补肾活血方对复发性流产小鼠蜕膜组织VEGF/PI3K/Akt通路表达的影响
Effect of Bushen Huoxue Formula on expression of VEGF/PI3K/Akt pathway in decidua of mice with recurrent abortion
- 上海中医药杂志 2021年55卷第2期 页码：82-89
- 作者机构：
1.上海中医药大学附属龙华医院临床研究中心（上海 200032）
2.上海中医药大学附属龙华医院妇科（上海 200032）
- 作者简介：
张婕，女，博士研究生，助理研究员，主要从事中医药防治女性生殖内分泌及肿瘤疾病的基础研究工作
李佶，主任医师，硕士研究生导师；E-mail：drliji@163.com
- 基金信息：上海市卫计委进一步加快中医药事业发展三年行动计划项目(ZY（2018-2020）-CCCX-2002-05);上海中医药大学附属龙华医院第二批专职科研人才培养计划项目(RC-2020-02-05)
DOI：10.16305/j.1007-1334.2021.2008069
中图分类号：
扫 描 看 全 文
张婕, 倪爽, 李佶. 补肾活血方对复发性流产小鼠蜕膜组织VEGF/PI3K/Akt通路表达的影响[J]. 上海中医药杂志, 2021,55(2):82-89.
Jie ZHANG, Shuang NI, Ji LI. Effect of Bushen Huoxue Formula on expression of VEGF/PI3K/Akt pathway in decidua of mice with recurrent abortion[J]. Shanghai Journal of Traditional Chinese Medicine, 2021,55(2):82-89.
张婕, 倪爽, 李佶. 补肾活血方对复发性流产小鼠蜕膜组织VEGF/PI3K/Akt通路表达的影响[J]. 上海中医药杂志, 2021,55(2):82-89. DOI： 10.16305/j.1007-1334.2021.2008069.
Jie ZHANG, Shuang NI, Ji LI. Effect of Bushen Huoxue Formula on expression of VEGF/PI3K/Akt pathway in decidua of mice with recurrent abortion[J]. Shanghai Journal of Traditional Chinese Medicine, 2021,55(2):82-89. DOI： 10.16305/j.1007-1334.2021.2008069.
摘要
目的,2,观察补肾活血方对复发性流产小鼠蜕膜组织VEGFA、VEGFR2及对PI3k/Akt信号转导通路的影响，探讨其治疗复发性流产的可能作用机制。,方法,2,建立BALB/c×CBA/J 正常妊娠小鼠模型及DBA/2×CBA/J复发性流产小鼠模型，实验随机分为正常组、模型组、黄体酮组（3.33 mg/kg）、补肾活血方低剂量组（10.47 g/kg）、补肾活血方中剂量组（20.93 g/kg）、补肾活血方高剂量组（41.87 g/kg），各组给予相应药物灌胃2周。观察各组不同浓度药物干预后CBA/J小鼠的胚胎丢失率；采用免疫组化检测小鼠蜕膜组织VEGFA、VEGFR2蛋白的表达；采用Western blot检测小鼠蜕膜组织VEGFA、VEGFR2、PI3K、Akt、p-Akt蛋白的表达。,结果,2,①与模型组比较，黄体酮组和补肾活血方低、中、高剂量组小鼠胚胎丢失率均明显下降（,P,<,0.05）。②免疫组化结果表明，与模型组比较，黄体酮组和补肾活血方中、高剂量组VEGFA蛋白阳性表达增强，黄体酮组和补肾活血方低、中、高剂量组VEGFR2蛋白阳性表达增强（,P,<,0.05）；与补肾活血方低剂量组比较，补肾活血方中、高剂量组VEGFA蛋白阳性表达增强（,P,<,0.05）。③Western blot结果表明，与模型组比较，黄体酮组和补肾活血方低、中、高剂量组VEGFA、VEGFR2、PI3K、p-Akt蛋白表达水平明显升高（,P,<,0.05）；与补肾活血方低、中剂量组比较，补肾活血方高剂量组VEGFA、VEGFR2、PI3K、p-Akt蛋白表达水平明显升高（,P,<,0.05）。,结论,2,补肾活血方能上调复发性流产模型小鼠蜕膜组织VEGFA及其受体VEGFR2的表达，其机制可能与激活PI3K/Akt信号通路相关。
Abstract
Objective,2,To observe the effect of Bushen Huoxue Formula on VEGFA, VEGFR2 and PI3K/Akt signal transduction pathway in decidua of recurrent abortion mice, and to explore the possible mechanism of Bushen Huoxue Formula in treating recurrent abortion.,Methods,2,BALB/c × CBA/J normal pregnant mice model and DBA/2 × CBA/J recurrent abortion mice model were established. The mice were randomly divided into normal group, model group, progesterone group (3.33 mg/kg), and Bushen Huoxue Formula low-dose (10.47 g/kg), medium-dose (20.93 g/kg) and high-dose (41.87 g/kg) groups. Each group was given corresponding drugs by gavage for 2 weeks. The embryo loss rate of CBA/J mice after different concentrations of drug intervention was observed; the expressions of VEGFA and VEGFR2 proteins in decidua were detected by immunohistochemistry; the expressions of VEGFA, VEGFR2, PI3K, Akt, p-Akt proteins in decidua were detected by Western blot.,Results,2,①Compared with the model group, the embryo loss rates of the progesterone group and the low-dose, medium-dose and high-dose groups of Bushen Huoxue