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Effect of Pangshi Antai Zhixue Decoction on Th1/Th2 Balance in Decidua and Membrane of Spontaneous Abortion Rats with Heat Syndrome by Regulating p38 MAPK Signal Pathway
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 28, Issue 18, Pages: 62-69(2022)
- 作者机构：
1.河南中医药大学，郑州 450046
2.河南省中医院，郑州 450000
3.河南中医药大学 第三附属医院，郑州 450008
- 作者简介：
- 基金信息：
DOI：10.13422/j.cnki.syfjx.20221101
CLC： R2-0;R22;R285.5;R289;R33Published：20 September 2022，
Published Online：25 March 2022，
Received：05 January 2022，
- 稿件说明：
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马丽亚,蔡园园,张雪琳等.庞氏安胎止血汤通过调控p38 MAPK信号通路干预热证自然流产大鼠蜕膜组织Th1/Th2平衡的机制[J].中国实验方剂学杂志,2022,28(18):62-69.
MA Liya,CAI Yuanyuan,ZHANG Xuelin,et al.Effect of Pangshi Antai Zhixue Decoction on Th1/Th2 Balance in Decidua and Membrane of Spontaneous Abortion Rats with Heat Syndrome by Regulating p38 MAPK Signal Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(18):62-69.
马丽亚,蔡园园,张雪琳等.庞氏安胎止血汤通过调控p38 MAPK信号通路干预热证自然流产大鼠蜕膜组织Th1/Th2平衡的机制[J].中国实验方剂学杂志,2022,28(18):62-69. DOI： 10.13422/j.cnki.syfjx.20221101.
MA Liya,CAI Yuanyuan,ZHANG Xuelin,et al.Effect of Pangshi Antai Zhixue Decoction on Th1/Th2 Balance in Decidua and Membrane of Spontaneous Abortion Rats with Heat Syndrome by Regulating p38 MAPK Signal Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(18):62-69. DOI： 10.13422/j.cnki.syfjx.20221101.
摘要
目的
2
基于p38丝裂原活化蛋白激酶（p38 MAPK）信号通路探讨庞氏安胎止血汤的保胎作用及对蜕膜组织辅助性T细胞（Th）1/Th2平衡的影响机制研究。
方法
2
采用灌胃附子、干姜、肉桂水煎剂方式制备热证自然流产大鼠模型。将模型大鼠随机分为模型组、阿司匹林组（5.25 mg·kg
-1
）、地屈孕酮组（3.02 mg·kg
-1
）和庞氏安胎止血汤低、中、高剂量组（11、22、44 g·kg
-1
），每组10只，另取10只作为正常组。各组大鼠依据组别给予相应药物干预，1次/d，连续干预12 d，末次给药24 h后，腹主动脉取血，酶联免疫吸附测定法（ELISA）检测
β
-绒毛膜促性腺激素（
β
-HCG）、孕激素（P）、雌二醇（E
2
）、
γ
干扰素（IFN-
γ
）、白细胞介素-4（IL-4）水平；取大鼠子宫及蜕膜组织，测定流产数和流产率；采用蛋白免疫印迹法（Western blot）检测蜕膜组织中GATA3、T-bet、p38 MAPK及其磷酸化水平。
结果
2
与正常组比较，模型组大鼠活胎数和血清
β
-HCG、P、E
2
、IL-4及蜕膜组织GATA3蛋白水平显著降低（
P
<
0.01），流产数、流产率、血清IFN-
γ
及脱模组织p-p38 MAPK、T-bet蛋白水平显著升高（
P
<
0.01）；与模型组比较，庞氏安胎止血汤中剂量组大鼠活胎数和血清
β
-HCG、P、E
2
、IL-4及蜕膜组织GATA3蛋白水平显著升高（
P
<
0.01），流产数、流产率、血清IFN-
γ
及脱模组织p-p38 MAPK、T-bet蛋白水平显著降低（
P
<
0.01）；与阿司匹林组比较，地屈孕酮组和庞氏安胎止血汤中、高剂量组大鼠血清P、E
2
、IL-4水平显著上高（
P
<
0.01），庞氏安胎止血汤中剂量组大鼠活胎数显著升高（
P
<
0.01），地屈孕酮组大鼠血清
β
-HCG、IFN-
γ
水平显著降低（
P
<
0.01），庞氏安胎止血汤中剂量组大鼠流产数、流产率、血清IFN-
γ
及蜕膜组织T-bet、GATA3水平明显降低（
P
<
0.05）；与庞氏安胎止血汤中剂量组比较，庞氏安胎止血汤低、高剂量组和地屈孕酮组大鼠流产数及流产率明显升高（
P
<
0.05），庞氏安胎止血汤高剂量组和地屈孕酮大鼠活胎数显著降低（
P
<
0.01），庞氏安胎止血汤低剂量组大鼠血清IFN-
γ
、蜕膜组织p-p38 MAPK、T-bet蛋白水平明显升高（
P
<
0.05），庞氏安胎止血汤高剂量组大鼠蜕膜组织p-p38 MAPK、T-bet蛋白水平明显升高（
P
<
0.05），庞氏安胎止血汤低剂量组、地屈孕酮组和阿司匹林组大鼠血清
β
-HCG、P、E
2
水平显著降低（
P
<
0.01），庞氏安胎止血汤低、高剂量组和地屈孕酮组大鼠血清IL-4和蜕膜组织GATA3蛋白水平显著降低（
P
<
0.01）。
结论
2
庞氏安胎止血汤通过调控p38 MAPK信号通路，调节Th1/Th2平衡，从而实现保胎作用。
Abstract
Objective
2
To explore the anti-abortional effect of Pangshi Antai Zhixue decoction and its mechanism in helper T lymphocyte 1 （Th1）/Th2 balance in the decidual tissues of spontaneous abortion rats with heat syndrome， based on the p38 mitogen-activated protein kinase （p38 MAPK） signaling pathway.
Method
2
Aconiti Lateralis Radix Praeparata， Zingiberis Rhizoma， and Cinnamomi Cortex decoction was used to replicate the rat model of spontaneous abortion with heat syndrome. The spontaneous abortion rats with heat syndrome were randomly divided into model group， aspirin group （5.25 mg·kg
