μg/kg、50μg/kg、100μg/kg)灌胃,同时GnRH-a组予生理盐水灌胃,3 mL/只,各研究组每天1次,共14 d。用药后第4周和7周开腹探查,测量内异灶体积,取其内异灶组织,免疫组化法检测内异灶内的TNF-α、StAR的表达,眼眶内眦静脉丛的采血法采血,酶联免疫吸附法检测血清CA125的水平。结果用药前,各组大鼠异位病灶体积比较,差异无显著性(P> 0.05)。第4周,研究组较对照组明显减小,差异有显著性(P<0.05);第7周,反加组Ⅱ、Ⅲ较反加组Ⅰ和GnRH-a组体积增大明显,差异有显著性(P<0.05)。②用药前,各组大鼠异位病灶组织中TNF-α、StAR表达,差异无显著性(P> 0.05)。第4周,研究组内异灶TNF-α、StAR表达较对照组明显降低,差异有显著性(P<0.05);反加组Ⅱ、Ⅲ较反加组Ⅰ和GnRH-a组TNF-α、StAR表达高,差异有显著性(P<0.05)。③用药前,各组大鼠血清CA125水平比较,差异无显著性(P> 0.05)。第4周,研究组血清CA125较对照组降低,差异有显著性(P<0.05)。第7周,反加组Ⅱ、Ⅲ较反加组Ⅰ和GnRH-a组血清CA125水平高,差异有显著性(P<0.05)。结论 GnRH-a反加低剂量雌激素对大鼠内异症模型有较好疗效,反向添加中、高剂量雌激素可能通过诱导TNF-α、StAR而促进大鼠子宫内膜异位症的复发。Objective To observe the therapeutic effect of a gonadotropin-releasing hormone agonist combined with various doses of estrogen in a rat model of endometriosis and the recurrence of endometriosis.Methods Fifty-one rats with endometriosis were established by autologous transplantation of the uterus and then randomly divided into five groups:control group(n=10),1 mg/kg NS subcutaneous injection once;treatment groups,add-back groupⅠ(low-dose estrogen group,n=10),add-back groupⅡ(medium-dose estrogen group,n=10),add-back groupⅢ(high-dose estrogen group,n=10),GnRH-a group(n=11),1 mg/kg leuprolide subcutaneous injection once.Add-back groupsⅠ-Ⅲwere administered various doses of estradiol valerate at week 2(25,50,and 100μg/kg)and the GnRH-a group was administered 3 mL NS per rat once a day by gavage at week 2.At weeks 3 and 6 after intragastric administration of estradiol valerate,a laparotomy was performed to measure the volume of endometriosis.The protein levels of tumor necrosis factor-α(TNF-α)and steroidogenic acute regulatory(StAR)protein were detected by immunohistochemistry.The levels of serum CA125 were detected by an enzyme-linked immunosorbent assay.Results Before the treatments,there was no significant difference in the volume of ectopic lesions in each group(P>0.05).At week 4,the mean volumes of ectopic lesions in the treatment groups were significantly reduced compared with that of the control group(P<0.05).At week 7,the volumes of ectopic lesions in add-backⅡandⅢgroups were significantly higher than those in the add-backⅠand GnRH-a groups(P<0.05).Before the treatments,there was no significant difference in the expression of TNF-αand StAR in ectopic lesions of each group(P>0.05).At week 4 of the treatments,the TNF-αand StAR expression in ectopic lesions of treatment groups was significantly lower than that in the control group(P<0.05).At week 7,TNF-αand StAR expression in add-backⅡandⅢgroups was significantly higher than that in the add-back groupⅠand GnRH-a groups(P<0.05).Before

关 键 词：大鼠子宫内膜异位症模型 促性腺激素释放激素受体激动剂 雌激素 反添加 复发 

分 类 号：R-33[医药卫生]