Formula were significantly decreased (,P,<,0.05). ②The results of immunohistochemistry showed that: compared with the model group, the positive expression of VEGFA protein was increased in the progesterone group, and the medium-dose and high-dose groups of Bushen Huoxue Formula; the positive expression of VEGFR2 protein was increased in the progesterone group and the low-dose, medium-dose and high-dose groups of Bushen Huoxue Formula (,P,<,0.05); compared with the low-dose group of Bushen Huoxue Formula, the positive expression of VEGFA protein in the medium-dose and high-dose groups of Bushen Huoxue Formula was increased (,P,<,0.05). ③Western blot results showed that: compared with the model group, the expressions of VEGFA, VEGFR2, PI3K, p-Akt proteins in the progesterone group, and the low-dose, medium-dose and high-dose groups of Bushen Huoxue Formula were significantly increased (,P,<,0.05); compared with low-dose and medium-dose groups of Bushen Huoxue Formula, the protein expressions of VEGFA, VEGFR2, PI3K and p-Akt in the high-dose group of Bushen Huoxue Formula were significantly increased (,P,<,0.05).,Conclusion,2,Bushen Huoxue Formula can up-regulate the expression of VEGFA and VEGFR2 in decidua of recurrent abortion model mice, and the mechanism may be related to the activation of PI3K/Akt signaling pathway.
关键词
补肾活血方复发性流产小鼠蜕膜组织VEGFPI3K/Akt
Keywords
Bushen Huoxue Formularecurrent abortionmicedecidual tissueVEGFPI3K/Akt
references
谢幸，苟文丽. 妇产科学[M].8版. 北京：人民卫生出版社，2013: 49.
Practice Committee Of American Society For Reproductive Medicine. Multiplegestation associated with infertility therapy: an American Society for Reproductive Medicine Practice Committee opinion[J].Fertil Steril,2012,97(4): 825-834.
BRANCH D W, GIBSON M, SILVER R M. Clinical practice. Recurrent miscarriage[J].N Engl J Med,2010,363(18): 1740-1747.
王婷，孙美娟，何桂林，等. 中西医结合治疗复发性流产的研究进展[J].江西中医药,2017,48(4): 74-77.
王媛中，李元琪，李伟莉. 母胎界面血管生成调控因子与复发性流产的研究[J].长春中医药大学学报,2017,33(6): 979-983.
石玉姣，谢京红. 不明原因复发性流产的中西医发病机制及治疗研究进展[J].北京中医药,2020,39(7): 771-776.
申萌萌，刘雁峰，柳井杜莎，等. PI3K/Akt/eNOS信号通路与胚胎植入和妊娠维持[J].中国生育健康杂志,2017,28(5): 489-492.
LI Z, ZHOU G, JIANG L, et al. Effect of STOX1 on recurrent spontaneous abortion by regulating trophoblast cell proliferation and migration via the PI3K/Akt signaling pathway[J].J Cell Biochem,2018,120(5): 8291-8299.
周旋，冯晓玲. 基于文献研究的复发性流产病因病机及证治规律[J].长春中医药大学学报,2015,31(1): 156-158.
许春月，郭洁，宋殿荣，等. 寿胎丸对复发性流产小鼠蜕膜组织中螺旋动脉改变及怀孕结局的影响[J].国际妇产科学杂志,2017,44(4): 443-447.
李佶，蔡诗莹，戴煜婷，等. 补肾活血法治疗复发性流产的临床观察[J].浙江中医药大学学报,2017,41(8): 677-681.
CLARK D A, MCDERMOTT M R, SCZEWZUK M R. Impairment of host-versusgraftrezction in pregnant mice.Ⅱ.Selective suppression of cytotoxic T-cell generation correlates with soluble suppressor activity and successful allogeneic pregnancy[J].Cell Immunol,1980,52(1): 106-118.
陈奇. 中药药理研究方法学[M].北京：人民卫生出版社，2000: 145.
赵爱民，林其德，鲍世民，等. 自然流产小鼠模型的胚胎丢失率[J].上海实验动物科学,1999,19(4): 26-27.
LI L, DOU L X, LEUNG P C, et al. Chinese herbal medicines for unexplained recurrent miscarriage[J].Cochrane Database Syst Rev,2016,14(1): CD010568.
