系统ALA-PDT治疗寻常性银屑病动物模型的疗效观察及机制探讨
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摘要
目的观察系统5-氨基酮戊酸-光动力疗法(ALA-PDT)对寻常性银屑病动物模型的疗效,并初步探讨其作用机制。方法 18只银屑病模型小鼠随机分为三组:ALA-PDT组、ALA组和红光组(RL),治疗1次/周,共2次。观察耳部皮损并进行评分;2周后,取下鼠耳组织进行HE染色,观察病理表现,并采用流式细胞术检测皮损中γδT细胞数量,采用实时定量PCR检测皮损中炎症因子IL-17、IL-6、INF-γ和TNF-α的表达水平。结果 2周后,ALA-PDT组皮损严重程度较ALA组和RL组明显降低,差异有统计学意义(P均<0.05);较ALA组及RL组,ALA-PDT组皮损表皮厚度变薄,炎症细胞浸润明显减少;ALA-PDT组皮损中γδT细胞数量与ALA组及RL组相比显著降低(P均<0.000 1);ALA-PDT组皮损中IL-17A、IL-6、INF-γ和TNF-αmRNA表达水平较ALA组和RL组均明显降低,差异有统计学意义(P均<0.01)。结论系统ALA-PDT改善了银屑病模型小鼠的皮损情况;系统ALA-PDT治疗银屑病模型小鼠的作用机制可能与其减轻了皮损中炎症细胞的浸润并且下调了相关炎症因子的表达水平有关。
Objective To investigate the efficacy and mechanism of systemic photodynamic therapy with 5-aminolaevulinic acid(ALA-PDT) for psoriasis vulgaris in a mouse model.Methods Eighteen K14-VEGF transgenic mice were randomly divided into three groups: ALA-PDT,ALA and red light(RL) groups.Three groups were treated once a week for two times.The lesions were evaluated during the study period.After two weeks of treatment, ears were collected for HE staining and flow cytometry γδ T cells.Real-time quantitative PCR was used to measure expression of mRNA for IL-17,IL-6,INF-γ and TNF-α.Results The severity of psoriatic lesions in ALA-PDT group was significantly lower than that in ALA and RL groups(P<0.05).The average epidermal thickness of ALA-PDT group was thinner than that of ALA and RL groups.ALA-PDT treatment decreased infiltration of inflammatory cells in comparison to other groups.Number of γδ T cells in psoriatic lesions also decreased in ALA-PDT group in comparison to ALA and RL groups(P<0.000 1).Compared to ALA group and RL group,the mRNA levels of IL-17 A,IL-6,INF-γ and TNF-α were significantly reduced in ALA-PDT group(P<0.01).Conclusion Systemic ALA-PDT can alleviate psoriasis in the mouse model, possibly via inhibition of inflammatory infiltration and expression of inflammatory cytokines.
Objective To investigate the efficacy and mechanism of systemic photodynamic therapy with 5-aminolaevulinic acid(ALA-PDT) for psoriasis vulgaris in a mouse model.Methods Eighteen K14-VEGF transgenic mice were randomly divided into three groups: ALA-PDT,ALA and red light(RL) groups.Three groups were treated once a week for two times.The lesions were evaluated during the study period.After two weeks of treatment, ears were collected for HE staining and flow cytometry γδ T cells.Real-time quantitative PCR was used to measure expression of mRNA for IL-17,IL-6,INF-γ and TNF-α.Results The severity of psoriatic lesions in ALA-PDT group was significantly lower than that in ALA and RL groups(P<0.05).The average epidermal thickness of ALA-PDT group was thinner than that of ALA and RL groups.ALA-PDT treatment decreased infiltration of inflammatory cells in comparison to other groups.Number of γδ T cells in psoriatic lesions also decreased in ALA-PDT group in comparison to ALA and RL groups(P<0.000 1).Compared to ALA group and RL group,the mRNA levels of IL-17 A,IL-6,INF-γ and TNF-α were significantly reduced in ALA-PDT group(P<0.01).Conclusion Systemic ALA-PDT can alleviate psoriasis in the mouse model, possibly via inhibition of inflammatory infiltration and expression of inflammatory cytokines.
