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胶艾汤对模拟特发性流产的线粒体调控作用机制

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目的:探究胶艾汤对模拟特发性流产的线粒体调控作用机制.方法:细胞实验设置对照组、胶艾汤组、miR-29α-3p模拟物组、胶艾汤+miR-29α-3p模拟物组,对人绒毛膜滋养层细胞HTR-8/SVneo进行培养和处理,检测miR-29α-3p表达、线粒体凋亡、细胞色素C释放、凋亡相关蛋白表达、细胞迁移和侵袭能力.动物实验选用怀孕的C57BL/6J小鼠建立流产模型,分组进行胶艾汤灌胃治疗和miR-29α-3p模拟物腹腔注射治疗,观察流产情况、胎盘组织学变化、miR-29α-3p表达、线粒体凋亡相关指标.结果:细胞实验中,与对照组相比,胶艾汤组里miR-29α-3p的表达水平于48 h明显提升(P<0.001),miR-29α-3p模拟物组的表达水平也显著高于对照组,而胶艾汤+miR-29α-3p模拟物组的表达水平最高.胶艾汤和miR-29α-3p模拟物能够降低线粒体膜电位变化,减少细胞色素C的释放,调节凋亡相关蛋白(Bax表达降低,Bcl-2表达升高,Caspase-3活性降低)的表达,使其向抗凋亡方向转变,从而抑制线粒体凋亡,联合使用时效果更优.胶艾汤和miR-29α-3p模拟物还能够促进细胞的迁移和侵袭能力,联合使用时效果更为显著.动物实验中,流产模型组的流产率较高,为(31.17±0.67)%;胶艾汤治疗组的流产率降低至(13.30±0.36)%;胶艾汤+miR-29α-3p模拟物组的流产率进一步降低至(5.77±0.36)%(P<0.001).胶艾汤治疗组胎盘组织的形态和结构得到改善,滋养层细胞的损伤减轻;胶艾汤+miR-29α-3p模拟物组胎盘组织的损伤程度更轻,滋养层细胞形态基本正常.胶艾汤治疗组与胶艾汤+miR-29α-3p模拟物组在胎盘组织中miR-29α-3p的表达水平提升,而且胶艾汤+miR-29α-3p模拟物组的表达水平更高.胶艾汤治疗组和胶艾汤+miR-29α-3p模拟物组胎盘组织中Bax表达降低(P<0.01),Bcl-2表达升高(P<0.001),Caspase-3活性降低(P<0.01).结论:胶艾汤能够上调miR-29α-3p的表达,调控线粒体凋亡,干预滋养层细胞侵袭迁移,降低流产发生风险,miR-29α-3p在其中发挥重要作用.
The mechanism of mitochondrial regulation by Jiao Ai decoction in a model of idiopathic miscarriage
Objective:To explore the mechanism of mitochondrial regulation by Jiao Ai decoction in a model of idiopathic miscarriage.Methods:Cell experiments and animal experiments were conducted.In the cell experiment,the control group,the Jiao Ai decoction group,the miR-29α-3p mimic group,and the Jiao Ai decoction+miR-29α-3p mimic group were set up.Human chorionic trophoblast cells HTR-8/SVneo were cultured and treated,and the ex-pression of miR-29α-3p,mitochondrial apoptosis,cytochrome C release,apoptosis-related protein expression,cell mi-gration and invasion ability were detected.In the animal experiment,pregnant C57BL/6J mice were selected to estab-lish a miscarriage model,and the groups were treated with Jiao Ai decoction by gavage and miR-29α-3p mimic by in-traperitoneal injection.The miscarriage situation,placental histology changes,miR-29α-3p expression,mitochondrial apoptosis-related indicators,and oxidative stress indicators were observed.Results:In the cell experiment,compared with the control group,the expression level of miR-29α-3p in the Jiao Ai decoction group was significantly increased at 48 hours(P<0.001),the expression level in the miR-29α-3p mimic group was also significantly higher than that in the control group,and the expression level in the Jiao Ai decoction+miR-29α-3p mimic group was the highest.Jiao Ai decoction and miR-29α-3p mimic could reduce the change of mitochondrial membrane potential,reduce the release of cytochrome C,regulate the expression of apoptosis-related proteins(Bax expression decreased,Bcl-2 expression in-creased,Caspase-3 activity decreased),and make them shift to the anti-apoptotic direction,thereby inhibiting mito-chondrial apoptosis,and the combined use had a better effect.Jiao Ai decoction and miR-29α-3p mimic could also pro-mote the migration and invasion ability of cells,and the combined use had a more significant effect.In the animal ex-periment,the miscarriage rate in the miscarriage model group was higher,at(31.17±0.67)%.The miscarriage rate in the Jiao Ai decoction treatment group was reduced to(13.30±0.36)%.The miscarriage rate in the Jiao Ai decoc-tion+miR-29α-3p mimic group was further reduced to(5.77±0.36)%(P<0.001).The morphology and structure of placental tissue in the Jiao Ai decoction treatment group were improved,and the damage of trophoblast cells was reduced.The degree of damage to placental tissue in the Jiao Ai decoction+miR-29α-3p mimic group was lighter,and the morphology of trophoblast cells was basically normal.The expression level of miR-29α-3p in placental tissue was increased in the Jiao Ai decoction treatment group and the Jiao Ai decoction+miR-29α-3p mimic group,and the ex-pression level in the Jiao Ai decoction+miR-29α-3p mimic group was higher.In the placental tissue of the Jiao Ai de-coction treatment group and the Jiao Ai Decoction+miR-29α-3p mimic group,Bax expression was decreased(P<0.01),Bcl-2 expression was increased(P<0.001),and Caspase-3 activity was decreased(P<0.01).In the placental tissue of the Jiao Ai decoction treatment group and the Jiao Ai decoction+miR-29α-3p mimic group,SOD activity was increased,MDA content was decreased,and the improvement effect of the Jiao Ai decoction+miR-29α-3p mimic group was better(P<0.001).Conclusion:J iao Ai decoction can up-regulate the expression of miR-29α-3p,regulate mitochondrial apoptosis,intervene in the invasion and migration of trophoblast cells,and reduce the risk of miscar-riage.miR-29α-3p plays an important role in it.

Spontaneous abortionJiao Ai decoctionmiR-29α-3pMitochondrialApoptosisTrophoblast cell

陈西、罗岚、宁东红、谢春红、彭艳丽、梁煦

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湖南省妇幼保健院中医妇科,湖南长沙 410000

自然流产 胶艾汤 miR-29α-3p 线粒体 凋亡 滋养层细胞

2025

陕西中医
陕西省中医药学会

陕西中医

影响因子:1.101
ISSN:1000-7369
年,卷(期):2025.46(1)