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基于JAK2/STAT3、PI3K/AKT双通路研究清热安胎方改善血热型先兆流产大鼠妊娠结局的作用机制
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| 篇名： | 基于JAK2/STAT3、PI3K/AKT双通路研究清热安胎方改善血热型先兆流产大鼠妊娠结局的作用机制 |
| TITLE： | Mechanism of Qingre antai decoction in improving pregnancy outcomes of threatened abortion rats with blood heat syndrome based on JAK2/STAT3 and PI3K/AKT dual signaling pathways |
| 摘要： | 目的 研究清热安胎方改善血热型先兆流产大鼠妊娠结局的作用机制。方法将妊娠成功的大鼠随机分为正常组、模型组、地屈孕酮组（0.002g/kg）和清热安胎方组（44.1g/kg），每组13只。除正常组外，其余各组大鼠自妊娠第1天开始灌胃温阳中药和相应药物，每天1次，连续12d；妊娠第13天一次性灌胃米非司酮（5mg/kg）建立血热型先兆流产模型。妊娠第14天，计算大鼠流产率及子宫系数，观察大鼠妊娠子宫病理学形态，检测大鼠血清中三碘甲状腺原氨酸（T3）、甲状腺素（T4）、促甲状腺激素（TSH）水平，检测大鼠妊娠子宫中血管内皮生长因子（VEGF）、一氧化氮（NO）水平和Janus激酶2（JAK2）/信号转导与转录激活因子3（STAT3）、磷脂酰肌醇3-激酶（PI3K）/蛋白激酶B（AKT）通路相关mRNA及蛋白表达水平。结果与正常组比较，模型组大鼠子宫内膜组织出现损伤、蜕膜细胞数量减少，宫内可见大量瘀血；流产率，血清中T3、T4、TSH水平，子宫中JAK2、STAT3、细胞因子信号转导抑制因子3（SOCS3）mRNA表达水平和磷酸化JAK2、磷酸化STAT3、SOCS3蛋白表达水平均显著升高（P＜0.05）；子宫系数，妊娠子宫中VEGF、NO水平，血管内皮细胞生长因子受体2（VEGFR2）、PI3K、AKT、一氧化氮合酶（eNOS）mRNA表达水平，VEGFR2、PI3K、eNOS蛋白表达水平和AKT蛋白磷酸化水平均显著降低（P＜0.05）。与模型组比较，清热安胎组大鼠子宫内膜组织损伤及充血程度明显改善，上述定量指标水平均显著逆转（P＜0.05）。结论清热安胎方可改善血热型先兆流产大鼠的妊娠结局，其作用机制可能与抑制JAK2/STAT3通路、激活PI3K/AKT通路有关。 |
| ABSTRACT： | OBJECTIVE To explore the mechanism by which Qingre antai decoction improves pregnancy outcomes of threatened abortion rats with blood heat syndrome. METHODS The pregnant rats were randomly divided into normal group， model group， dydrogesterone group （0.002 g/kg）， and Qingre antai decoction group （44.1 g/kg）， with 13 rats in each group. Except for normal group， other groups were given warming-yang Chinese medicine and corresponding drugs intragastrically， once a day， for 12 consecutive days. On the 13th day of pregnancy， a single intragastric administration of mifepristone （5 mg/kg） was performed to establish a model of threatened abortion with blood heat syndrome. On the 14th day of pregnancy， the abortion rate and uterine coefficient were calculated； the pathological morphology of pregnant uterine was observed； the serum levels of 3，5，3′-triiodothyronine （T3）， thyroid hormone （T4）， thyroid stimulating hormone （TSH）， as well as the levels of vascular endothelial growth factor （VEGF） and nitric oxide （NO） in the pregnant uterus were all determined； the expressions of mRNA and protein related to Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） and phosphatidylinositol 3-kinase （PI3K）/protein kinase B （AKT） pathways were detected. RESULTS Compared with normal group， the model group exhibited endometrial tissue damage， a reduced number of decidual cells， and a significant presence of blood stasis within the uterus； abortion rate， the serum levels of T3， T4 and TSH， the mRNA expressions of JAK2， STAT3 and suppressor of cytokine signaling 3 （SOCS3） as well as protein expressions of p-JAK2， p-STAT3 and SOCS3 in the pregnant uterus were increased significantly （ P ＜0.05）； uterine coefficient， the levels of VEGF and NO in pregnant uterus， mRNA expressions of VEGFR2， PI3K， AKT and endothelial nitric oxide synthase（eNOS）， protein expressions of VEGFR2， PI3K and eNOS as well as phosphorylation level of AKT in the pregnant uterus were significantly reduced （ P ＜0.05）. Compared with model group， the endometrial tissue damage and congestion in the Qingre antai decoction group were significantly improved， and the levels of the aforementioned quantitative indicators were significantly reversed （ P ＜0.05）. CONCLUSIONS Qingre antai decoction can improve the pregnancy outcomes in rats with threatened abortion of blood heat syndrome， the mechanism of which may be associated with inhibiting JAK2/STAT3 pathway and activating PI3K/AKT pathway. |
| 期刊： | 2026年第37卷第09期 |
| 作者： | 马丽亚；申艳朵；张家乐；吴刘俊；谢秉恒；吴星霏；刘晨；张明昊；张雪琳；张大伟 |
| AUTHORS： | MA Liya，SHEN Yanduo，ZHANG Jiale， WU Liujun，XIE Bingheng，WU Xingfei，LIU Chen，ZHANG Minghao，ZHANG Xuelin，ZHANG Dawei |
| 关键字： | 清热安胎方；血热；先兆流产；JAK2/STAT3通路；PI3K/AKT通路；妊娠结局 |
| KEYWORDS： | Qingre antai decoction； blood heat syndrome； threatened abortion； JAK2/STAT3 pathway； PI3K/AKT pathway； |
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