摘要
探讨孕康口服液对细菌脂多糖(LPS)诱导流产小鼠的保胎及免疫耐受调节作用。ICR正常孕鼠60只,随机分为正常组,模型组,孕康口服液高、中、低3个剂量组,黄体酮组。实验于妊娠第7天尾静脉注射LPS(0.1μg/只),建立小鼠流产模型。从妊娠第0天开始,分别给予蒸馏水,孕康口服液(36,18,9 m L·kg^(-1)·d^(-1)),黄体酮(0.038 g·kg^(-1)·d^(-1))。于妊娠第9天处死小鼠,观察各组小鼠胚胎丢失情况;并采用ELISA法检测母胎界面Th1型细胞因子TNF-α,IFN-γ和Th2型细胞因子IL-4,IL-10水平;HE染色观察蜕膜组织的病理变化;免疫组化法考察子宫组织中CD14,F4/80的表达变化;Western blot法考察子宫蜕膜TLR4,MyD88,NF-κB蛋白表达情况。孕康各剂量组均能显著降低小鼠的胚胎吸收率;高剂量组能显著升高模型小鼠子宫组织中IL-10,IL-4水平,中、高剂量组能降低TNF-α,IFN-γ水平,减少小鼠子宫脱膜组织中TLR4,MyD88,NF-κB蛋白的表达;各给药组均能减少子宫组织F4/80^+,CD14^+巨噬细胞数量和阳性面积。孕康口服液对于LPS诱导致流产小鼠具有良好的保胎作用,其机制可能与抑制TLR4/MyD88/NF-κB信号通路,减少巨噬细胞浸润,调节Th1/Th2型免疫因子平衡,从而改善小鼠子宫内膜容受性,促使蜕膜发育,促进胚泡着床有关。
To investigate the effect of Yunkang Oral Liquid on preventing lipopolysaccharide(LPS)-induced abortion and regulating immune tolerance in mice,sixty normal ICR mice were randomly divided into normal group,model group,Yunkang Oral Liquid high,middle and low dose groups and progesterone group.Abortion model was established by tail vain injection of LPS(0.1μg/mouse)on the 7th day of pregnancy.Since the first day of pregnancy,the same volume of distilled water,Yunkang Oral Liquid at the dose of 36,18 and 9 m L·kg^-1·d^-1,and progesterone at the dose of 0.038 g·kg^-1·d^-1were given in corresponding groups.The mice were sacrificed at the 9th day of pregnancy,and the embryo loss of each group was calculated.The levels of Th1 type cytokines(TNF-α,IFN-γ)and Th2 type cytokines(IL-4,IL-10)in uterus homogenate were detected by ELISA.HE staining was performed to examine the histopathological changes in the decidua.The expression levels of CD14,F4/80 in macrophages of uterus were detected by immunohistochemistry.Western blot was used to investigate the protein expression of TLR4,MyD88 and NF-κB in uterine decidua.In our study,all Yunkang Oral Liquid groups could significantly reduce the embryo absorption rate of mice,while high dose group can significantly increase the levels of IL-10 and IL-4;both medium and high dose groups can significantly decrease TNF-α,and IFN-γlevelsin the uterus of model mice,reduce the protein expression of NF-κB,MyD88 and TLR4 in uterine decidua tissue.Various treatment groups could reduce the counts of F4/80,CD14 macrophages and decrease expression area in uterine tissue.Our results showed that Yunkang Oral Liquid could prevent LPS-induced abortion,and the mechanism may be associated with inhibiting the TLR4/MyD88/NF-κB signaling pathway and regulating the balance of Th1/Th2 immune factors,which could improve the endometrial receptivity of mice,and promote the development of decidua and implantation of embryo.
作者
施秋秋
颜美秋
余欢欢
陈青青
陈素红
吕圭源
SHI Qiu-qiu;YAN Mei-qiu;YU Huan-huan;CHEN Qing-qing;CHEN Su-hong;LYU Gui-yuan(Zhejiang Chinese Medical University,Hangzhou 310053,China;Zhejiang University of Technology,Hangzhou 310014,China)
出处
《中国中药杂志》
CAS
CSCD
北大核心
2019年第6期1227-1232,共6页
China Journal of Chinese Materia Medica
基金
浙江省重点实验室项目(2012E10002)
浙江省"万人计划"科技创新领军人才项目
关键词
孕康口服液
先兆流产
脂多糖(LPS)
母胎免疫耐受
NF-κB信号通路
Yunkang Oral Liquid
threatened abortion
lipopolysaccharide(LPS)
maternal-fetal immune tolerance
NF-κB signaling pathway