-1
）， dydrogesterone group （3.02 mg·kg
-1
）， Pangshi Antai Zhixue decoction high-dose （44 g·kg
-1
）， medium-dose （22 g·kg
-1
）， and low-dose （11 g·kg
-1
） groups， with ten rats in each group. Ten normal rats were divided into a normal group. Rats in each group were given corresponding drugs， Once a day for 12 d. After 24 h of the last administration， blood was collected from the abdominal aorta. The enzyme-linked immunosorbent assay （ELISA） was used to determine the levels of
β-
human chorionic gonadotropin （
β
-HCG）， progesterone （P）， estradiol （E
2
），
γ
interferon
（IFN-
γ
）， and interleukin-4 （IL-4） in rat serum. The uterus and meconium tissues of rats were collected to determine the number and rate of miscarriages. Western blot was used to detect GATA3， T-bet， p38 MAPK， and its phosphorylation in the decidual tissue.
Result
2
As compared with the normal group， the number of live births， the
β
-HCG， P， E
2
， and IL-4 in the serum， and the GATA3 protein expression in the decidual tissue in the model group were reduced （
P
<
0.01）， whereas the number and rate of miscarriages， IFN-
γ
in the serum， and the expression of p-p38 MAPK and T-bet protein levels in the demolded tissues increased （
P
<
0.01）. As compared with the model group， the number of live births， the
β
-HCG， P， E
2
， and IL-4 in the serum， and the GATA3 protein expression in the decidual tissue in the Pangshi Antai Zhixue decoction medium-dose group increased （
P
<
0.01）， whereas the number and rate of miscarriages， IFN-
γ
in the serum， and the expression of p-p38 and T-bet protein levels in the demolded tissues reduced （
P
<
0.01）. As compared with the aspirin group， the P， E
2
， and IL-4 in the serum of rats in the dydrogesterone group and the Pangshi Antai Zhixue decoction high-dose and medium-dose groups increased （
P
<
0.01）， the number of live births in the Pangshi Antai Zhixue decoction medium-dose group increased （
P
<
0.01）， and the
β
-HCG and IFN-
γ
in the serum of rats in the dydrogesterone group decreased （
P
<
0.01）. The number and rate of miscarriages， IFN-
γ
in the serum， and T-bet and GATA3 levels in the decidual tissues of rats in the Pangshi Antai Zhixue decoction medium-dose group decreased （
P
<
0.05）. Compared with the Pangshi Antai Zhixue decoction medium-dose group， the low-dose group， high-dose group， and dydrogesterone group showed increased number and rate of miscarriages （
P
<
0.05）， and the high-dose group and dydrogesterone group decreased the number of live birth （
P
<
0.01）. The IFN-
γ
in the serum and p-p38 MAPK and T-bet protein in the decidual tissue in the low-dose group， and the p-p38 MAPK and T-bet protein in the decidual tissue in the high-dose group all increased （
P
<
0.05）. The
β
-HCG， P， and E
2
in the serum of rats in the Pangshi Antai Zhixue decoction low-dose group， dydrogesterone group， and aspirin group decreased （
P
<
0.01）， and the IL-4 in the serum and GATA3 in the decidual tissue of rats in the Pangshi Antai Zhixue decoction low-dose and high-dose group and the dydrogesterone group decreased （
P
<
0.01）.
