长期吸入低浓度七氟醚孕鼠子宫内膜细胞间黏附分子1及基质金属蛋白酶9的表达  

Expression of intercellular cell adhesion molecule 1 and matrix metalloproteinase 9 in endometrium of pregnant mice with long-term exposure to low concentration of sevoflurane

作　　者：舒蕤 张成明[2] 张如意[1] 刘金倩 宋立娟 静广建 于飞 Shu Rui;Zhang Chengming;Zhang Ruyi;Liu Jinqian;Song Lijuan;Jing Guangjian;Yu Fei(Department of Anesthesiology,Affiliated Hospital of Binzhou Medical University,Binzhou 256603,Shandong Province,China;Weifang Medical University,Weifang 261042,Shandong Province,China)

机构地区：[1]滨州医学院附属医院麻醉科,山东省滨州市256603 [2]潍坊医学院,山东省潍坊市261042

出　　处：《中国组织工程研究》2023年第28期4456-4461,共6页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金(81900269),项目负责人:于飞;滨州医学院“临床+X”项目(BY2021LCX28),项目负责人:静广建。

摘　　要：背景:流行病学研究显示,长期吸入七氟醚废气的女性工作者其生育能力降低,流产及胎儿畸形的发生率增高。目的:模拟长期暴露于七氟醚废气的工作坏境,通过观察低浓度七氟醚染毒孕鼠子宫内膜细胞间黏附分子1、整合素β1、P-选择素、基质金属蛋白酶9的表达,来探讨低浓度七氟醚染毒致胚胎植入障碍机制。拟为临床安全用药、职业防护提供依据,为下一步从基因水平、分子水平研究吸入麻醉药物对胚胎着床影响的机制奠定基础。方法:雌性昆明小鼠40只,雄性昆明小鼠16只,6周龄,体质量(20±2)g,分笼饲养。40只雌鼠随机分为2组,实验组每天持续吸入0.1%七氟醚6 h,对照组正常饲养。30 d后取发情期雌鼠与性成熟雄鼠2∶1合笼,合笼第2日晨7:00观察雌鼠是否受孕。受孕雌鼠维持原条件饲养(每组受孕小鼠n≥8)。孕4.5d取子宫制作组织切片,经过免疫组化染色,分析并统计子宫内膜组织中细胞间黏附分子1、整合素β1、P-选择素、基质金属蛋白酶9的表达,并计算阳性反应物的平均积分吸光度值。结果与结论:(1)实验组、对照组分别有17,15只雌鼠先后进入发情期;合笼后两组分别有12,10只雌鼠发现阴栓;孕4.5 d解剖发现,两组分别有5,2只雌鼠为假孕,故实验组、对照组分别有7,8只雌鼠怀孕,实验组空缺数值用本组平均值代替,进行后续对照实验;(2)免疫组化结果显示,所有孕鼠子宫内膜(腺上皮细胞、腔上皮细胞及基质细胞)均有棕黄色阳性着色,但实验组孕鼠子宫内膜细胞间黏附分子1、整合素β1、P-选择素、基质金属蛋白酶9的阳性表达(0.019±0.007,0.017±0.007,0.015±0.005,0.012±0.005)分别低于对应对照组(0.032±0.014,0.025±0.008,0.021±0.007,0.023±0.005),差异有显著性意义(P<0.05);(3)提示长期吸入0.1%七氟醚影响小鼠胚胎与子宫内膜的黏附及胚胎着床,可能与七氟醚通过抑制子宫内膜细胞间黏附分子1BACKGROUND:Epidemiological studies have found that female workers who are exposed to waste sevoflurane for a long time have reduced fertility and increased incidence of abortion and fetal deformity.OBJECTIVE:To imitate the working environment of long-term exposure to waste sevoflurane and investigate the mechanism of embryo implantation disorder induced by low-concentration sevoflurane exposure by observing the expression of intercellular adhesion molecule 1,integrin β1,P-selectin,and matrix metalloproteinase 9 in endometrium of pregnant mice exposed to low concentrations of sevoflurane,atiempting to provide a basis for clinical safe drug use and occupational protection and to lay a foundation for further research on the mechanism of inhalation anesthetics on embryo implantation at gene and molecular levels.METHODS:Forty female Kunming mice and sixteen male Kunming mice,aged 6 weeks,weighting(20±2)g,were caged separately.Forty female mice were randomly divided into experimental group and control group.Mice in the experimental group were exposed to 0.1%sevoflurane,6 hours per day,while those in the control group were exposed to the air.Thirty days later,the female mice in estrus were caged with mature male mice at a rate of 2:1.Whether the female mice were pregnant was observed at 7:00 am on the second day after mating.The pregnant mice were kept independently in the original condition(n≥8 pregnant mice in each group).Mouse uterus on day 4.5 of gestation was removed and sliced for histological observation.The expression of intercellular adhesion molecule 1,integrin β1,P-selectin,and matrix metalloproteinase 9 in endometrial tissue was detected by immunohistochemistry and statistically analyzed.The average integrated absorbance value of positive reactants was calculated.RESULTS AND CONCLUSION:In the experimental and control groups,17 and 15 female mice were respectively found in estrus;12 and 10 female mice respectively were found vaginal plugs after mating.Five and two female mice were found pseudopregnant on

关 键 词：七氟醚 细胞间黏附分子1 整合素Β1 P-选择素 基质金属蛋白酶9 

分 类 号：R459.9[医药卫生—治疗学] R318[医药卫生—临床医学] R135