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1.郑州卫生健康职业学院妇儿教研室, 河南 荥阳 450199
2.郑州大桥医院妇产科,郑州 450053
3.河南中医药大学第一附属医院妇产科,郑州 450003
Published:30 June 2024,
Received:08 November 2023,
Revised:22 March 2024,
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李三阳,金蓬勃,王秋红等.大豆异黄酮对先兆流产模型大鼠的保胎作用及机制研究 Δ[J].中国药房,2024,35(12):1482-1488.
LI Sanyang,JIN Pengbo,WANG Qiuhong,et al.Study on the protective effect and mechanism of soybean isoflavones against threatened miscarriage model rats[J].ZHONGGUO YAOFANG,2024,35(12):1482-1488.
李三阳,金蓬勃,王秋红等.大豆异黄酮对先兆流产模型大鼠的保胎作用及机制研究 Δ[J].中国药房,2024,35(12):1482-1488. DOI: 10.6039/j.issn.1001-0408.2024.12.12.
LI Sanyang,JIN Pengbo,WANG Qiuhong,et al.Study on the protective effect and mechanism of soybean isoflavones against threatened miscarriage model rats[J].ZHONGGUO YAOFANG,2024,35(12):1482-1488. DOI: 10.6039/j.issn.1001-0408.2024.12.12.
目的
2
研究大豆异黄酮对先兆流产大鼠的保胎作用及可能机制。
方法
2
取雌鼠促情,与雄鼠交配、妊娠后随机分为正常组(纯化水灌胃,
n
=10)、模型组(纯化水灌胃,
n
=9)、阳性对照药组(黄体酮4 mg/kg,肌内注射,
n
=9)和大豆异黄酮低、中、高剂量组(25、50、100 mg/kg灌胃,
n
=10)。除正常组外,其余各组大鼠均于孕8 d以米非司酮+米索前列醇灌胃建立先兆流产模型。各组大鼠分别于孕1~7 d、孕9~12 d给药/纯化水,每天1次。孕14 d时,计算各组大鼠的保胎率,检测大鼠血清中
β
-人绒毛膜促性腺激素(
β
-HCG)、孕酮(P)水平,观察大鼠胎盘与蜕膜组织病理形态学变化并检测其细胞凋亡指数,检测胎盘组织中凋亡相关因子(Fas)、凋亡相关因子配体(FasL)、增殖细胞核抗原(PCNA)和肝素结合表皮生长因子(HB-EGF) mRNA及其蛋白表达,检测蜕膜组织中Fas、PCNA和HB-EGF mRNA及其蛋白表达。
结果
2
模型组大鼠胎盘组织充血扩张明显,血管较少且形态不规则,可见大量严重基质水肿、炎症细胞浸润和铁胆黄素沉积。与模型组比较,大豆异黄酮各剂量组大鼠的保胎率,血清
β
-HCG、P水平,胎盘与蜕膜组织中PCNA、HB-EGF mRNA及其蛋白表达水平均显著升高(
P
<0.05),病理学变化显著改善;胎盘与蜕膜组织细胞凋亡指数,胎盘组织中Fas、FasL mRNA及其蛋白表达水平,蜕膜组织中Fas mRNA及其蛋白表达水平均显著降低(
P
<0.05),且大豆异黄酮的上述作用呈剂量依赖性(
P
<0.05)。
结论
2
大豆异黄酮对先兆流产模型大鼠有保胎作用;其作用机制可能与下调母-胎界面Fas、FasL mRNA及其蛋白表达,上调PCNA、HB-EGF mRNA及其蛋白表达有关。
OBJECTIVE
2
To study the protective effect and possible mechanism of soybean isoflavones against threatened miscarriage rats.
METHODS
2
Female mice were selected to promote estrus and mate with male mice. After pregnancy, they were randomly divided into normal group (purified water, i.g.,
n
=10), model group (purified water, i.g.,
n
=9), positive control drug group (progesterone 4 mg/kg, i.m.,
n
=9), low-, medium- and high-dose soybean isoflavone group
s (25, 50 and 100 mg/kg, i.g.,
n
=10). Except for the normal group, the rest were given mifepristone+misoprostol on the 8th day of pregnancy to establish threatened miscarriage model, and then given purified water or drugs, once a day, on days 1-7 and 9-12 of pregnancy, respectively. At 14 days of pregnancy, the rates of fetal protection were counted. Serum levels of
β
-human chorionic gonadotrophin (
β
-HCG) and progesterone (P) in rats were detected. Pathological and morphological changes in rat placenta and decidua tissues were observed, and the apoptosis indexes of cells were detected; mRNA and protein expressions of factor of apoptosis related (Fas), factor of apoptosis related ligand (FasL), proliferating cell nuclear antigen (PCNA) and heparin binding epidermal growth factor (HB-EGF) were determined in placenta tissues, and mRNA and protein expressions of Fas, PCNA and HB-EGF in decidua tissues were detected.
