王毅;彭铭;高欣;赵宝玉;吴晨晨;

• 1:西北农林科技大学动物医学院

摘要(Abstract)：

苦马豆素是疯草主要有毒成分,抑制α-甘露糖苷酶的活性,引起N-聚糖加工过程失调。笔者课题组前期研究得出:苦马豆素致糖蛋白激素(促卵泡素和促黄体素)糖基化位点上糖链结构发生改变,引起促性腺激素功能发生改变。而苦马豆素中毒对家畜生殖激素分泌的调节机制尚不明确。苦马豆素腹腔注射对小鼠进行染毒,收集妊娠期和分娩期小鼠的血液、子宫和卵巢组织,检测糖基转移酶活性、生殖激素水平及其受体mRNA和类固醇限速酶蛋白质表达量。结果表明:在妊娠和分娩期,苦马豆素致子宫内膜固有层大量低聚糖蓄积,显著抑制N-聚糖加工过程关键糖基转移酶的活性(P<0.05);染毒组小鼠血液的生殖激素包括促卵泡素(FSH)、促黄体素(LH)、雌激素(E2)和孕酮(P4)水平显著低于对照组(P<0.05)。在整个妊娠周期,染毒组小鼠4种激素受体mRNA的表达量显著低于对照组(P<0.05)。在妊娠后期,染毒组小鼠3-β羟基类固醇脱氢酶(3-βHSD)和芳香化酶(CYP19A1)蛋白表达量显著低于对照组(P<0.05)。苦马豆素可使N-聚糖加工紊乱,引起促性腺激素分泌降低,进一步降低生殖激素受体和性类固醇激素限速酶的表达量,致使性类固醇激素分泌下降,导致生殖激素分泌紊乱,最终结果造成机体繁殖性能下降。

关键词(KeyWords)： 苦马豆素;小鼠;生殖毒性;糖蛋白激素;生殖激素;生殖激素受体;类固醇激素限速酶

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金青年基金(31302153);; 陕西省自然科学基金青年基金(2017JQ3012);; 中央高校基本科研业务费(Z109021548)

作者(Author): 王毅;彭铭;高欣;赵宝玉;吴晨晨;

Email:

DOI:

