基于CX3CL1/CX3CR1轴探讨槲皮素对大鼠血管平滑肌细胞增殖的抑制作用  

Inhibitory Effect of Quercetin on the Proliferation of Rat Vascular Smooth Muscle Cells Based on CX3CL1/CX3CR1 Axis

作　　者：徐恩国 任诗佳 刘文华[1] 蔡夏叶 Xu Enguo;Ren Shijia;Liu Wenhua;Cai Xiaye(Department of Cardiology,Taizhou First People'Hospital,Zhejiang Taizhou 318020,China;Department of Dermatology,Taizhou First People'Hospital,Zhejiang Taizhou 318020,China)

机构地区：[1]台州市第一人民医院心内科,浙江台州318020 [2]台州市第一人民医院皮肤科,浙江台州318020

出　　处：《中国药师》2020年第7期1245-1249,1255,共6页China Pharmacist

基　　金：浙江省中医药科学研究基金项目(编号:2018ZB067)。

摘　　要：目的:基于人趋化因子Fractalkine(CX3CL1)/人趋化因子Fractalkine受体(CX3CR1)轴探讨槲皮素对大鼠血管平滑肌细胞(VSMC)增殖的抑制作用。方法:设VSMC细胞组、西拉普利组(100.0μg·ml^-1)、槲皮素低、高剂量组(槲皮素终浓度分别为100.0,200.0μg·ml^-1);各组每孔设6个平行样,培养72 h。培养结束后,CCK-8溶液试剂测定细胞增殖水平,结晶紫染色测定单克隆形成数目,流式细胞仪分析细胞凋亡水平,RT-PCR法及Western-Blot法测定细胞CX3CL1、CX3CR1基因和蛋白水平。结果:与VSMC细胞组比较,西拉普利组、槲皮素低、高剂量组吸光度(A)值、存活率、单克隆形成数目、CX3CL1、CX3CR 1mRNA和蛋白表达水平降低,而凋亡率升高(P<0.05)。与西拉普利组比较,槲皮素低剂量组A值、存活率、单克隆形成数目、CX3CL1、CX3CR1 mRNA和蛋白表达水平升高,而凋亡率降低(P<0.05);槲皮素高剂量组A值、存活率、单克隆形成数目、CX3CL1、CX3CR1 mRNA和蛋白表达水平降低,而凋亡率升高(P<0.05);且槲皮素高剂量组A值、存活率水平、单克隆形成数目、CX3CL1、CX3CR1 mRNA和蛋白表达水平低于槲皮素低剂量组,而凋亡率高于槲皮素低剂量组(P<0.05)。结论:在100.0~200.0μg·ml^-1的范围内,槲皮素能抑制大鼠血管平滑肌细胞增殖,促进大鼠血管平滑肌细胞凋亡;其机制可能与槲皮素能抑制大鼠血管平滑肌细胞CX3CL1、CX3CR1 mRNA和蛋白表达水平进而抑制CX3CL1/CX3CR1轴的激活有关。Objective:To investigate the inhibitory effect of quercetin on the proliferation of rat vascular smooth muscle cells based on the CX3 CL1/CX3 CR1 axis.Methods:VSMC cells group,cilazapril group(100.0μg·ml^-1),and quercetin low and high dose groups(100.0μg·ml^-1 and 200.0μg·ml^-1)were set up,and 6 parallel samples per well in each group were cultured for 72 hours.At the end of culture,CCK-8 solution reagent was used to measure the cell proliferation level,and crystal violet staining was used to measure the number of monoclonal formation,and flow cytometry was used to analyze the cell apoptosis level,and RT-PCR and Western blot were used to measure the gene and protein levels of CX3 CL1 and CX3 CR1.Results:Compared with those in VSMC group,the OD value,survival rate,number of monoclonal formation,CX3 CL1,CX3 CR1 mRNA and protein expression levels of cilazapril group and quercetin low and high dose groups were significantly decreased,while the apoptosis rate increased(P<0.05).Compared with thsoe in cilazapril group,the OD value,survival rate,number of monoclonal formation,CX3 CL1,CX3 CR1 mRNA and protein expression levels of quercetin low dose group were significantly increased,while the apoptosis decreased(P<0.05),and the level of OD,survival rate,number of monoclonal formation,and expressions of CX3 CL1,CX3 CR1 mRNA and protein in quercetin high dose group decreased,while the level of apoptosis increased(P<0.05).The level of OD,survival rate,number of monoclonal formation,and expressions of CX3 CL1,CX3 CR1 mRNA and protein in quercetin high dose group was lower than those in quercetin low dose group,while the apoptosis rate was higher than that in quercetin low dose group(P<0.05).Conclusion:Within the dose range of 100.0μg·ml^-1-200.0μg·ml^-1,quercetin can inhibit the proliferation of VSMCs and promote the apoptosis of VSMCs in rats.The mechanism may be related to the inhibition of CX3 CL1,CX3 CR1 mRNA and protein expression levels of VSMCs and the inhibition of activation of CX3 CL1/CX3 CR1 axis by querc

关 键 词：槲皮素 血管平滑肌细胞 增殖 人趋化因子Fractalkine 人趋化因子Fractalkine受体 

分 类 号：R965.1[医药卫生—药理学]