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吴茱萸碱对高糖诱导的滋养层细胞增殖、迁移、侵袭的影响及机制
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| 篇名： | 吴茱萸碱对高糖诱导的滋养层细胞增殖、迁移、侵袭的影响及机制 |
| TITLE： | Impact of evodiamine on the proliferation，migration and invasion of trophoblastic cells induced by high glucose and its mechanism |
| 摘要： | 目的 基于晚期糖基化终末产物（AGE）/晚期糖基化终末产物受体（RAGE）信号通路探讨吴茱萸碱对高糖诱导的滋养层细胞增殖、迁移、侵袭能力的影响及潜在机制。方法将人滋养层细胞HTR-8/SVneo分为对照组、高糖组、吴茱萸碱低浓度组（2μmol/L）、吴茱萸碱高浓度组（4μmol/L）、pc-NC组（转染pc-NC质粒+4μmol/L吴茱萸碱）、pc-RAGE组（转染pc-RAGE质粒+4μmol/L吴茱萸碱）。除对照组外的其余各组细胞均在高糖（25mmol/L葡萄糖）环境下培养，除对照组、高糖组外的其余各组细胞均转染相应质粒和（或）接受相应药液干预。检测各组细胞的存活率、凋亡率、划痕愈合率、侵袭数，以及AGE、RAGE、核因子κBp65（NF-κBp65）、基质金属蛋白酶2（MMP-2）、MMP-9蛋白及mRNA的表达情况。结果与对照组比较，高糖组细胞的存活率、划痕愈合率、侵袭数和MMP-2、MMP-9蛋白及mRNA的表达水平均显著降低（P＜0.05），其凋亡率，AGE、RAGE蛋白及mRNA的表达水平，NF-κBp65mRNA的表达水平和NF-κBp65蛋白的磷酸化水平均显著升高（P＜0.05）；与高糖组比较，吴茱萸碱低、高浓度组细胞上述指标均显著改善，且高浓度组的效果显著优于低浓度组（P＜0.05）；过表达RAGE会减弱吴茱萸碱对高糖诱导的滋养层细胞上述指标（AGEmRNA及蛋白除外）的改善作用（P＜0.05）。结论吴茱萸碱可促进高糖诱导的滋养层细胞增殖、迁移、侵袭，改善其功能损伤，上述作用与抑制AGE/RAGE信号通路有关。 |
| ABSTRACT： | OBJECTIVE To investigate the impact of evodiamine on the proliferation， migration and invasion abilities of trophoblastic cells induced by high glucose and its potential mechanism based on advanced glycation end products （AGE）/receptor for advanced glycation end products （RAGE） signaling pathway. METHODS Human trophoblastic cells HTR-8/SVneo were divided into control group， high glucose group， evodiamine low-dose group （2 μmol/L）， evodiamine high-dose group （4 μmol/L）， pc-NC group （transfected with pc-NC plasmid+4 μmol/L evodiamine）， and pc-RAGE group （transfected with pc-RAGE plasmid+ 4 μmol/L evodiamine）. Cells in all groups except for the control group were cultured in a high sugar （25 mmol/L glucose） environment， and cells in all groups except for the control group and the model group were transfected with the corresponding plasmids and/or received the corresponding drug interventions. The survival rate， apoptotic rate， scratch healing rate， and invasion number， as well as the protein and mRNA expressions of AGE， RAGE， nuclear factor- κB p65 （NF- κB p65）， matrix metalloproteinase-2 （MMP-2）， and MMP-9 were examined in each group. RESULTS Compared with the control group， the cell survival rate， scratch healing rate， invasions number， and the mRNA and protein expressions of MMP-2 and MMP-9 in the high glucose group significantly decreased （P＜0.05）， while the apoptotic rate， the mRNA and protein expressions of AGE and RAGE， the mRNA expression of NF-κB p65， and the phosphorylation level of NF-κB p65 protein significantly increased （P＜0.05）； compared with the high glucose group， the above indexes of cells in evodiamine low-dose and high-dose groups were significantly improved， and the effect of the high-dose group was significantly better than that of the low-dose group （P＜0.05）； overexpression of RAGE attenuated the ameliorative effect of evodiamine onthe above indexes in high glucose-induced trophoblast cells （except for AGE mRNA and protein） （P＜0.05）. CONCLUSIONS Evodiamine can promote the proliferation， migration and invasion of high glucose-induced trophoblast cells and ameliorate their functional impairment， and the above effects are associated with the inhibition of the AGE/RAGE signaling pathway. |
| 期刊： | 2024年第35卷第12期 |
| 作者： | 王丽娟；刘元涛；田鹏飞 |
| AUTHORS： | WANG Lijuan，LIU Yuantao，TIAN Pengfei |
| 关键字： | 吴茱萸碱；高糖；滋养层细胞；增殖；迁移；侵袭；AGE/RAGE信号通路 |
| KEYWORDS： | evodiamine； high glucose； trophoblast cells； proliferation； migration；invasion； AGE/RAGE signaling pathway |
| 阅读数： | 6 次 |
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