青蒿素改善咪喹莫特诱导银屑病样小鼠的作用研究  

Study on the effects of artemisinin in improving imiquimod-induced psoriasis-like mice

作　　者：岑雯[1] 马彦[1] 贾晓强[1] CEN Wen;MA Yan;JIA Xiao-qiang(Department of Dermatology and Venereology,The Second Hospital of Shanxi Medical University,Taiyuan 030000,Shanxi Province,China)

机构地区：[1]山西医科大学第二医院皮肤性病科,山西太原030000

出　　处：《中国临床药理学杂志》2024年第21期3136-3141,共6页The Chinese Journal of Clinical Pharmacology

摘　　要：目的研究青蒿素通过调控微小RNA-129-5p(miRNA-129-5p)/钙/钙调蛋白依赖性蛋白激酶Ⅳ(CaMK4)轴介导信号转导及转录激活因子3(STAT3)信号通路对银屑病样小鼠的影响。方法将所有小鼠随机分为对照组(正常饲养)、模型组(0.9%NaCl)、阳性对照组(1 mg·kg^(-1)甲氨蝶呤)、实验组(100 g·mL^(-1)青蒿素)、miR-129-5p inhibitor组(在实验组的基础上尾静脉注射miR-129-5p inhibitor)、siCaMK4组(在实验组的基础上尾静脉注射siCaMK4)。除对照组外,其余各组小鼠均用咪喹莫特构建银屑病模型。用实时荧光定量聚合酶链反应法检测miR-129-5p、CaMK4 mRNA的相对表达水平,用双荧光素酶报告基因法验证miR-129-5p与CaMK4的靶向关系,用银屑病面积与严重性指数评分(PASI)评估皮损情况,用酶联免疫吸附试验法检测白细胞介素-17(IL-17)、IL-23、IL-22的水平,用蛋白质印迹法检测STAT3通路蛋白的相对表达水平。结果对照组、模型组和实验组的miR-129-5p相对表达水平分别为1.00±0.18、0.54±0.07和0.88±0.13,CaMK4 mRNA相对表达水平分别为1.00±0.17、1.68±0.31和1.20±0.22;对照组、模型组、阳性对照组、实验组、miR-129-5p inhibitor组和siCaMK4组的第7天PASI分别为0、(10.20±1.22)、(7.20±0.68)、(6.30±0.66)、(7.50±0.88)和(4.80±0.63)分,IL-17表达水平分别为(1.89±0.19)、(3.56±0.38)、(2.22±0.28)、(2.55±0.33)、(3.19±0.41)和(1.99±0.22)pg·mL^(-1),IL-23表达水平分别为(4.48±0.61)、(6.28±0.77)、(5.22±0.51)、(5.33±0.61)、(6.01±0.66)和(4.64±0.55)pg·mL^(-1),IL-22表达水平分别为(5.14±0.68)、(7.84±0.87)、(5.86±0.66)、(5.99±0.62)、(6.88±0.73)和(5.22±0.60)pg·mL^(-1),p-STAT3/STAT3比值分别为0.38±0.04、0.68±0.07、0.45±0.05、0.48±0.05、0.57±0.07和0.42±0.04。模型组的上述指标与对照组比较,阳性对照组、实验组的上述指标与模型组比较,miR-129-5p inhibitor组、siCaMK4组的上述指标与实验组比较,在统计学上差异均有�Objective To investigate the effect of artemisinin on signal transducer and activator of transcription 3(STAT3)signalling pathway in psoriasis-like mice through modulation of microRNA-129-5p(miRNA-129-5p)/calcium/calmodulin-dependent protein kinaseⅣ(CaMK4)axis-mediated signal transduction and activator of transcription factor 3(STAT3)signalling pathway in psoriasis-like mice.Methods All mice were randomly divided into control group(normal feeding),model group(0.9%NaCl),positive control group(1 mg·kg^(-1)methotrexate),experimental group(100 g·mL^(-1)artemisinin),miR-129-5p inhibitor group(miR-129-5p inhibitor was injected into the tail vein on the basis of the experimental group),siCaMK4 group(siCaMK4 was injected into the tail vein on the basis of the experimental group).Except for the control group,the mice in each group were treated with imiquimod to construct a psoriasis model.Real-time fluorescence quantitative polymerase chain reaction(qRT-PCR)was used to detect miR-129-5p and CaMK4 mRNA relative expression;dual luciferase reporter gene assay was used to verify the targeting of miR-129-5p and CaMK4.Psoriasis area and severity index(PASI)were used to assess skin lesions;enzyme-linked immunosorbent assay(ELISA)was used to detect interleukin-17(IL-17),IL-23,IL-22 levels;Western blot were used to detect the STAT3 pathway protein expression.Results The miR-129-5p relative expression levels were 1.00±0.18,0.54±0.07,0.88±0.13;CaMK4 mRNA relative expression levels were 1.00±0.17,1.68±0.31,1.20±0.22 in the control,model,and experimental groups,respectively.The 7th day PASIs of the control,model,positive control,experimental,miR-129-5p inhibitor group,and siCaMK4 group were 0,(10.20±1.22),(7.20±0.68),(6.30±0.66),(7.50±0.88),and(4.80±0.63)scores,respectively;the expression levels of IL-17 were(1.89±0.19),(3.56±0.38),(2.22±0.28),(2.55±0.33),(3.19±0.41),(1.99±0.22)pg·mL^(-1),respectively;IL-23 expression levels were(4.48±0.61),(6.28±0.77),(5.22±0.51),(5.33±0.61),(6.01±0.66),(4.64±0.55)pg·mL^(

关 键 词：青蒿素 银屑病 微小RNA-129-5p 钙/钙调蛋白依赖性蛋白激酶Ⅳ 信号转导及转录激活因子3 

分 类 号：R28[医药卫生—中药学]