复方阿胶浆对超促排卵小鼠子宫内膜integrinαvβ3、VEGF-A表达的影响
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摘要
目的观察复方阿胶浆对超促排卵小鼠子宫内膜中整合素αvβ3(integrinαvβ3)及血管内皮生长因子A(vascular endothelial growth factor A,VEGF-A)表达的影响,探讨复方阿胶浆对小鼠子宫内膜容受性的影响。方法将小鼠分为3组,分别为空白组、模型组、中药组。模型组及中药组应用孕马血清促性腺激素(pregnant mare serum gonadotropin,PMSG)+人绒毛膜促性腺激素(human chorionic gonadotropin,HCG)建立超促排卵小鼠模型;中药组小鼠给予复方阿胶浆灌胃,共15 d,空白组、模型组给予等量生理盐水灌胃。采用苏木精-伊红染色法(hematoxylin-eosin staining,HE)染色、免疫组织化学法对子宫进行病理切片观察;采用免疫蛋白印迹试验对integrinαvβ3、VEGF-A在子宫中的表达量进行定量分析。结果与空白组相比,模型组小鼠子宫内膜中integrinαvβ3、VEGF-A的表达明显降低,组间比较差异具有统计学意义(P<0.05)。与模型组相比,中药组小鼠子宫内膜中integrinαvβ3、VEGF-A的表达明显增多,组间比较差异具有统计学意义(P<0.05)。结论复方阿胶浆可通过调节超促排卵小鼠子宫内膜中integrinαvβ3、VEGF-A的表达,减少促排卵药物对子宫的不利影响,改善其子宫内膜容受性。
Objective To observe the effect of compound Ejiao slurry on the expressions of integrinαvβ3 and vascular endothelial growth factor A(VEGF-A) in endometrial of superovulated mice,and investigate its effect on endometrial receptivity in mice.Methods The mice were randomly divided into 3 groups,including blank group, model group and traditional Chinese medicine group.The model group and traditional Chinese medicine group were given pregnant mare serum gonadotropin(PMSG) and human chorionic gonadotropin(HCG) to establish superovulation model.The mice in traditional Chinese medicine group were treated with compound Ejiao slurry via gavage for 15 days. The blank group and model group were treated with the same amount of normal saline.The pathological sections of uterus were observed by hematoxylin-eosin staining(HE) and immunohistochemistry,and the expressions of integrinαvβ3 and VEGF-A in uterus were quantitatively analyzed by western blot.Results The expressions of integrinαvβ3 and VEGF-A in mice's endometrium of model group were significantly lower than those in blank group(P<0.05).The expression of integrinαvβ3 and VEGF-A in mice's endometrium of traditional Chinese medicine group were significantly increased than those in model group(P<0.05).Conclusion Compound Ejiao slurry can reduce the adverse effects of ovulation induction drugs on uterine growth by regulating the expressions of integrinαvβ3 and VEGF-A in endometrium of superovulated mice, and improve endometrial receptivity.
Objective To observe the effect of compound Ejiao slurry on the expressions of integrinαvβ3 and vascular endothelial growth factor A(VEGF-A) in endometrial of superovulated mice,and investigate its effect on endometrial receptivity in mice.Methods The mice were randomly divided into 3 groups,including blank group, model group and traditional Chinese medicine group.The model group and traditional Chinese medicine group were given pregnant mare serum gonadotropin(PMSG) and human chorionic gonadotropin(HCG) to establish superovulation model.The mice in traditional Chinese medicine group were treated with compound Ejiao slurry via gavage for 15 days. The blank group and model group were treated with the same amount of normal saline.The pathological sections of uterus were observed by hematoxylin-eosin staining(HE) and immunohistochemistry,and the expressions of integrinαvβ3 and VEGF-A in uterus were quantitatively analyzed by western blot.Results The expressions of integrinαvβ3 and VEGF-A in mice's endometrium of model group were significantly lower than those in blank group(P<0.05).The expression of integrinαvβ3 and VEGF-A in mice's endometrium of traditional Chinese medicine group were significantly increased than those in model group(P<0.05).Conclusion Compound Ejiao slurry can reduce the adverse effects of ovulation induction drugs on uterine growth by regulating the expressions of integrinαvβ3 and VEGF-A in endometrium of superovulated mice, and improve endometrial receptivity.