Conclusion
2
Pangshi Antai Zhixue decoction realizes the effect of fetal protection by regulating the activation of p38 MAPK signal pathways and Th1/Th2 balance.
关键词
庞氏安胎止血汤p38 丝裂原活化蛋白激酶（p38 MAPK）信号通路辅助性T细胞（Th）1/Th2平衡热证自然流产
Keywords
Pangshi Antai Zhixue decoctionp38 mitogen-activated protein kinase （p38 MAPK） pathwayhelper T lymphocyte 1 （Th1）/Th2 balancespontaneous abortion with heat syndrome
references
LANJEWAR S，JAYAKUMAR R，AXIOTIS C A.Loss of placental P-glycoprotein may be a common pathophysiologic pathway for first trimester spontaneous miscarriages［J］.Pediatr Dev Pathol，2019，22（5）：456-460.
WANG Y，LIU H Z，LIU Y，et al.Disordered p53-MALAT1 pathway is associated with recurrent miscarriage［J］.Kaohsiung J Med Sci，2019，35（2）：87-94.
HUANG Z，DU G，HUANG X，et al.The enhancer RNA lnc-SLC4A1-1 epigenetically regulates unexplained recurrent pregnancy loss （URPL） by activating CXCL8 and NF-κB pathway［J］.Ebiomedicine，2018，38：162-170.
WANG S，CHEN C，LI M，et al.Blockade of CTLA-4 and Tim-3 pathways induces fetal loss with altered cytokine profiles by decidual CD4+T cells［J］.Cell Death Dis，2019，10（1）：15.
VERMA P，VERMA R，NAIR R R，et al.Altered crosstalk of estradiol and progesterone with Myeloid-derived suppressor cells and Th1/Th2 cytokines in early miscarriage is associated with early breakdown of maternal-fetal tolerance［J］.Am J Reprod Immunol，2019，81（2）：e13081.
WU L，LI J，XU H L，et al.IL-7/IL-7R signaling pathway might play a role in recurrent pregnancy losses by increasing inflammatory Th17 cells and decreasing Treg cells［J］.Am J Reprod Immunol，2016，76（6）：454-464.
TERSIGNI C，D'IPPOLITO S，DI NICUOLO F，et al.Recurrent pregnancy loss is associated to leaky gut： A novel pathogenic model of endometrium inflammation？［J］.J Transl Med，2018，16（1）：102.
JI J，ZHAI H，ZHOU H，et al.The role and mechanism of vitamin d-mediated regulation of Treg/Th17 balance in recurrent pregnancy loss［J］.Am J Reprod Immunol，2019，81（6）：e13112.
CHEN Z，LIU Q，ZHU Z，et al.Toll-like receptor 4 contributes to uterine activation by upregulating pro-inflammatory cytokine and CAP expression via the NF-κB/p38 MAPK signaling pathway during pregnancy［J］.J Cell Physiol，2020，235（1）：513-525.
马丽亚，张颖，庞玉琴，等.庞氏安胎止血汤对热证自然流产大鼠T细胞亚群表达干预的研究［J］.时珍国医国药，2018，29（11）：2632-2635.
马丽亚，张大伟，张颖，等.庞氏安胎汤对先兆流产大鼠血清免疫因子及激素水平的影响［J］.中医杂志，2019，60（2）：159-162.
陈群，刘亚梅，徐志伟，等.实热证、虚热证大鼠血清T3、T4、rT3、TSH含量变化及意义［J］.国医论坛，2000（1）：44-45.
马丽亚，赵君玫，王磊，等.CBA/J小鼠虚热型反复自然流产模型的建立［J］.中医学报，2020，35（2）：358-361.
