过刊浏览

雌激素与植物雌激素对去势鼠子宫内膜渗出的影响及机制探讨

李红芳, 段颖, 汪龙德, 田治峰, 邱小青, 张英福, 张华, 杨丽娜

兰州大学基础医学院生理学教研室；甘肃省新药临床前研究重点实验室，兰州 730000；甘肃省肿瘤医院，兰州 730050；甘肃中医学院附属医院，兰州 730020

摘要

植物雌激素属于植物衍生的非甾体化合物，可与雌激素受体结合模拟雌激素的作用，其对人类健康的潜在有益作用已成为目前国内外研究的热点。然而，植物雌激素对生殖系统的副作用研究报道较少，本文利用免疫组化和蛋白免疫印迹技术，比较17β-雌二醇(17β-estradiol, E2)、黄体酮(progesterone, P4)以及植物雌激素染料木素(genistein, Gen)、白藜芦醇(resveratrol, Res)、根皮素(phloretin, Phl)对去卵巢大鼠子宫内膜血管渗出和血管通透性的影响。以假手术大鼠为正常对照，每天分别给去势鼠皮下注射E2、E2合并P4、P4、Gen、Res或Phl，连续21 d。大鼠子宫组织HE染色显示，去势鼠皮下给予E2、 E2和P4联合处理均可诱发嗜酸性粒细胞的渗出；免疫组化和Western blot分析显示，这些去势鼠同时伴有子宫内膜VEGF、NF-κB和TNF-α表达明显上调；而Gen、Res、Phl三种植物雌激素处理后未发现子宫内膜嗜酸性粒细胞渗出及VEGF、NF-κB和TNF-α表达明显改变。结果表明：E2单独使用或E2和P4联用可通过上调VEGF、TNF-α和NF-κB的表达提高子宫内膜血管通透性，诱发去势鼠子宫内膜嗜酸性粒细胞的渗出，而同剂量的植物雌激素Gen、Res和Phl则无明显作用。

关键词： 雌激素; 植物雌激素; 血管通透性; 白细胞渗出; 血管内皮生长因子; 细胞因子

分类号：R711

Effects of estrogen and phytoestrogens on endometrial leakage in ovariectomized rats and the related mechanisms

LI Hong-Fang, UAN Ying, WANG Long-De, TIAN Zhi-Feng, QIU Xiao-Qing, ZHANG Ying-Fu, ZHANG Hua, YANG Li-Na

Department of Physiology, College of Basic Medicine； Key Laboratory of Preclinical Study for New Traditional Chinese Medicine of Gansu Province, Lanzhou University, Lanzhou 730000, China； Gansu Provincial Cancer Hospital, Lanzhou 730050, China； Affiliated Hospital, Gansu Chinese Medical College, Lanzhou 730020, China

Abstract

Phytoestrogens, a group of plant-derived non-steroidal compounds that can behave as estrogens by binding to estrogen receptors, have drawn great attention for their potentially beneficial effects on human health. However, there are few studies investigating the potential side effects of phytoestrogens on the reproductive system. The present study was to elucidate the effects of 17β-estradiol (E2), progesterone (P4), and phytoestrogens genistein (Gen), resveratrol (Res), and phloretin (Phl) on eosinophilic infiltration of the ovariectomized rat uterus and endometrial vascular permeability, and to analyze the underlying mechanisms. The ovariectomized rats received daily subcutaneous injections of E2, E2+P4, P4, Gen, Res, Phl, or an equivalent volume of vehicle for 21 days, and sham-operated animals (Sham rats) were used as the controls. Hematoxylin-eosin staining revealed a marked increase in uterine eosinophilic infiltrations in ovariectomized rats treated with E2, E2+P4 or P4, which was associated with increased expression of vascular endothelial growth factor (VEGF), nuclear factor-κB (NF-κB), and tumor necrosis factor-α (TNF-α) proteins as determined by immunohistochemical and Western blot analysis. However, all three phytoestrogens had no markedly effect on the uterine eosinophilic infiltration and the expressions of VEGF, NF-κB, and TNF-α in the uterus of ovariectomized rats. Our data demonstrate that E2 alone or in combination with P4 increases uterine eosinophilic infiltration which is related with vascular hyperpermeability caused by VEGF, NF-κB and TNF-α, whereas phytoestrogens Gen, Res, and Phl, have no such an effect.

Key words: Estrogen; phytoestrogen; capillary permeability; leukocyte leakage; vascular endothelial growth factor; cytokines

收稿日期：2012-04-24　　录用日期：2012-05-30

通讯作者：李红芳　　E-mail: lihf@lzu.edu.cn

引用本文：

李红芳, 段颖, 汪龙德, 田治峰, 邱小青, 张英福, 张华, 杨丽娜. 雌激素与植物雌激素对去势鼠子宫内膜渗出的影响及机制探讨[J]. 生理学报 2013; 65 (1): 8-18.

LI Hong-Fang, UAN Ying, WANG Long-De, TIAN Zhi-Feng, QIU Xiao-Qing, ZHANG Ying-Fu, ZHANG Hua, YANG Li-Na. Effects of estrogen and phytoestrogens on endometrial leakage in ovariectomized rats and the related mechanisms. Acta Physiol Sin 2013; 65 (1): 8-18 (in Chinese with English abstract).