摘要
目的基于Wnt/β-catenin信号途径探讨丹酚酸B(salvianolic acid B,Sal B)对高糖诱导心肌成纤维细胞(car-diac fibroblasts,CFs)增殖及转分化的影响。方法SD大鼠乳鼠CFs,高糖诱导,CCK-8检测不同浓度葡萄糖诱导CFs增殖的浓度及时间效应;加Sal B(12.5、25、50μmol·L^-1)预处理CFs,确定Sal B最佳给药浓度。天狼猩红染色观察胶原纤维沉积;免疫荧光及Western blot检测α-SMA表达,Western blot检测p-GSK 3β、β-catenin表达。结果与正常对照组相比,25 mmol·L^-1高糖刺激CFs24 h明显促进CFs增殖及转分化(P<0.01),增加胶原纤维沉积,α-SMA、β-catenin、p-GSK 3β表达增加;与高糖组比较,经Sal B(25μmol·L^-1)及XAV939(1μmol·L^-1)预处理后,CFs增殖明显抑制(P<0.01),胶原纤维沉积减少,α-SMA、β-catenin、p-GSK 3β表达降低(P<0.01)。结论Sal B可抑制高糖诱导CFs增殖及转分化,其机制可能与抑制Wnt/β-catenin信号通路有关。
Aim To investigate the effects of salvianol-ic acid B(Sal B)onproliferation and transdifferentia-tion of high glucose-induced cardiac fibroblasts(CFs)based on the Wnt/beta-catenin signalling pathway.Methods CFs0f SD rats were induced by high glu-cose.CCK8 was performed to detect the concentration and time effects of the CFsproliferation at different glu-cose concentrations.Sal B(12.5,25,50μmol·L^-1)was added to pretreat CFsto determine the optimal con-centration.Sirius red staining was executed to observe the deposition of collagen fibres in each group.Immu-nofluorescence and Western blot were carried out to de-tect the expression ofα-SMA.Besides,Western blot was also used to detect the expression of p-GSK 3βandβ-catenin.Results Compared with normal control group,high glucose with the concentration of 25 mmol·L^-1 could significantly promote the proliferation and the transdifferentiation of CFs(P<0.01)in 24 hours,and enhance the collagen deposition as well as the ex-pression ofα-SMA,β-catenin and p-GSK 3βprotein.Compared with high glucose group,after the pretreat-ment of SalB(25μmol·L^-1)and XAV939(1μmol·L^-1),the proliferation of CFswas significantly inhib-ited(P<0.01).Meantime,the deposition of colla-gen,as well as the expression ofα-SMA,β-catenin and p-GSK 3βproteinwas decreased(P<0.01).Conclu-sions SalB can inhibit the proliferation and transdif-ferentiation of high glucose-induced CFs,which could be related to the inhibition of Wnt/β-catenin signaling pathway.
作者
王娜
隋海娟
符丽娟
WANG Na;SUI Hai-juan;FU Li-juan(Dept of Pharmacology,Basic Medical College,Jinzhou Medical University,Jinzhou Liaoning 121000,China;Dept of Pharmacy,the Second Hospital,Chaoyang City,Chaoyang Liaoning 122000,China)
出处
《中国药理学通报》
CAS
CSCD
北大核心
2020年第3期414-419,共6页
Chinese Pharmacological Bulletin
基金
辽宁省自然科学基金资助项目(No 20170540351)。