寻常性银屑病患者外周血STAT3、IL-4mRNA的表达与白芍总苷治疗前后的变化
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摘要
目的:探讨信号转导及转录激活因子(STAT)3、白介素(IL)-4 mRNA在寻常性银屑病(PV)患者外周血的表达及其与银屑病皮损面积和严重程度指数(PASI)的相关性,探讨白芍总苷(TGP)对PV的治疗作用。方法:采用实时荧光定量反转录聚合酶链式反应(RT-PCR)检测健康对照组和TGP治疗前后PV患者外周血STAT3及IL-4 mRNA的表达量,并分析其与PASI的相关性。结果:PV患者外周血中STAT3及IL-4 mRNA的表达量高于健康对照组,STAT3 mRNA的表达量差异有统计学意义(P<0.05),IL-4 mRNA的表达量差异无统计学意义(P>0.05);患者外周血中STAT3和IL-4 mRNA表达无相关性(r=-0.183,P>0.05);PASI与患者外周血中STAT3 mRNA的表达呈正相关(r=-0.320,P<0.05),与IL-4 mRNA的表达无相关性(r=0.097,P>0.05)。经TGP治疗1个月和2个月后,46例患者外周血STAT3 mRNA的表达量和PASI评分均较治疗前降低(P<0.05),IL-4mRNA的表达量较治疗前升高(P<0.05)。结论:STAT3可能参与了PV的发病过程,IL-4在PV中作用不明显,TGP在治疗PV中起较大作用。
Objective: To investigate the mRNA expression levels of signal transducer and activator of transcription(STAT)3, and interleukin(IL)-4 in peripheral blood of patients with psoriasis vulgaris(PV), and their correlation with psoriasis area and severity index(PASI). The therapeutic effect of total glucosides of penoy(TGP) for psoriasis was also assessed.Methods: Real-time fluorescence quantitative reverse transcription polymerase chain reaction(RT-PCR) was performed to detect the expression levels of STAT3 and IL-4 mRNA in peripheral blood of normal controls and patients with PV before and after the treatment with TGP. The correlation of STAT3 and IL-4 mRNA levels with PASI was also analyzed. Results: The expression levels of STAT3 were higher in PV group than in normal controls(P<0.05). But IL-4 mRNA levels did not differ significantly between PV and normal controls. No correlation between STAT3 and IL-4 expression was found in peripheral blood of patients with PV(r=-0.183, P>0.05). PASI was positively correlated with STAT3 mRNA expression in PV patients(r=-0.320, P<0.05) while there was no correlation between PASI and IL-4(r=0.097, P>0.05). After a month and two months of treatment with TGP, the expression levels of STAT3 mRNA and PASI scores decreased significantly in PV patients.In contrast, the expression levels of IL-4 mRNA increased following TGP treatment(P<0.05). Conclusions: STAT3, not IL-4,might be involved in the pathogenesis of PV. TGP is effective for PV.
Objective: To investigate the mRNA expression levels of signal transducer and activator of transcription(STAT)3, and interleukin(IL)-4 in peripheral blood of patients with psoriasis vulgaris(PV), and their correlation with psoriasis area and severity index(PASI). The therapeutic effect of total glucosides of penoy(TGP) for psoriasis was also assessed.Methods: Real-time fluorescence quantitative reverse transcription polymerase chain reaction(RT-PCR) was performed to detect the expression levels of STAT3 and IL-4 mRNA in peripheral blood of normal controls and patients with PV before and after the treatment with TGP. The correlation of STAT3 and IL-4 mRNA levels with PASI was also analyzed. Results: The expression levels of STAT3 were higher in PV group than in normal controls(P<0.05). But IL-4 mRNA levels did not differ significantly between PV and normal controls. No correlation between STAT3 and IL-4 expression was found in peripheral blood of patients with PV(r=-0.183, P>0.05). PASI was positively correlated with STAT3 mRNA expression in PV patients(r=-0.320, P<0.05) while there was no correlation between PASI and IL-4(r=0.097, P>0.05). After a month and two months of treatment with TGP, the expression levels of STAT3 mRNA and PASI scores decreased significantly in PV patients.In contrast, the expression levels of IL-4 mRNA increased following TGP treatment(P<0.05). Conclusions: STAT3, not IL-4,might be involved in the pathogenesis of PV. TGP is effective for PV.
引文
[1]王刚.银屑病研究热点[J].中华皮肤科杂志,2013,46(3):153-156.
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[7]Kagami S,Rizzo HL,Lee JJ,et al.Circulating Th17,Th22,and Th1 cells are increased in psoriasis[J].J Invest Dermatol,2010,130(5):1373-1383.
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[9]Zheng XF,Sun YD,Liu XY.Correlation of expression of STAT3,VEGF and differentiation of Th17 cells in psoriasis vulgaris of guinea pig[J].Asian Pac J Trop Med,2014,7(4):313-316.
[10]Al Khatib S,Keles S,Garcia Lloret M,et al.Defects along the Th17 differentiation pathway underlie genetically distinct forms of the hyper Ig E syndrome[J].J Allergy Clin Immunol,2009,124(2):342-348.