张大伟，杜玉洁，张颖，等.庞清治诊治热证滑胎经验［J］.中医学报，2017，32（5）：753-757.
张大伟.庞清治治疗热证胎漏、胎动不安的经验［J］.中国中医基础医学杂志，2010，16（9）：839-840.
马丽亚，张大伟，张颖，等.庞氏安胎止血汤治疗先兆流产血热证临床疗效及对T淋巴细胞亚群因子的影响［J］.中华中医药杂志，2021，36（5）：3049-3052.
蔡园园，张大伟教授治疗先兆流产的用药规律分析及经验总结［D］.郑州：河南中医药大学，2019.
鲁文杰，吕圭源，徐俞悦，等.孕康口服液及其不同药效部位对肾虚流产大鼠外周血及Th1/Th2细胞因子的影响［J］.中药药理与临床，2017，33（5）：134-137.
HUANG C，BI J.Expression regulation and function of T-Bet in NK cells［J］.Front Immunol，2021，12：761920.
DAS A，RANGANATHAN V，UMAR D，et al.Effector/memory CD4 T cells making either Th1 or Th2 cytokines commonly co-express T-bet and GATA3［J］.PLoS One，2017，12（10）：e0185932.
FUJIWARA T.GATA transcription factors： Basic principles and related human disorders［J］.Tohoku J Exp Med，2017，242（2）：83-91.
方志红，刘华.T淋巴细胞亚群、NK细胞及Th1/Th2细胞因子与先兆流产发病的关系［J］.江苏医药，2014，40（9）：1070-1072.
HOYLER T，CONNOR C A，KISS E A，et al.T-bet and Gata3 in controlling type 1 and type 2 immunity mediated by innate lymphoid cells［J］.Curr Opin Immunol，2013，25（2）：139-147.
TINDEMANS I，SERAFINI N，DI SANTO J P，et al.GATA3 function in innate and adaptive immunity［J］.Immunity，2014，41（2）：191-206.
SAHOO A，WALI S，NURIEVA R.T helper 2 and T follicular helper cells： Regulation and function of interleukin-4［J］.Cytokine Growth Factor Rev，2016，30：29-37.
HU B，FENG X，WANG L，et al.5-BDBD ameliorates an OVA-induced allergic asthma by the reduction of Th2 cytokines production［J］.Iran J Basic Med Sci，2018，21（4）：364-369.
肖敏，徐洪来，吴栋杰，等.黄芩苷对泛发性脓疱型银屑病患者机体Th1/Th2失衡及T-bet/GAGA-3表达的影响［J］.广西医学，2021，43（16）：1972-1976，1992.
LI W，GENG L，LIU X，et al.Recombinant adiponectin alleviates abortion in mice by regulating Th17/Treg imbalance via p38 MAPK-STAT5 pathway［J］.Biol Reprod，2019，100（4）：1008-1017.
ZHU M，SUN W J，WANG Y L，et al.P38 participates in spermatogenesis and acrosome reaction prior to fertilization in Chinese mitten crab Eriocheir sinensis［J］.Gene，2015，559（2）：103-111.
赵德萍，李大龙，张晏航，等.骨碎补总黄酮调控ER-p38 MAPK信号通路改善东莨菪碱模型小鼠学习记忆功能障碍机制研究［J］.中国中药杂志，2021，46（22）：5922-5929.
张培培，杨欣，梁国强，等.加味白头翁汤通过p38 MAPK-MLCK信号通路影响溃疡性结肠炎模型大鼠肠黏膜紧密连接蛋白［J］.中国中药杂志，2021，46（21）：5719-5726.
ZHANG L M，ZHEN R R，GU C，et al.Chinese medicine Di-Huang-Yi-Zhi protects PC12 cells from H2O2-induced apoptosis by regulating ROS-ASK1-JNK/p38 MAPK signaling［J］.BMC Complement Med Ther，2020，20（1）：54.
江丹，汪何，姚楠，等.基于TGF-β1/p38MAPK通路探讨益气升清方对糖尿病大鼠肾组织的影响［J］.世界中医药，2020，15（16）：2381-2386.
LO M，WANG Y Z，GOUT P W.The x（c）- cystine/glutamate antiporter： A potential target for therapy of cancer and other diseases［J］.J Cell Physiol，2008，215（3）：593-602.
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