文献类型：期刊文献

中文题名：非奈利酮通过磷脂酰肌醇3-激酶/蛋白激酶B/核因子κB信号通路抑制高糖诱导的心肌成纤维细胞纤维化机制的研究

英文题名：Finerenone inhibits hyperglycemic-induced inflammatory damage mechanisms in myocardial fibroblasts through the phosphoinositide 3-kinase/protein kinase B/nuclear factorκB signaling pathway

作者：马红梅[1,2];何文静[1];武振亚[1];王飞茹[3];王丽娟[1];刘胜男[1];汤惠惠[1];王紫琼[1];杨文[1];王金羊[4]

第一作者：马红梅

机构：[1]甘肃中医药大学第一临床医学院,兰州730000;[2]临夏州人民医院疼痛科;[3]兰州大学第一临床医学院;[4]甘肃省人民医院内分泌科

第一机构：甘肃中医药大学临床医学院

年份：2026

卷号：34

期号：2

起止页码：123

中文期刊名：中国糖尿病杂志

外文期刊名：Chinese Journal of Diabetes

收录：;北大核心:【北大核心2023】；

基金：国家自然科学基金(81760147、81560143、82360163);甘肃省自然科学基金(21JR1RA013、24JRRA589);兰州大学研究生“创新之星”项目(2025CXZX-208)。

语种：中文

中文关键词：非奈利酮;心肌成纤维细胞;炎症;纤维化

外文关键词：Finerenone;Myocardial fibroblasts;Inflammation;Fibrosis

摘要：目的探讨非奈利酮通过磷脂酰肌醇3-激酶/蛋白激酶B/核因子κB(PI3K/Akt/NF-κB)信号通路对高糖(HG)诱导的心肌成纤维细胞(CFs)抗炎、抗纤维化的作用及其可能机制。方法小鼠CFs分为对照(Con)组、HG组、HG+非奈利酮干预(HG+Fin)组。CCK8法检测非奈利酮最佳浓度,qRT-PCR检测PI3K、Akt、NF-κB、IL-β、IL-6、TNF-α、胶原蛋白(COL)Ⅰ、COLⅢmRNA表达,免疫荧光观察盐皮质激素受体(MR)、PI3K、Akt、NF-κB荧光强度,Western blot检测PI3K、p-PI3K、Akt、p-Akt、NF-κB、p-NF-κB蛋白表达。结果与Con组比较,HG组MR、PI3K、Akt、NF-κB平均荧光强度、mRNA表达升高(P<0.05),IL-1β、IL-6、TNF-α、COLⅠ和COLⅢmRNA表达升高(P<0.05),PI3K、p-PI3K、Akt、p-Akt、NF-κB、p-NF-κB蛋白表达升高(P<0.05)。与HG组比较,HG+Fin组MR、PI3K、Akt、NF-κB平均荧光强度、mRNA表达降低(P<0.05),IL-1β、IL-6、TNF-α、COLⅠ和COLⅢmRNA表达降低(P<0.05),PI3K、p-PI3K、Akt、p-Akt、NF-κB、p-NF-κB蛋白表达降低(P<0.05)。结论非奈利酮可抑制HG诱导的CFs炎症标志物及纤维化标志物合成,发挥抗炎抗纤维化作用,其机制可能与下调PI3K/Akt/NF-κB信号通路相关。
Objective To explore the anti-inflammatory and anti-fibrotic effects of Finerenone on high glucose(HG)-induced cardiac fibroblasts(CFs)and its possible mechanism through the phosphatidylinositol 3-kinase/protein kinase B/nuclear factorκB(PI3K/Akt/NF-κB)signaling pathway.Methods Mouse CFs were divided into control(Con)group,HG group,and HG+Finerenone intervention(HG+Fin)group.The optimal concentration of Finerenone was detected by CCK8 assay.qRT-PCR was used to evaluate the mRNA expression of PI3K,Akt,NF-κB,interleukin(IL)-1β,IL-6,tumor necrosis factor(TNF)-α,collagen fiber(COL)I,and COLⅢ.Immunofluorescence was used to detect the fluorescence intensity of mineralocorticoid receptor(MR),PI3K,Akt,and NF-κB.Western blot was used to assessthe protein expression of PI3K,p-PI3K,Akt,p-Akt,NF-κB,and p-NF-κB.Results Compared with the Con group,the HG group exhibited increased mean fluorescence intensity and mRNA expression of MR,PI3K,Akt,and NF-κB(P<0.05),as well as elevated increased mRNA expression of IL-1β,IL-6,TNF-α,COL I,and COLⅢ(P<0.05).Additionally,protein expression of PI3K,p-PI3K,Akt,p-Akt,NF-κB,and p-NF-κB was also elevated increased(P<0.05).Compared with the HG group,the HG+Fin group showed decreased mean fluorescence intensity and mRNA expression of MR,PI3K,Akt,and NF-κB(P<0.05),along with reduced mRNA expression of IL-1β,IL-6,TNF-α,COL I,and COLⅢ(P<0.05).However,protein expression of PI3K,p-PI3K,Akt,p-Akt,NF-κB,and p-NF-κB were elevated decreased(P<0.05).Conclusions Finerenone exerts anti-inflammatory and anti-fibrotic effects in HG-induced CFs by suppressing the synthesis of relevant markers,likely through downregulating the PI3K/Akt/NF-κB signaling pathway.