安子合剂对ACA阳性流产小鼠母胎界面JAK/STAT3信号通路的影响

许家莹; 陆启滨

安子合剂对ACA阳性流产小鼠母胎界面JAK/STAT3信号通路的影响

南京中医药大学附属医院，江苏南京 210029

计量
- 文章访问数: 824
- HTML全文浏览量: 4
- PDF下载量: 865
- 被引次数: 0
出版历程
- 刊出日期: 2016-05-10

Influences of Anzi Heji on JAK/STAT3 Signaling Pathway on the Maternal-Fetal Interface of Mice Suffering ACA Positive Abortion

摘要

摘要: 目的观察安子合剂对抗心磷脂抗体(ACA)阳性小鼠母胎界面JAK/STAT3信号通路的影响。方法以人β2-GPⅠ为诱导剂建立ACA阳性小鼠模型，空白组给予生理盐水，模型组给予人β2-GPⅠ；各治疗组分别给予阿司匹林和高、低两种不同剂量安子合剂，于妊娠第15天处死，计算胚胎吸收率，采用ELISA方法检测外周血ACA；采用免疫组化方法检测胎盘、蜕膜组织JAK、GP130、p-STAT3，以Western blot方法检测STAT3、p-STAT3。结果安子合剂低、高剂量组、阿司匹林组小鼠的胚胎吸收率明显降低，小鼠血清ACA的滴度也显著降低（P<0.05)，母胎界面的JAK、GP130、p-STAT3的表达均增高，其中胎盘的JAK、p-STAT3的表达与模型组比较具有显著差异（P<0.05)，蜕膜GP130、p-STAT3的表达与模型组比较具有显著差异（P<0.05)。结论 ACA导致妊娠丢失的病理机制与母胎界面JAK/STAT3信号通路有关，安子合剂发挥治疗作用的机制可能是通过提高胎盘JAK的表达、增强蜕膜GP130的表达，促进胎盘及蜕膜STAT3的活化。
- 抗心磷脂抗体 /
- 流产 /
- JAK/STAT3信号通路 /
- 安子合剂
Abstract: OBJECTIVE It is to observe the influences of Anzi Heji on the JAK/STAT3 signaling pathways on the maternal-fetal interface of anticardiolipin antibody (ACA) positive mice. METHODS Establish ACA positive mice model with humanβ2-GPⅠ as derivant， and administer normal saline to the blank group and humanβ2-GPⅠ to the model group; administer aspirin and high and low dose Anzi Heji respectively to each therapy group， kill the mice at the 15th day of their pregnancy， calculate the embryo resorption rate， and test the ACA of peripheral blood by means of ELISA; test the JAK， GP130 and p-STAT3 of placenta and decidual tissue with immunohistochemical method， and test STAT3 and p-STAT3 with western blot method. RESULTS The embryo resorption rate of the mice of low- and high-dose Anzi Heji groups and aspirin group was lowered obviously， so was the titer of ACA in the serum of mice (P<0.05)， the expression of JAK， GP130 and p-STAT3 on the maternal-fetal interface was raised， and wherein， the expression of JAK， p-STAT3 of placenta had significant difference from that of model group (P<0.05)， and the expression of GP130 and p-STAT3 of decidual tissue had significant difference from that of the model group (P<0.05). CONCLUSION The pathomechanism for ACA to induce pregnancy loss is related to the JAK/ STAT3 signaling pathways on the maternal-fetal interface， and the mechanism for Anzi Heji to produce therapeutic effect is possibly to promote the activation of STAT3 of placenta and decidual tissue by enhancing the expression of JAK of placenta and strengthening the expression of GP130 of decidual tissue.
- anticardiolipin antibody /
- abortion /
- JAK/STAT3 signaling pathway /
- Anzi Heji

HTML全文

参考文献(21)