参考文献(References)：

• [1]赵宝玉，路浩，周启武，等．中国天然草地疯草生态及动物疯草中毒研究现状与防控[C]//中国畜牧兽医学会家禽生态学分会组委会．中国畜牧兽医学会家禽生态学分会学术研讨会论文集．西宁:中国畜牧兽医学会家禽生态学分会，2014:13
• [2]童德文，陈德坤，曹光荣．苦马豆素-BSA对家兔免疫原性研究[J]．西北农林科技大学学报:自然科学版，2001,29(5):11-14Tong D W,Chen D K,Cao G R. Study on immunogenicity of swainsonine-BSA[J]. Journal of Northwest SciTech University of Agriculture and Forestry:Natural Science Edition,2001,29(5):11-14(in Chinese)
• [3]陆元彪，周翰信，殷显智．海北藏族自治州草原棘豆、狼毒调查报告[J]．四川草原，1995(4):29-31
• [4] Ralphs M H,Graham D,Molyneux R J,et al. Seasonal grazing of locoweeds by cattle in northeastern New Mexico[J]. Journal of Range Management,1993,46(5):416-420
• [5]丁伯良，王建辰，薛登民，等．山羊甘肃棘豆中毒睾丸、附睾的病理学研究[J]．畜牧兽医学报，1994,25(4):368-374Ding B L,Wang J C,Xue D M,et al. A study on the pathology of Oxytropis kansuensis intoxication on testes and epididymis of goats[J]. Acta Veterinaria et Zootechnica Sinica,1994,25(4):368-374(in Chinese)
• [6]李勤凡，王建华，齐雪茹，等．山羊冰川棘豆中毒的血液学指标分析[J]．西北农林科技大学学报:自然科学版，2001,29(1):97-99Li Q F,Wang J H,Qi X R,et al. Hematological changes of Oxytropis glacialis poisoning in goats[J]. Journal of Northwest Sci-Tech University of Agriculture and Forestry:Natural Science Edition,2001,29(1):97-99(in Chinese)
• [7] Intoccia A P,Hwang B,Joseph G,et al. The metabolism of l-N-benzyl-β-methoxy-3-trifluoromethylphenethylamine hydrochloride in the rat,dog,monkey and man[J].Neuropharmacology,1972,11(6):761-775
• [8]郑明学，孔小明，刘凤翔，等．小花棘豆中毒羊乳对羔羊影响的病理学试验[J]．中国兽医科技，1993,23(5):25-26
• [9] James L F,Shupe J L,Binns W,et al. Abortive and teratogenic effects of locoweed on sheep and cattle[J].American Journal of Veterinary Research,1967,126(28):1379-1388
• [10] Richards J B,Hallford D M,Duff G C. Serum luteinizing hormone,testosterone,and thyroxine and growth responses of ram lambs fed locoweed(Oxytropis sericea)and treated with vitamin E/selenium[J]. Theriogenology,1999,52(6):1055-1066
• [11] Meher B R,Dixit A,Bousfield G R,et al. Glycosylation effects on FSH-FSHR interaction dynamics:A case study of different FSH glycoforms by molecular dynamics simulations[J]. Plos One,2015,10(9):1-23
• [12] Sevilhano T,de Carvalho R F,Oliveira N A J,et al. Molecular cloning and characterization of pirarucu(Arapaima gigas)follicle-stimulating hormone and luteinizing hormoneβ-subunit c DNAs[J]. Plos One,2017,12(8):1-22
• [13]荣杰．甘肃棘豆对大鼠亚急性毒性及α-甘露糖苷酶分布与表达的影响[D]．杨凌:西北农林科技大学，2011:15
• [14]王帅，权海云，任祯慧，等．自噬在疯草中毒中的作用及其机制[J]．中国兽医学报，2017,37(9):1802-1806Wang S,Quan H Y,Ren Z H,et al. Effect and mechanism of autophagy in locoweeds poisoning[J]. Chinese Journal of Veterinary Science,2017,37(9):1802-1806(in Chinese)
• [15]常乐，雷涛，吴宜艳．糖蛋白药理研究进展[J]．牡丹江医学院学报，2012,33(3):53-55
• [16]常亮，李晨辉，马志珺，等．糖蛋白激素研究进展[J]．生物技术进展，2015,5(1):22-28Chang L,Li C H,Ma Z J,et al. Progress on glycoprotein hormones[J]. Current Biotechnology,2015,5(1):22-28(in Chinese)
• [17] Colegate S M,Dorling P R,Huxtable C R. A spectroscopic investigation of swainsonine:Anα-mannosidase inhibitor isolated from Swainsona canescens[J]. Chemistry,1979,32:2257-2264
• [18]杨宗纯，韩俊阁，张娜，等．冬夏季节变化对雄性金黄地鼠下丘脑-垂体-性腺轴功能影响的研究[J]．世界中医药，2018,13(5):1063-1067Yang Z C,Han J G,Zhang N,et al. Study on effects of seasonal changes of winter and summer on the function of male golden hamsters hypothalamic-pituitary-gonad axis[J]. World Chinese Medicine,2018,13(5):1063-1067(in Chinese)
• [19]淡新刚．Gn IH对小鼠繁殖的调控及其分子机制和基因免疫技术研究[D]．武汉:华中农业大学，2015:13Dan X G. Regulation and molecular mechanisms of Gn IH on murine reproduction and study of genetic immunization techniques against Gn IH[D]. Wuhan:Huazhong Agricultural University,2015:13(in Chinese)
• [20] Wu C C,Liu X X,Ma F,et al. Hematological and histopathological effects of swainsonine in mouse[J]. BMC Veterinary Research,2015,3(11):16
• [21] Klinge C M,Bodenner D L,Desai D,et al. Binding of typeⅡnuclear receptors and estrogen receptor to full and half-site estrogen response elements in vitro[J].Nucleic Acids Research,1997,25(10):1903-1912
• [22] Huang Y,Li W,Zhao X,et al. Swainsonine differentially affects steroidogenesis and viability in caprine luteal cells in vitro[J]. Theriogenology,2013,80(1):41-49
• [23] Zrinyi Z,Maasz G,Zhang L W,et al. Effect of progesterone and its synthetic analogs on reproduction and embryonic development of a freshwater invertebrate model[J]. Aquatic Toxicology,2017,190:94-103
• [24]黄勤华，张超，胡万林，等．贵州黑山羊促黄体素β基因多态性及其与产羔数的关系[J]．贵州农业科学，2010,38(6):162-164Huang Q H,Zhang C,Hu W L,et al. Study on LHβgene polymorphism and relationship between LHβgene polymorphism and litter size in Guizhou block goat[J].Guizhou Agricultural Sciences,2010,38(6):162-164(in Chinese)
• [25] Blum W F,Riegelbauer G,Gupta D. Heterogeneity of rat FSH by chromatofocusing:Studies on in-vitro bioactivity of pituitary FSH forms and effect of neuraminidase treatment[J]. Journal of Endocrinology,1985,105(1):17-27
• [26]王海滨，李美铃，夏国良，等．促性腺激素对小鼠胚胎卵巢卵泡体外发育和类固醇激素分泌的作用[J]．中国兽医学报，2001,21(6):617-620Wang H B,Li M L,Xia G L,et al. Effects of gonadotrophins on the mouse fetal ovarian follicle development and steroidogenesis in vitro[J]. Chinese Journal of Veterinary Science,2001,21(6):617-620(in Chinese)
• [27]邹鹏达．LH诱导山羊卵泡膜细胞Akt磷酸化及对雄激素生成的影响[D]．杨凌:西北农林科技大学，2016:14Zou P D. Luteinizing hormone-induced Akt phosphorylation and its effect on androgen production in goat theca cells[D]. Yangling:Northwest A&F University,2016:14(in Chinese)
• [28]徐嗣亮，崔毓桂，刘嘉茵．LH调节女性雄激素生成的分子信号通路研究进展[J]．国际生殖健康/计划生育杂志，2015,34(4):328-332Xu S L,Cui Y G,Liu J Y. LH-inducing pathways in androgen biosynthesis of ovarian theca-cells[J]. Journal of International Reproductive Health/Family Planning,2015,34(4):328-332(in Chinese)
• [29] Schwarzenbach H,Manna P R,Stocco D M,et al.Stimulatory effect of progesterone on the expression of steroidogenic acute regulatory protein in MA-10 Leydig cells[J]. Biology of Reproduction,2003,68:1054-1063
• [30] Sugino N. The role of oxygen radical-mediated signaling pathways in endometrial function[J]. Placenta,2007,28(Suppl A):S133-S136
• [31] Mishra S,Chaube R. Distribution and localization of 3β-hydroxysteroid dehydrogenase(3β-HSD)in the brain and its regions of the catfish Heteropneustes fossilis[J].General and Comparative Endocrinology,2017,241:80-88
• [32] Fournet N,Weitsman S R,Zachow R J,et al. Transforming growth factor-beta inhibits ovarian 17 alphahydroxylase activity by a direct noncompetitive mechanism[J]. Endocrinology,1996,137:166-174