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菟丝子黄酮促进蜕膜化改善复发性流产的作用机制研究
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| 篇名： | 菟丝子黄酮促进蜕膜化改善复发性流产的作用机制研究 |
| TITLE： | Study on the mechanism of Cuscuta chinensis flavonoids promoting decidualization and improving recurrent spontaneous abortion |
| 摘要： | 目的 探讨菟丝子黄酮（CCF）促进蜕膜化改善复发性流产（RSA）的作用机制。方法将对数生长期的HTR-8/SVneo细胞随机分为空白组、脂多糖（LPS）组、CCF组、血清和糖皮质激素调节激酶2（SGK2）抑制剂（GSK650394，简称“GSK”）组、CCF+GSK组，分别给予相应药物处理；将敲低SGK2的HTR-8/SVneo细胞随机分为SGK2的小干扰RNA（siSGK2）组、siSGK2+CCF组，并另设空白组、LPS组，分别给予相应药物处理。检测敲低SGK2前后各组细胞的存活率、WNK信号通路及蜕膜化相关蛋白和mRNA表达水平以及敲低后的线粒体膜电位水平。构建RSA小鼠模型，随机分为模型组、CCF低剂量组、CCF高剂量组、GSK组、联合给药组，每组4只；另选4只正常妊娠小鼠作为对照组。记录小鼠胚胎着床数、活胎数和丢失胚胎数，观察小鼠子宫内膜结构及蜕膜化情况，检测WNK信号通路及蜕膜化相关蛋白和mRNA表达水平以及线粒体膜电位水平。结果与空白组比较，LPS组细胞存活率，以及SGK2、WNK1、WNK4、催乳素、胰岛素样生长因子结合蛋白1、氧化应激反应激酶1、Ste20相关脯氨酸/丙氨酸丰富激酶的蛋白及mRNA的表达水平均显著降低（P＜0.05）；与LPS组比较，CCF组细胞存活率和上述蛋白及mRNA的表达水平均显著升高，而GSK组细胞存活率和上述蛋白及mRNA的表达水平均显著降低（P＜0.05）；与CCF组比较，CCF+GSK组细胞存活率和上述蛋白及mRNA表达水平均显著降低（P＜0.05）。敲低SGK2后，与LPS组比较，siSGK2组细胞存活率、红/绿荧光强度比值和上述蛋白及mRNA的表达水平均显著降低（P＜0.05）；与siSGK2组比较，siSGK2+CCF组细胞存活率、红/绿荧光强度比值和上述蛋白及mRNA表达水平均显著增加（P＜0.05）。体内实验结果显示，CCF治疗可显著改善RSA模型小鼠胚胎着床数、活胎数并减少胚胎丢失，子宫内膜组织中上述蛋白及mRNA表达水平均显著升高，并显著提升红/绿荧光强度比值（P＜0.05）；联合给药组可逆转CCF的作用（P＜0.05）。结论CCF可激活SGK2，上调WNK信号通路，促进子宫内膜蜕膜化，进而改善RSA。 |
| ABSTRACT： | OBJECTIVE To explore the mechanism by which Cuscuta chinensis flavonoids （CCF） promote decidualization and improve recurrent spontaneous abortion （RSA）. METHODS HTR-8/SVneo cells in logarithmic growth phase were randomly divided into blank group， lipopolysaccharide （LPS） group， CCF group， SGK2 inhibitor （GSK650394， abbreviated as “GSK”） group and CCF+GSK group. Each group was treated with the corresponding agents accordingly. HTR-8/SVneo cells with SGK2 knockdown were randomly divided into small interfering RNA of SGK2 （siSGK2） group and siSGK2+CCF group； additionally， blank group and LPS group were established； each group was treated with the corresponding agents accordingly. The cell survival rate， expression levels of WNK signaling pathway- and decidualization-related proteins and mRNAs， as well as mitochondrial membrane potential levels， were assessed in each group before and after SGK2 knockdown. RSA mice model was constructed and randomly divided into model group， CCF low-dose group， CCF high-dose group， GSK group， and combined dosing group， with 4 mice in each group. Other 4 normal pregnant female mice were selected as the control group. The number of implanted embryos， viable fetuses， and lost embryos in mice was recorded. The morphological changes of endometrium and decidualization were observed， and WNK signaling pathway- and decidualization-related proteins and mRNAs expressing levels as well as mitochondrial membrane potential levels were all detected. RESULTS Compared with the blank group， the cell survival rate， as well as the protein and mRNA expression levels of SGK2， WNK1， WNK4， prolactin， insulin-like growth factor- binding protein-1， oxidative stress responsive kinase 1， and Ste20-like proline-/alanine-rich kinase were significantly reduced in the LPS group （P＜0.05）； compared with the LPS group， the cell survival rate and the expression levels of the above- mentioned proteins and mRNAs were significantly increased in the CCF group， while the cell survival rate and the expression levels of the above-mentioned proteins and mRNAs were significantly decreased in the GSK group （P＜0.05）； compared with the CCF group， the cell survival rate and the expression levels of the above-mentioned proteins and mRNAs were significantly reduced in the CCF+GSK group （P＜0.05）. After knocking down SGK2， compared with the LPS group， the cell survival rate， red/green fluorescence intensity ratio， and the expression levels of the above-mentioned proteins and mRNAs were significantly reduced in the siSGK2 group （P＜0.05）； compared with the siSGK2 group， the cell survival rate， red/green fluorescence intensity ratio， and the expression levels of the above-mentioned proteins and mRNAs were significantly increased in the siSGK2+CCF group （P＜0.05）. The in vivo experimental results showed that CCF treatment can significantly improve the number of implanted embryos and viable fetuses in RSA model mice and reduce lost embryos， the expression levels of the above-mentioned proteins and mRNAs in endometrial tissue were significantly increased， and the red/green fluorescence intensity ratio was significantly increased （P＜ 0.05）； the combined dosing group could reverse the effect of CCF （P＜0.05）. CONCLUSIONS CCF can activate SGK2， up- regulate the WNK signaling pathway， promote endometrial decidualization， and improve RSA. |
| 期刊： | 2025年第36卷第19期 |
| 作者： | 方芳；崔英；黄嘉膂；陈莉莉；徐佳；万云慧 |
| AUTHORS： | FANG Fang，CUI Ying，HUANG Jialü，CHEN Lili，XU Jia，WAN Yunhui |
| 关键字： | 菟丝子黄酮；复发性流产；WNK信号通路；血清和糖皮质激素调节激酶2；蜕膜化 |
| KEYWORDS： | Cuscuta chinensis flavonoids； recurrent spontaneous abortion； WNK signaling pathway； serum and glucocorticoid |
| 阅读数： | 5 次 |
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