CLARK D A, CHAOUAT G, ARCK P C, et al. Cytokine-dependent abortion in CBA×DBA/2 mice is mediated by the procoagulant fgl2 prothrombinase[J].J Immunol,1998,160(2): 545-549.
谭展望，雷磊，罗蕾，等. 寿胎丸对复发性流产小鼠蜕膜蛋白质组的影响[J].中国中药杂志,2013,38(4): 591-596.
郝乐乐，李伟莉，吴花，等. 补肾安胎冲剂调控VHL/HIF-1α信号通路改善复发性流产小鼠母胎界面血管生成的实验研究[J].安徽中医药大学学报,2020,39(1): 65-69.
党慧敏，刘艳巧，安鹏，等. 补肾活血方联合地屈孕酮对复发性自然流产患者CD4+ CD25+调节性T细胞及IL-10、TGF-β1表达的影响[J].中华中医药学刊,2015,33(11): 2716-2720.
宋艳丽，孙自学，门波，等. 滋肾健脾化瘀方联合主动免疫治疗对复发性流产肾虚血瘀证患者的临床疗效[J].中成药,2018,40(11): 2394-2399.
何培芝，曾薇薇，沈明洁，等. 活血化瘀法治疗易栓症所致复发性流产研究进展[J].上海中医药杂志,2017,51(8): 109-112.
黄俐华，陈芊.佛手散对先兆流产模型大鼠血流变的影响及流产血瘀病机的探究[J].中国社区医师(医学专业),2012,13(34): 7-8.
高静，李佶. 李佶辨治复发性流产验案1则[J].上海中医药杂志,2012,46(6): 24-25.
KOCH S, CLAESSON-WELSH L. Signal transduction by vascular endothelial growth factor receptors[J].Cold Spring Harb Perspect Med,2012,2(7): a006502.
AMIRCHAGHMAGHI E, REZAEI A, MOINI A, et al. Gene expression analysis of VEGF and its receptors and assessment of its serum level in unexplained recurrent spontaneous abortion[J].Cell J,2015,16(4): 538-545.
TAMMELA T, ENHOLM B, ALITALO K, et al. The biology of vascular endothelial growth factors[J].Cardiovasc Res,2005,65(3): 550-563.
郑素军，林汝仙，王升启.血管内皮生长因子受体-2及其信号转导作用的研究进展[J].国外医学(药学分册),2004,31(6): 337-341.
CÉBE-SUAREZ S, ZEHNDER-FJÄLLMAN A, BALLMER-HOFER K. The role of VEGF receptors in angiogenesis；complex partnerships[J].Cell Mol Life Sci,2006,63(5): 601-615.
向本旭，刘婷婷，孙芳玲，等. VEGF相关信号通路在血管新生中的研究进展[J].中国比较医学杂志,2015,25(12): 81-86.
ZHU R, HUANG Y H, TAO Y, et al. Hyaluronan up-regulates growth and invasion of trophoblasts in an autocrine manner via PI3K/Akt and MAPK/ERK1/2 pathways in early human pregnancy[J].Placenta,2013,34(9): 784-791.
FURMENTO V A, MARINO J, BLANK V C, et al. The granulocyte colony-stimulating factor （G-CSF）upregulates metalloproteinase-2 and VEGF through PI3K/Akt and Erk1/2 activation in human trophoblast Swan 71 cells[J].Placenta,2014,35(11): 937-946.
曹晓梅，李伟莉. 补肾安胎冲剂对复发性流产小鼠蜕膜组织VEGF 及VEGFR2 蛋白表达的影响[J].上海中医药大学学报,2016,30(1): 65-68.
张杨，王玲，李娜，等. 补肾活血方对不明原因复发性流产小鼠蜕膜细胞TNFR1、PI3K/Bcl-xl的影响[J].中华中医药杂志,2017,32(2): 768-771.
韩岚，梁杰，张艳艳，等. 桃红四物汤对产后血瘀大鼠血清NO、子宫组织VEGF的表达及对PI3K/Akt信号通路的影响[J].中华中医药杂志,2016,31(5): 1625-1629.
0
浏览量
695
下载量
0
CSCD
9
CNKI被引量
- 网络PDF下载
- Meta-XML下载
- BibTeX下载
- Endnote下载
- RefMan 下载
- NoteExpress下载
- NoteFirst下载
关联资源
相关文章
相关作者
相关机构
- 技术支持由北京北大方正电子有限公司提供 沪ICP备13044091号
沪公网安备 31011502015228号 - 本系统建议在Chrome、 IE9+ 以上版本浏览器阅读本站内容，360浏览器请切换至极速模式
- Cookies帮助我们提供服务并提供个性化体验。使用本网站，即表示您同意我们使用Cookies
- 总访问量：70551 今日访问量：32