RESULTS
2
In the model group, the placental tissues of rats were hyperemia and dilatation, with fewer and irregular blood vessels; severe stromal edema, inflammatory cell infiltration and iron-choledrin deposition were observed. Compared with model group, the fetal survival rates, serum levels of
β
-HCG and P, the expressions of PCNA and HB-EGF mRNA and proteins in the placenta and decidua tissue of soybean isoflavone groups increased significantly (
P
<0.05), while pathological changes were improved significantly; cell apoptosis index in the placenta and decidua tissue, the expressions of Fas, FasL mRNA and proteins in the placenta and Fas mRNA and protein in the decidua tissue decreased significantly (
P
<0.05). The effect of soybean isoflavones was dose-dependent (
P
<0.05).
CONCLUSIONS
2
Soybean isoflavone has protective effect on threatened miscarriage, the mechanism of which is related to down-regulating the expressions of Fas and FasL mRNA and protein at the maternal-fetal interface, and up-regulating the expressions of mRNA and protein of PCNA and HB-EGF.
大豆异黄酮先兆流产母-胎界面凋亡相关因子凋亡相关因子配体增殖细胞核抗原肝素结合表皮生长因子
threatened miscarriagematernal-fetal interfacefactor of apoptosis relatedfactor of apoptosis related ligandproliferating cell nuclear antigenheparin binding epidermal growth factor
尹建蓝,陈慧. 卵巢储备功能降低与自然流产[J]. 中国计划生育和妇产科,2022,14(6):20-22.
YIN J L,CHEN H. Diminished ovarian reserve and spontaneous abortion[J]. Chin J Fam Plan Gynecotokology,2022,14(6):20-22.
ZHAO H Q,HE W,YANG Z. A pairwise and network meta-analysis comparing the efficacy and safety of progestogens in threatened abortion[J]. Int J Gynaecol Obstet,2022,156(3):383-393.
ZENG P F,ZHOU H,GUO P,et al. Efficacy and safety of traditional Chinese herbal medicine in the treatment of threatened abortion:a protocol for systematic review and meta-analysis[J]. Medicine,2021,100(5):e23288.
KARACA I,ERDOĞAN Ş V,DOĞAN K,et al. The effects of exogenous oral micronized progesterone on first trimester aneuploidy screening markers in women with threatened miscarriage:a matched case control study[J]. J Matern Fetal Neonatal Med,2022,35(7):1224-1229.
王文祥,蔡淑凤,张文昌. 大豆异黄酮持续暴露对小鼠卵巢发育影响[J]. 中国公共卫生,2015,31(5):597-599.
WANG W X,CAI S F,ZHANG W C. Effects of conti-nuous soy isoflavones exposure on ovarian development in mice[J]. Chin J Public Health,2015,31(5):597-599.
陈益钦,管芳圆,申琪,等. 大豆异黄酮对成年期大鼠卵巢卵泡发育的影响[J]. 环境与职业医学,2019,36(9):812-817.
CHEN Y Q,GUAN F Y,SHEN Q,et al. Effects of soy isoflavone on ovarian follicle development in adult rats[J]. J Environ Occup Med,2019,36(9):812-817.
陈浩瀚,王锦湘,王敏奇. 大豆异黄酮对生长猪生长性能、血清生化、免疫和抗氧化能力的影响[J]. 中国畜牧杂志,2022,58(5):229-233,238.
CHEN H H,WANG J X,WANG M Q. Effects of dietary supplementation of soybean isoflavones on growth performance,serum biochemistry,immunity and antioxidant capacity in growing pigs[J]. Chin J Anim Sci,2022,58(5):229-233,238.
张曼. 大豆衍生的植物雌激素调节牛发情期和怀孕早期中的子宫内膜前列腺素的分泌[J]. 国外医药(植物药分册),2006,21(2):79-80.
ZHANG M. Soybean-derived phytoestrogens regulate the secretion of prostaglandin in bovine endometrium during estrus and early pregnancy[J]. World Phytomedicines,2006,21(2):79-80.
张堃,吕向坤,焦艾丽,等. JAK2/STAT3通路槲皮素对先兆流产大鼠的保胎作用及对激素水平的影响[J]. 武警医学,2021,32(11):963-968.
