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浙江大学学报（医学版）
浙江大学学报（医学版）  2015, Vol. 44 Issue (3): 269-277    DOI: 10.3785/j.issn.1008-9292.2015.05.06
原著     
肥大细胞在雌激素介导的子宫内膜异位症中的作用机制研究
林开清, 朱丽波, 张信美, 林俊
浙江大学医学院附属妇产科医院普通妇科, 浙江 杭州 310006
Role of mast cells in estrogen-mediated experimental endometriosis in rats
LIN Kai-qing, ZHU Li-bo, ZHANG Xin-mei, LIN Jun
Department of Gynecology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China
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摘要：

目的:探讨肥大细胞在雌激素介导的大鼠子宫内膜异位症模型中的作用及相关机制。方法:取健康雌性未孕SD大鼠24只,采用自体子宫内膜移植法建立大鼠腹壁子宫内膜异位症模型,按每天肌肉注射不同剂量雌激素将大鼠随机分成3组(每组8只):大剂量组(雌激素200 μg/kg+双卵巢切除)、小剂量组(雌激素100 μg/kg+双卵巢切除)、模型对照组(仅作子宫内膜移植)。分别于造模后2周及4周后处死各组4只大鼠,采集血液和病灶组织标本,测量各组子宫内膜异位症病灶的大小,并对病灶组织进行苏木素—伊红(HE)染色观察组织形态及角蛋白和波形蛋白免疫组织化学染色以鉴定造模是否成功。用甲苯胺蓝染色法检测各组大鼠病灶组织肥大细胞总数及脱颗粒肥大细胞数,酶联免疫吸附试验测定血清肿瘤坏死因子α水平,酶免疫分析法测定血清雌二醇水平,免疫组织化学染色法检测子宫内膜异位症病灶组织类胰蛋白酶、神经生长因子的表达水平。结果:两雌激素组2周和4周时血清雌二醇水平均大于模型对照组(均P<0.05),4周时大剂量组血清肿瘤坏死因子α浓度大于模型对照组(P<0.05);两雌激素组2周和4周病灶体积均大于模型对照组(均P<0.05);无论是2周还是4周,小剂量组甲苯胺蓝染色脱颗粒/肥大细胞总数比值均高于模型对照组(均P<0.05);4周时大剂量组神经生长因子的表达大于模型对照组(P<0.05)。结论:雌激素可促进子宫内膜异位症病灶的生长,其机制可能与激活肥大细胞脱颗粒相关,而后者可能与子宫内膜异位症模型大鼠血清肿瘤坏死因子α、神经生长因子水平升高有关。
关键词： 子宫内膜异位症/病理学;  肥大细胞/病理学;  雌激素类/药理学;  雌激素类/投药和剂量;  细胞脱颗粒;  免疫组织化学;  染色与标记;  疾病模型;  动物    
Abstract:

Objective: To investigate the role of mast cells in the pathogenesis of estrogen-mediated experimental endometriosis in rats. Methods: Endometriosis model was established by transplanting autologous fragments of uterus to the inner surface of the abdominal wall in 24 unpregnant female Sprague Dawley rats. The rats were divided randomly into three groups(n=8 in each group), and were injected with different doses of estrogen: high-dose group(200 μg·kg-1·d-1), low-dose group(100 μg·kg-1·d-1) and the control group(0 μg·kg-1·d-1). The ovaries were surgically removed in high-dose and low-dose groups. Four rats were sacrificed in each group at 2 and 4 weeks after surgery. Their serum estradiol levels, size of lesions, total number of mast cells and degranulations, serum TNF-α levels, expression of tryptase and NGF in tissues were analyzed and compared among groups. Results: The mean levels of serum estradiol 2 weeks and 4 weeks after model established and serum TNF-α at 4 weeks in estrogen-treated groups were significantly higher than those in control group(all P<0.05). The mean size of endometriotic lesions in the estrogen-treated groups was also significantly larger than that in the control group 2 weeks and 4 weeks after model established(all P<0.05). Meanwhile, both at week 2 and week 4, the mean ratio of degranulation/total number of mast cells by toluidine blue staining in low-dose estrogen group was significantly higher than that in the control group(P<0.05). The expression of NGF in high-dose estrogen group was significantly higher than that in the control group at week 4(P<0.05). Conclusion: Estrogen can promote the growth of endometriotic lesions and may mediate the pathogenesis of endometriosis by activating mast cells, which may be associated with increasing TNF-α and NGF levels.
Key words: Endometriosis/pathology    Mast cells/pathology    Estrogens/pharmacology    Estrogens/administration &    dosage    Cell degranulation    Immunohistochemistry    Staining and labeling    Disease models, animal
收稿日期: 2014-12-17 出版日期: 2015-05-25
:  R711.71  
基金资助:

国家自然科学基金(81471433,81270672);浙江省自然科学基金(Y2110128);浙江省公益性技术应用研究计划(2015C33110)
通讯作者: 张信美(1964-),男,博士,主任医师,博士生导师,主要从事子宫内膜异位症和妇科内窥镜的研究;E-mail:zxm20130729@163.com;http://orcid.org/0000-0001-7122-6435     E-mail: zxm20130729@163.com
作者简介: 林开清(1974-),男,博士,副主任医师,主要从事子宫内膜异位症和子宫腺肌症微创手术的研究;E-mail:kaiqinglin2006@sina.com;http://orcid.org/0000-0003-0315-1296
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引用本文:

林开清, 朱丽波, 张信美, 林俊. 肥大细胞在雌激素介导的子宫内膜异位症中的作用机制研究[J]. 浙江大学学报（医学版）, 2015, 44(3): 269-277.

LIN Kai-qing, ZHU Li-bo, ZHANG Xin-mei, LIN Jun. Role of mast cells in estrogen-mediated experimental endometriosis in rats. Journal of ZheJiang University(Medical Science), 2015, 44(3): 269-277.

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http://www.zjujournals.com/med/CN/10.3785/j.issn.1008-9292.2015.05.06    或    http://www.zjujournals.com/med/CN/Y2015/V44/I3/269

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