淫羊藿苷通过影响MAPK信号通路抑制ox-LDL诱导的血管平滑肌细胞增殖作用研究

Effects of icariin on proliferation of vascular smooth muscle cell induced by ox-LDL via impacting MAPK signaling pathway

研究淫羊藿苷(ICA)对氧化低密度脂蛋白(ox-LDL)诱导血管平滑肌细胞(VSMC)增殖的抑制作用,以及对增殖细胞核抗原(PCNA)表达和丝裂原活化蛋白激酶(MAPK)信号通路的影响。以ox-LDL(50 mg·L-1)诱导VSMC增殖,采用MTT法检测ICA对ox-LDL诱导VSMC增殖的抑制作用;Real-time PCR和Western blot方法检测ICA对ox-LDL诱导增殖VSMC内细胞周期相关蛋白PCNA基因及蛋白表达的影响;Western blot方法检测ICA对ox-LDL诱导增殖VSMC内p38MAPK,ERK1/2,JNK信号通路相关信号蛋白磷酸化的影响。结果显示,经ox-LDL(50 mg·L-1)刺激后,VSMC增殖活性显著增强,细胞存活率显著提升,S期、G2/M期细胞显著增加,G0/G1期细胞显著减少;同时,PCNA基因及蛋白表达水平显著提升;不同浓度的ICA(40,20,10μmol·L-1)可显著抑制ox-LDL诱导的VSMC增殖,减少S期、G2/M期细胞,增加G0/G1期细胞,降低ox-LDL诱导的PCNA基因及蛋白的表达水平,下调ox-LDL诱导的p-p38和p-ERK1/2蛋白的表达,但不影响p-JNK蛋白的表达。上述结果表明,ICA对ox-LDL诱导的VSMC增殖具有抑制作用,可能通过降低PCNA表达和阻断p38MAPK和ERK1/2信号通路抑制VSMC增殖。

This paper was aimed to study the effects of icariin（ ICA） on the proliferation of vascular smooth muscle cell（ VSMC）induced by oxidized low density lipoprotein（ ox-LDL）,and the molecular mechanism of the expression of proliferating cell nuclear antigen（ PCNA） and MAPK signaling pathway. In this study,VSMC was induced by ox-LDL（ 50 mg·L^-1）,the effect of ICA on the proliferation of VSMC was detected by MTT assay,Western blot and Real-time PCR. The results showed that after stimulation of ox-LDL,the proliferation activity of VSMC was increased,S phase,G2/M phase cells were increased,G0/G1 phase cells were decreased,PCNA protein expression was enhanced; ICA（ 40,20,10 μmol·L^-1） could effectively inhibit ox-LDL-induced VSMC proliferation,S phase and G2/M phase cells were decreased,the percentage of cells in G0/G1 phase were increased,PCNA expression was decreased,p38 MAPK and ERK1/2 activation were inhibited. These results indicate that ICA can inhibit the proliferation of VSMC by reducing the expression of PCNA and blocking the p38 MAPK and ERK1/2 signaling pathway.