[1]	陆启滨．抗心磷脂抗体阳性先兆流产的病因病机探析[J]．中华中医药学刊，2008， 26（6）：1127-1129．
[2]	Lu QB. The etiopathogenisis and pathogenesis investigation of threatened abortion in pregnant women with antiphospholipid antibody positive[J]. Chin Arch Tradit Chin Med， 2008， 26(6): 1127-1129.
[3]	Murray PJ. The JAK-STAT signaling pathway: input and output integration[J]. J Immunol， 2007， 178(5): 2623-2629.
[4]	蒋树龙．JAK2/STAT3/SOCS3信号通路与肿瘤转移[J]．中国肿瘤生物治疗杂志，2014， 21（6）：698-702．
[5]	Jiang SL. JAK2/STAT3/SOCS3 signaling pathway and tumor metastasis[J]. Chin J Cancer Biother， 2014， 21(6): 698-702.
[6]	许袖，杨增明．胚胎着床过程中的STAT3调控网络[J]．中国细胞生物学学报，2011， 33（5）：570-576．
[7]	Xu X， Yang ZM. Molecular network of STAT3 during embryo implantation[J]. Chin J Cell Biol， 2011， 33(5): 570-576.
[8]	肖世金，赵爱民，鲍世民．补体过度激活与自身免疫型复发性流产的关系[J]．上海交通大学学报(医学版)，2011， 31（8）：1125-1128．
[9]	Xiao SJ， Zhao AM， Bao SM. Relationship between excessive complement activation and autoimmune-type recurrent spontaneous abortion[J]. J Shanghai Jiaotong Univ (Med Sci)， 2011， 31(8): 1125-1128.
[10]	Katzav A， Menachem A， Maggio N， et al. IgG accumulates in inhibitory hippocampal neurons of experimental antiphospholipid syndrome[J]. J Autoimmun， 2014， 55: 86-93.
[11]	Al Jameil N， Tyagi P， Al Shenefy A. Incidence of anticardiolipin antibodies and lupus anticoagulant factor among women experiencing unexplained recurrent abortion and intrauterine fetal death[J]. Int J Clin Exp Pathol， 2015， 8(3): 3204-3209.
[12]	Bose P， Black S， Kadyrov M. et al adverse effects of lupus anticoagulant positive blood sera on placental viability can be prevented by heparin in vitro[J]. Am J Obstet Gynecol， 2004， 191(6): 2125-2131.
[13]	Kwak-Kim J， Agcaoili MS， Aleta LA， et al. Management of women with recurrent pregnancy losses and antiphospholipid antibody syndrome[J]. Am J Reprod Immunol， 2013， 69(6): 596-607.
[14]	Mulla MJ， Myrtolli K， Brosens JJ， et al. Antiphospholipid antibodies limit trophoblast migration by reducing IL-6 production and STAT3 activity[J]. Am J Reprod Immunol， 2010， 63(5): 339-348.
[15]	Pierangeli SS， Vega-Ostertag ME， Raschi E， et al. Toll-like receptor and antiphospholipid mediated thrombosis: in vivo studies[J]. Ann Rheum Dis， 2007， 66(10): 1327-1333.
[16]	Silvia D'Ippolito， Riccardo Marana， Fiorella Di Nicuolo， et al. Effect of Low Molecular Weight Heparins (LMWHs) on antiphospholipid Antibodies (aPL)–Mediated Inhibition of Endometrial Angiogenesis[J].PLoS One， 2012，7(1)：e29660.
[17]	Stepkowski SM， Chen WH， Ross JA， et al. STAT3: an important regulator of multiple cytokine functions[J]. Transplantation， 2008， 85(10): 1372-1377.
[18]	Singh A， Jayaraman A， Hahn J. Modeling regulatory mechanisms in IL-6 signal transduction in hepatocytes[J]. Biotechnol Bioeng， 2006， 95(5): 850-862.
[19]	Sprague AH， Khalil RA. Inflammatory cytokines in vascular dysfunction and vascular disease[J]. Biochem Pharmacol， 2009， 78(6): 539-552.
[20]	陆启滨，任青玲，黄文华，等．安子合剂治疗先兆流产临床研究[J]．南京中医药大学学报，2011， 27（5）：414-417．
[21]	Lu QB， Ren QL， Huang WH， et al. Clinical evaluation of an Zi mixtures effects on treating threatened abortion[J]. J Nanjing Univ Tradit Chin Med， 2011， 27(5): 414-417.