异甘草素通过调节GRB2/ERK信号通路抑制血管平滑肌细胞增殖和迁移  

Isoliquiritigenin(ISL)inhibits proliferation and migration ofvascular smooth muscle cells by regulating GRB2/ERK signaling

作　　者：秦立鹏 高雪亮[1] 高丽敏 李永章 赵家宁 Qin Li-peng;Gao Xue-liang;Gao Li-min;Li Yong-zhang;Zhao Jia-ning(Dept of Neurosurgery,Hebei Provincial Hospital of Traditional Chinese Medicine,Shijiazhuang 050011,China;Cath Lab 4,Hebei Provincial Hospital of Traditional Chinese Medicine,Shijiazhuang 050011,China;Dept of Urology,Hebei Provincial Hospital of Traditional Chinese Medicine,Shijiazhuang 050011,China;Dept of Vascular surgery,Hebei Provincial Hospital of Traditional Chinese Medicine,Shijiazhuang 050011,China)

机构地区：[1]河北省中医院神经外科,河北石家庄050011 [2]河北省中医院导管室,河北石家庄050011 [3]河北省中医院泌尿外科,河北石家庄050011 [4]河北省中医院血管外科,河北石家庄050011

出　　处：《中国药理学通报》2025年第3期543-554,共12页Chinese Pharmacological Bulletin

基　　金：河北省中医药管理局科研课题(No 2022039)。

摘　　要：目的探讨异甘草素(isoliquiritigenin,ISL)通过调节GRB2/ERK信号抑制血管平滑肌细胞(vascular smooth muscle cells,VSMCs)增殖和迁移的相关机制。方法培养人原代血管平滑肌细胞(hVSMCs),探究分别用不同浓度ISL与固定浓度的生长因子PDGF-BB、EGF进行刺激,随后通过过表达GRB2观察其对ISL作用效果的影响。CCK-8检测细胞增殖;BrdU检测DNA合成;Western blot检测OPN、ICAM-1、VCAM-1、GRB2、ERK1/2、p-ERK1/2表达水平;细胞划痕法检测细胞迁移;Transwell检测细胞侵袭。结果与空白对照组、ISL 20 mg·L^(-1)相比,PDGF-BB组、EGF组细胞活性、DNA合成上升;细胞迁移距离降低,侵袭数量上升;GRB2、p-ERK1/2上升。与PDGF-BB 40μg·L^(-1)组或EGF 10 mg·L^(-1)组相比,ISL药物干预组细胞活性、DNA合成下降;迁移细胞距离上升,侵袭细胞个数降低;GRB2、p-ERK1/2表达量下降。与ISL 20 mg·L^(-1)+PDGF-BB、ISL 20 mg·L^(-1)+EGF相比,ISL+PDGF-BB+pcDNA-GRB2组、ISL+EGF+pcDNA-GRB2组GRB2、p-ERK1/2、QPN、ICAM-1、VCAM-1、细胞活性、DNA合成上升;迁移距离降低,侵袭数量上升。与ISL+PDGF-BB+pcDNA-GRB2组、ISL+EGF+pcDNA-GRB2组相比,pcDNA-GRB2+PDGF-BB组或pcDNA-GRB2+EGF组GRB2、p-ERK1/2、OPN、ICAM-1、VCAM-1、细胞活性、DNA合成升高;迁移距离降低,侵袭数量升高。结论ISL通过调节GRB2/ERK信号通路抑制VSMCs增殖和迁移。Aim To explore the relevant mechanisms of isoliquiritigenin(ISL)in inhibiting the proliferation and migration of vascular smooth muscle cells(VSMCs)by regulating the GRB2/ERK signaling pathway.Methods Human primary vascular smooth muscle cells(hVSMCs)were cultured,and stimulated with different concentrations of ISL and fixed concentrations of growth factors PDGF-BB and EGF,respectively.Subsequently,the effect of overexpressing GRB2 on the efficacy of ISL was observed.CCK-8 assay was used to detect cell proliferation;BrdU assay was used to detect DNA synthesis;Western blot was used to detect the expression levels of OPN,ICAM-1,VCAM-1,GRB2,ERK1/2,and p-ERK1/2;wound healing assay was used to detect cell migration;transwell assay was used to detect cell invasion.Results Compared with the blank control group and the ISL 20 mg·L^(-1)group,the PDGF-BB group and the EGF group showed increased cell viability and DNA synthesis,decreased cell migration distance,and increased number of invasive cells.Additionally,the expression levels of GRB2 and p-ERK1/2 increased.Compared with the PDGF-BB 40μg·L^(-1)group or the EGF 10 mg·L^(-1)group,the ISL drug intervention group showed decreased cell viability and DNA synthesis,increased migration distance of cells,decreased number of invasive cells,and decreased expression levels of GRB2 and p-ERK1/2.Compared with the ISL 20 mg·L^(-1)+PDGF-BB and ISL 20 mg·L^(-1)+EGF groups,the groups with ISL+PDGF-BB+pcDNA-GRB2 group and ISL+EGF+pcDNA-GRB2 group showed increased expression levels of GRB2,p-ERK1/2,OPN,ICAM-1,and VCAM-1,increased cell viability and DNA synthesis,decreased migration distance,and increased number of invasive cells.Compared with the ISL+PDGF-BB+pcDNA-GRB2 group and the ISL+EGF+pcDNA-GRB2 group,the pcDNA-GRB2+PDGF-BB group or the pcDNA-GRB2+EGF group showed increased expression levels of GRB2,p-ERK1/2,OPN,ICAM-1,and VCAM-1,increased cell viability and DNA synthesis,decreased migration distance,and increased number of invasive cells.Conclusions Isoliquiritigenin inhibi

关 键 词：人原代血管平滑肌细胞 异甘草素 GRB2/ERK信号通路 迁移 增殖 作用机制 

分 类 号：R284.1[医药卫生—中药学] R322.12[医药卫生—中医学] R322.74R329.28R341