引文
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[7] 张力文,李艳嫦,刘冬先.寻常性银屑病患者皮损组织中RORγt,IL-17,Foxp3和IL-10的检测[J].中国皮肤性病学杂志,2014,28(7):681-683.
[8] Cohen BE,Kerner M,Rozenman D,et al.Combination therapy of cyclosporine and anti-tumor necrosis factor alpha in psoriasis:a case series of 10 patients[J].Dermatol Ther,2015,28(3):126-130.
[9] Piaserico S,Sandini E,Saldan A,et al.Effects of TNF-alpha inhibitors on circulating Th17 cells in patients affected by severe psoriasis[J].Drug Dev Res,2014,75(Suppl 1):S73-76.
[10] Croxford AL,Karbach S,Kurschus FC,et al.IL-6 regulates neutrophil microabscess formation in IL-17A-driven psoriasiform lesions[J].J Invest Dermatol,2014,134(3):728-735.
[11] Cai Y,Xue F,Fleming C,et al.Differential developmental requirement and peripheral regulation for dermal Vγ4 and Vγ6T17 cells in health and inflammation[J].Nat Commun,2014,5:3986.
[12] Bissonnette R,Zeng H,McLean DI,et al.Oral aminolevulinic acid induces protoporphyrin IX fluorescence in psoriatic plaques and peripheral blood cells[J].Photochem Photobiol,2001,74(2):339-345.
[2] Tandon YK,Yang MF,Baron ED.Role of photodynamic therapy in psoriasis:a brief review[J].Photodermatol Photoimmunol Photomed,2008,24(5):222-230.
[3] Bissonnette R,Tremblay JF,Juzenas P,et al.Systemic photodynamic therapy with aminolevulinic acid induces apoptosis in lesional T lymphocytes of psoriatic plaques[J].J Invest Dermatol,2002,119(1):77-83.
[4] Yan HX,Li WW,Zhang Y,et al.Accumulation of FLT3(+) CD11c (+) dendritic cells in psoriatic lesions and the anti-psoriatic effect of a selective FLT3 inhibitor[J].Immunol Res,2014,60(1):112-126.
[5] Canavese M,Altruda F,Ruzicka T,et al.Vascular endothelial growth factor (VEGF) in the pathogenesis of psoriasis-a possible target for novel therapies?[J].J Dermatol Sci,2010,58(3):171-176.
[6] Campanati A,Orciani M,Consales V,et al.Characterization and profiling of immunomodulatory genes in resident mesenchymal stem cells reflect the Th1-Th17/Th2 imbalance of psoriasis[J].Arch Dermatol Res,2014,306(10):915-920.
[7] 张力文,李艳嫦,刘冬先.寻常性银屑病患者皮损组织中RORγt,IL-17,Foxp3和IL-10的检测[J].中国皮肤性病学杂志,2014,28(7):681-683.
[8] Cohen BE,Kerner M,Rozenman D,et al.Combination therapy of cyclosporine and anti-tumor necrosis factor alpha in psoriasis:a case series of 10 patients[J].Dermatol Ther,2015,28(3):126-130.
[9] Piaserico S,Sandini E,Saldan A,et al.Effects of TNF-alpha inhibitors on circulating Th17 cells in patients affected by severe psoriasis[J].Drug Dev Res,2014,75(Suppl 1):S73-76.
[10] Croxford AL,Karbach S,Kurschus FC,et al.IL-6 regulates neutrophil microabscess formation in IL-17A-driven psoriasiform lesions[J].J Invest Dermatol,2014,134(3):728-735.
[11] Cai Y,Xue F,Fleming C,et al.Differential developmental requirement and peripheral regulation for dermal Vγ4 and Vγ6T17 cells in health and inflammation[J].Nat Commun,2014,5:3986.
[12] Bissonnette R,Zeng H,McLean DI,et al.Oral aminolevulinic acid induces protoporphyrin IX fluorescence in psoriatic plaques and peripheral blood cells[J].Photochem Photobiol,2001,74(2):339-345.
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