助孕增膜方对肾虚胚胎着床障碍小鼠子宫内膜容受性及相关因子时序表达的影响  

Effect of Zhuyun Zengmo Recipe on Endometrial Receptivity and Temporal Expression of Endometrial Relevant Factors in Mice with Kidney-deficiency Type of Embryo Implantation Dysfunction

作　　者：李秀然[1] LI Xiu-Ran(Guangzhou Municipal Hospital of Traditional Chinese Medicine,Guangzhou 510130 Guangdong,China)

机构地区：[1]广州市中医医院,广东广州510130

出　　处：《广州中医药大学学报》2018年第6期1058-1065,共8页Journal of Guangzhou University of Traditional Chinese Medicine

基　　金：广东省中医药局科研项目(编号:20161204);广州市医药卫生科技项目(编号:20162A011006)

摘　　要：【目的】探讨中药助孕增膜方对肾虚胚胎着床障碍小鼠着床窗期子宫内膜胞饮突及整合素β3和骨桥蛋白时序表达的影响。【方法】复制肾虚胚胎着床障碍小鼠病证结合模型。造模成功后,将200只妊娠小鼠随机分为正常组、模型组、中药组(给予助孕增膜方灌胃,剂量为44.4 g·kg^(-1)·d^(-1))、西药组(给予戊酸雌二醇灌胃,剂量为0.02 mg·kg^(-1)·d^(-1)),每组50只。采用扫描电镜观察各组小鼠在妊娠第4天晚21∶30-22∶00时(第1时间点,T1)和妊娠第5天上午9∶30-10∶00时(第2时间点,T2)2个时间点子宫内膜表面胞饮突的表达。另在4组小鼠中,每组取5只小鼠于合笼第0、2、4、6、8天5个时间点取小鼠子宫内膜,并采用免疫组化和实时PCR检测各组小鼠着床窗期整合素β3和骨桥蛋白的蛋白表达及其mRNA的时序表达。【结果】(1)正常组T1时子宫内膜表面表达大量发育中的胞饮突,T2时则表达大量发育完全的胞饮突;模型组胞饮突表达迟滞于正常组,中药组胞饮突的表达接近于正常组。(2)着床窗期模型组整合素β3和骨桥蛋白的蛋白表达和mRNA表达水平显著低于正常组(P<0.01),中药组整合素β3和骨桥蛋白的蛋白表达和mRNA表达水平较模型组显著增加(P<0.01),接近正常组水平(P>0.05)。(3)正常组小鼠整合素β3和骨桥蛋白mRNA在围着床期子宫内膜的表达规律:合笼日表达较弱,随后逐渐增强,在妊娠第4天(小鼠胚胎植入当天)达到高峰(P<0.01),之后表达逐渐减弱,妊娠第8天仍高于非孕水平(P<0.05)。中药组、西药组及模型组小鼠整合素β3和骨桥蛋白mRNA在围着床期子宫内膜上的时序表达规律类似于正常组。【结论】整合素β3及骨桥蛋白可作为子宫内膜容受性的客观标志。中药助孕增膜方能使着床窗期肾虚胚胎着床障碍小鼠子宫内膜胞饮突的表达同步,并上调整合素β3和骨桥蛋白的表达,改善子宫内膜容受性。Objective To observe the effect of Zhuyun Zengmo Recipe（ZZR）on the expression of endometrial pinopodes and the temporal expression of integrin β3 and osteopontin in mice with kidney-deficiency type ofembryo implantation dysfunction during the implantation window. Methods A mice model with kidney-deficiencytype of embryo implantation dysfunction was established. After modeling, 200 pregnant mice were randomlydivided into normal group,model group,Chinese medicine group（intragastric administration of ZZR at the dosageof 44.4 g·kg-1·d-1）,western medicine group（intragastric administration of Progynova at the dosage of 0.02 mg·kg-1·d-1）,50 mice in each group. The expression of endometrial pinopodes at 21∶30-22∶00 on pregnancy day 4（T1）and at 9∶30-10∶00 on pregnancy day 5（T2）was determined by scanning electron microscopy. Five mice werechosen from each group on day 0,2,4,6,8 of being fed in the same cage,and then the endometrium wastaken out to detect the temporal expression of endometrial integrin β3 and osteopontin protein and mRNA byimmunohistochemistry and real-time PCR. Results（1）In the normal group,the abundant developing pinopodeseswere expressed in endometrial surface at T1,and abundant fully-developed pinopodeses were expressed at T2.Compared with the normal group,the expression of pinopodeses in the model group was retarted,while that in theZZR group was close to the normal group.（2）The protein and mRNA expression of integrin β3 and osteopontin inthe model group during the implantation window were lower than those in the normal group（P〈0.01）,while theabove indexes in the ZZR group were increased as compared with those in the model group（P〈0.01）and wereclose to the levels in the normal group（P〉0.05）.（3）The mRNA expression of integrin β3 and osteopontin in theperi-implantation endometrium of the normal group was characterized as follows：the levels were lower on non-pregnancy day, gradually rose to the peak on pregnancy day 4（the day of nidatio

关 键 词：助孕增膜方 胚胎着床障碍 整合素Β3 骨桥蛋白 胞饮突 子宫内膜容受性 疾病模型 动物 小鼠 

分 类 号：R285.5[医药卫生—中药学]