ZHANG K,LV X K,JIAO A L,et al. Effect of quercetin on anti-abortion and hormone levels in threatened abortion in rats based on JAK2/STAT3 pathway[J]. Med J Chin People’s Armed Police Force,2021,32(11):963-968.
戴仕林,陈蓉,胥京生,等. 培土孕康汤防治大鼠先兆流产的作用[J].中国实验方剂学杂志,2010,16(16):113-115.
DAI S L,CHEN R,XU J S,et al. Effect of Peitu yunkang decoction on threatened abortion in rats[J]. Chin J Exp Tradit Med Formulae,2010,16(16):113-115.
游祥,王金玲,马晓宇,等. 中药复方方剂对先兆流产大鼠妊娠结局及PGF2α、PPAP-A的影响[J]. 中兽医医药杂志,2018,37(6):5-8.
YOU X,WANG J L,MA X Y,et al. Effects of compound traditional Chinese medicine on PGF2α and PAPP-a level in rats with threatened abortion[J]. J Tradit Chin Vet Med,2018,37(6):5-8.
王培培. 益气补肾方联合黄体酮对肾虚型先兆流产保胎率及对血绒毛膜促性腺激素、孕酮、雌二醇的影响[J]. 四川中医,2022,40(3):176-178.
WANG P P. Effects of Yiqi bushen recipe combined with progesterone on pregnancy retention rate of threatened abortion with kidney deficiency and on serum gonadotropin,progesterone and estradiol[J]. J Sichuan Tradit Chin Med,2022,40(3):176-178.
陈海英,孟涛. oxLDL和大豆异黄酮对滋养细胞LOX-1表达的调控及意义[J]. 中国医科大学学报,2008,37(4):465-467.
CHEN H Y,MENG T. The regulation of oxLDL and soybean isoflavones on expression of LOX-1 in trophoblast cells and its significance[J]. J China Med Univ,2008,37(4):465-467.
OZMEN A,KIPMEN-KORGUN D,ISENLIK B S,et al. Does fresh or frozen embryo transfer affect imprinted gene expressions in human term placenta?[J]. Acta Histochem,2021,123(3):151694.
LAI K M,GOH B H,LEE W L. Attenuating influenza a virus infection by heparin binding EGF-like growth factor[J]. Growth Factors,2020,38(3/4):167-176.
SONG Z Y,TIAN X Y,SHI Q Y. Fas,caspase-8,and caspase-9 pathway-mediated bile acid-induced fetal cardiomyocyte apoptosis in intrahepatic cholestasis pregnant rat models[J]. J Obstet Gynaecol Res,2021,47(7):2298-2306.
ZHAI J L,XIAO Z Y,WANG Y M,et al. Human embryo-nic development:from peri-implantation to gastrulation[J]. Trends Cell Biol,2022,32(1):18-29.
田洪成,马鹤, 张向卉, 等. 表皮-钙黏蛋白、增殖细胞核抗原在来曲唑诱导大鼠多囊卵巢综合征模型卵巢中的表达[J]. 实用妇产科杂志, 2023, 39(3): 217-220.
TIAN H C, MA H, ZHANG X H, et al. Expression of E-cadherin and PCNA in letrozole-induced polycystic ovary syndrome in rats[J]. J Pract Obstet Gynecol, 2023, 39(3): 217-220.
ZHOU L, ZHOU W Q, JOSEPH A M, et al. Group 3 innate lymphoid cells produce the growth factor HB-EGF to protect the intestine from TNF-mediated inflammation[J]. Nat Immunol, 2022, 23(2): 251-261.
马红霞, 尤昭玲,王小云.菟丝子总黄酮对大鼠流产模型母-胎界面Fas/FasL、PCNA、HB-EGF表达的影响[J].中药材, 2008, 31(11): 1706-1709.
MA H X, YOU Z L, WANG X Y. Effect of total flavones from Cuscuta chinensis on expression of Fas/FasL, PCNA and HB-EGF in SD rats model with bromocriptine-induced abortion[J]. J Chin Med Mater, 2008, 31(11): 1706-1709.
YU J,LUO Y,YANG XF,et al. Effects of perinatal exposure to nonylphenol on delivery outcomes of pregnant rats and inflammatory hepatic injury in newborn rats[J]. Braz J Med Biol Res,2016,49(12):e5647.
OZBILGIN K,KARACA F,TURAN A,et al. The higher heparin-binding epidermal growth factor(HB-EGF)in missed abortion[J]. Taiwan J Obstet Gynecol,2015,54(1):13-18.
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