五味子甲素通过MAPK/ERK途径拮抗黑素细胞中黑素生成的机制研究  

Mechanism of Schisandrin A Antagonizes Melanogenesis in Melanocytes Through MAPK/ERK Pathway

作　　者：叶峻宏 韩宪伟[2] 吕雯 戴晓宇 杨先旭 杨洁 张明 陈贤祯[3] YE Junhong;HAN Xianwei;LYU Wen;DAI Xiaoyu;YANG Xianxu;YANG Jie;ZHANG Ming;CHEN Xianzhen(Dept.of Dermatology,the Fifth People’s Hospital of Hainan,Haikou 570206,China;Dept.of Dermatology,the Seventh People’s Hospital of Shenyang,Shenyang 110003,China;Dept.of Dermatology,Sir Run Run Shaw Hospital,Zhejiang University School of Medicine,Hangzhou 310000,China)

机构地区：[1]海南省第五人民医院皮肤科,海口570206 [2]沈阳市第七人民医院皮肤科,沈阳110003 [3]浙江大学医学院附属邵逸夫医院皮肤科,杭州310000

出　　处：《中国医院用药评价与分析》2022年第10期1184-1188,共5页Evaluation and Analysis of Drug-use in Hospitals of China

基　　金：辽宁省自然科学基金项目(No.2021-MS-368);浙江省医药卫生科技计划项目(No.2017ZD004)。

摘　　要：目的:探讨五味子甲素通过丝裂原激活的蛋白激酶(MAPK)/胞外信号调节激酶(ERK)途径拮抗黑素细胞中黑素生成的机制。方法:设人表皮黑素细胞组,五味子甲素低、中及高剂量组(125、250及500μmol/mL)。培养结束后,采用噻唑蓝法测定细胞活力,流式细胞仪评估细胞凋亡指数,黑素制备标准曲线测定黑色素合成能力,酶联免疫吸附试验测定酪氨酸酶水平,逆转录聚合酶链反应及蛋白质印迹法测定细胞MAPK、ERK mRNA和蛋白表达水平。结果:与人表皮黑素细胞组比较,五味子甲素低、中及高剂量组的吸光度(OD)值、存活率、黑素合成水平和酪氨酸酶水平均降低,差异均有统计学意义(P<0.05);且随着五味子甲素剂量的升高,人表皮黑素细胞OD值、存活率、黑素合成水平和酪氨酸酶水平逐渐降低,五味子甲素各剂量组呈剂量-效应趋势(P<0.05)。与人表皮黑素细胞组比较,五味子甲素低、中及高剂量组细胞凋亡率,MAPK、ERK mRNA和蛋白表达水平升高,差异均有统计学意义(P<0.05);且随着五味子甲素剂量的升高,人表皮黑素细胞凋亡率,MAPK、ERK mRNA和蛋白表达水平逐渐升高,五味子甲素各剂量组呈剂量-效应趋势(P<0.05)。结论:五味子甲素能抑制黑素细胞增殖,促进黑素细胞凋亡,进而抑制黑素生成;其机制可能与五味子甲素促进人表皮黑素细胞MAPK、ERK mRNA和蛋白表达,进而激活MAPK/ERK途径有关。OBJECTIVE: To probe into the mechanism of schisandrin A antagonizes melanogenesis in melanocytes through mitogen-activated protein kinase(MAPK)/extracellular signal-regulated kinase(ERK) pathway. METHODS: The human epidermal melanocyte group, schizandrin A low, medium and high dose group(125, 250, 500 μmol/mL) were set up. After incubation, cell viability was measured by MTT method, apoptosis indicators were evaluated by flow cytometry, and melanin preparation standard curve was used to measure melanin synthesis ability, enzyme linked immunosorbent assay was used to measure the level of tyrosinase, the mRNA and protein expression levels of MAPK and ERK were determined by reverse transcription-polymerase chain reaction and Western blotting. RESULTS: Compared with the human epidermal melanocyte group, the OD value, survival rate, melanin synthesis level and tyrosinase level of schizandrin A low, medium and high dose group decreased, with statistically significant differences(P<0.05). With the increasing dose of schizandrin A, the OD value, survival rate, melanin synthesis level and tyrosinase level of human epidermal melanocytes decreased, and the effect of each dose group of schisandrin A showed the dose-effect trend(P<0.05). Compared with the human epidermal melanocyte group, the apoptotic rate, the mRNA and protein expression levels of MAPK, ERK in the schisandrin A low, medium and high dose group increased, with statistically significant differences(P<0.05). With the increasing dose of schizandrin A, the apoptosis rate, the mRNA and protein expression levels of MAPK, ERK of human epidermal melanocytes increased, and the effects of each dose group of schisandrin A showed the dose-effect trend(P<0.05). CONCLUSIONS: Schizandrin A can inhibit the proliferation of melanocytes, promote the apoptosis of melanocytes, and then inhibit the melanogenesis. Its mechanism may be related to the activation of MAPK/ERK pathway by promoting the mRNA and protein expression levels of MAPK and ERK in human epidermal melanocytes by

关 键 词：五味子甲素 丝裂原激活的蛋白激酶/胞外信号调节激酶途径 黑素细胞 黑素生成 

分 类 号：R96[医药卫生—药理学]