引文
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[16]Danastas K,Whittington CM,Dowland SN,et al.Ovarian Hyperstimulation Reduces Vascular Endothelial Growth Factor-ADuring Uterine Receptivity[J].Reprod Sci,2018,26(2):259-268
[17]Binder NK,Evans J,Gardner DK,et al.Endometrial signals improve embryo outcome:functional role of vascular endothelial growth factor isoforms on embryo development and implantation in mice[J].Hum Reprod,2014,29(10):2278-2286
[18]李晶晶,谈勇.复方阿胶浆对排卵障碍性不孕患者促排周期子宫内膜及卵泡发育的影响[J].现代中医药,2014,34(3):12-14,36
[19]温勤坚.阿胶对正常大鼠及超促排卵大鼠子宫内膜的作用[D].湛江:广东医学院,2009
[2]陈慧佳,甘晓玲,胡丽娜.不孕症患者心理状态及心率变异性的调查分析[J].实用妇产科杂志,2016,32(5):346-349
[3]Zhang W,Xiao X,Zhang J,et al.Clinical outcomes of frozen embryo versus fresh embryo transfer following in vitro fertilization:a meta-analysis of randomized controlled trials[J].Arch Gynecol Obstet,2018,298(2):259-272
[4]赵珂,马宗娟,李灵芝,等.补肾调轴方改善体外受精-胚胎移植失败患者子宫内膜容受性的临床疗效[J].辽宁中医杂志,2017,44(3):534-536
[5]江媚,刘雁峰,贾超敏,等.二补助育汤对反复IVF-ET失败患者子宫内膜容受性影响的临床观察[J].中华中医药杂志,2016,31(11):4875-4878
[6]苗明三.实验动物和动物实验技术[M].北京:中国中医药出版社,2003:143-144
[7]高琦,王春华,蔡霞.滋肾育胎丸对促排卵小鼠着床期子宫内膜HOXA10及下游基因整合素β3表达的影响[J].生殖医学杂志,2015,24(7):578-582
[8]Zapantis G,Szmyga MJ,Rybak EA,et al.Premature formation of nucleolar channel systems indicates advanced endometrial maturation following controlled ovarian hyperstimulation[J].Hum Reprod,2013,28(12):3292-3300
[9]李雪映,孙小然,张宏权.整合素相关微环境调控肿瘤转移[J].生物化学与生物物理进展,2017,44(8):672-677
[10]晏波,邢艳.整合素与自身免疫病[J].中华风湿病学杂志,2016,20(5):347-350
[11]杨海燕,周洁春,林文琴,等.子宫内膜整合素αvβ3表达与体外受精-胚胎移植反复种植失败的相关性研究[J].生殖医学杂志,2011,20(4):261-265
[12]Apparao KB,Murray MJ,Fritz MA,et al.Osteopontin and its receptor alphavbeta(3)integrin are coexpressed in the human endometrium during the menstrual cycle but regulated differentially[J].J Clin Endocrinol Metab,2001,86(10):4991-5000
[13]张元元,王光明.整合素αv和β3在小鼠胚胎着床中的作用[J].广东医学,2013,34(14):2147-2150
[14]Karizbodagh MP,Rashidi B,Sahebkar A,et al.Implantation Window and Angiogenesis[J].J Cell Biochem,2017,118(12):4141-4151
[15]Jee BC,Suh CS,Kim KC,et al.Expression of vascular endothelial growth factor-A and its receptor-1in a luteal endometrium in patients with repeated in vitro fertilization failure[J].Fertil Steril,2007,91(2):528-534
[16]Danastas K,Whittington CM,Dowland SN,et al.Ovarian Hyperstimulation Reduces Vascular Endothelial Growth Factor-ADuring Uterine Receptivity[J].Reprod Sci,2018,26(2):259-268
[17]Binder NK,Evans J,Gardner DK,et al.Endometrial signals improve embryo outcome:functional role of vascular endothelial growth factor isoforms on embryo development and implantation in mice[J].Hum Reprod,2014,29(10):2278-2286
[18]李晶晶,谈勇.复方阿胶浆对排卵障碍性不孕患者促排周期子宫内膜及卵泡发育的影响[J].现代中医药,2014,34(3):12-14,36
[19]温勤坚.阿胶对正常大鼠及超促排卵大鼠子宫内膜的作用[D].湛江:广东医学院,2009