[11]Yang F,Wu WF,Yan YL,et al.Expression of IL-23/Th17pathway in a murine model of Coxsackie virus B3-induced viralmyocarditis[J].Virol J,2011,14(8):301-309.
[12]苏彤,陈宏,李璐,等.寻常性银屑病患者外周血白介素17、白介素23 m RNA的表达及与病情相关性研究[J].中华皮肤科杂志2014,47(4):278-281.
[13]Miyoshi K,Takaishi M,Nakajima K.Stat3 as a therapeutic target for the treatment of psoriasis:a clinical feasibility study with STA-21,a Stat3 inhibitor[J].J Invest Dermatol,2011,131(1):108-117.
[14]冯世军,高顺强,李华蕊,等.寻常性银屑病皮损中Stat3和Survivin的表达及相关性分析[J].河北医药,2012,34(2):165-167.
[15]Coimbra S,Figueiredo A,Castro E,et al.The roles of cells and cytokines in the pathogenesis of psoriasis[J].Int J Dermatol,2012,51(4):389-395.
[16]黎静宜,郭在培,李薇.窄谱中波紫外线对寻常性银屑病患者血清和皮损中IFN-γ,IL-4的影响[J].中国皮肤性病学杂志,2008,22(4):214-216.
[17]Lin J,Xiao L,Ouyang G,et al.Total glucosides of paeony inhibits Th1/Th17 cells via decreasing dendritic cells activation in rheumatoid arthritis[J].Cell Immunol,2012,280(2):156-163.
[18]Ghoreschi K,Thomas P,Breit S,et al.Interleukin-4 therapy of psoriasis induces Th2 responses and improves human autoimmune disease[J].Nat Med,2003,1(9):40-45.
[19]黄敬文,邹国良,张士岭,等.二妙散对小鼠银屑病样模型细胞因子IFN-γ,IL-4的影响[J].中医药学报,2013,41(4):96-98.
[2]Lascorz J,Hüffmeier U,Schulze-Koops H,et al.Lack of genetic association of the interleukin-4 receptor single-nucleotide polymorphisms I50V and Q551R with erosive disease in psoriatic[J].Arthritis Rheum,2006,54(12):4023-4024.
[3]陈飚,孙乐栋,张丽,等.银屑病患者Jak/STAT信号传导通路基因表达的研究[J].皮肤性病诊疗学杂志,2013,20(01):15-18.
[4]Lima EA,Lima MMDA,Marques CDL,et al.Peroxisome proliferator-activated receptor agonists(PPARs):a promising prospect in the treatment of psoriasis and psoriatic arthritis[J].An Bras Dermatol,2013,88(6):1029-1035.
[5]Rossi A,Mandel VD,Garelli V,et al.Videodermoscopy scalp psoriasis severity index(VSCAPSI):a useful tool for evaluation of scalp psoriasis[J].Eur J Dermatol,2011,21(4):546-551.
[6]Cai Y,Fleming C,Yan J.New insights of T cells in the pathogenesis of psoriasis[J].Cell Mol Immunol,2012,9(4):302-309.
[7]Kagami S,Rizzo HL,Lee JJ,et al.Circulating Th17,Th22,and Th1 cells are increased in psoriasis[J].J Invest Dermatol,2010,130(5):1373-1383.
[8]冉立伟,兰东,贾红侠.寻常性银屑病皮损中STAT3的表达及磷酸化STAT3的水平[J].中国皮肤性病学杂志,2011,25(9):675-677.
[9]Zheng XF,Sun YD,Liu XY.Correlation of expression of STAT3,VEGF and differentiation of Th17 cells in psoriasis vulgaris of guinea pig[J].Asian Pac J Trop Med,2014,7(4):313-316.
[10]Al Khatib S,Keles S,Garcia Lloret M,et al.Defects along the Th17 differentiation pathway underlie genetically distinct forms of the hyper Ig E syndrome[J].J Allergy Clin Immunol,2009,124(2):342-348.
[11]Yang F,Wu WF,Yan YL,et al.Expression of IL-23/Th17pathway in a murine model of Coxsackie virus B3-induced viralmyocarditis[J].Virol J,2011,14(8):301-309.
[12]苏彤,陈宏,李璐,等.寻常性银屑病患者外周血白介素17、白介素23 m RNA的表达及与病情相关性研究[J].中华皮肤科杂志2014,47(4):278-281.
[13]Miyoshi K,Takaishi M,Nakajima K.Stat3 as a therapeutic target for the treatment of psoriasis:a clinical feasibility study with STA-21,a Stat3 inhibitor[J].J Invest Dermatol,2011,131(1):108-117.
[14]冯世军,高顺强,李华蕊,等.寻常性银屑病皮损中Stat3和Survivin的表达及相关性分析[J].河北医药,2012,34(2):165-167.
[15]Coimbra S,Figueiredo A,Castro E,et al.The roles of cells and cytokines in the pathogenesis of psoriasis[J].Int J Dermatol,2012,51(4):389-395.
[16]黎静宜,郭在培,李薇.窄谱中波紫外线对寻常性银屑病患者血清和皮损中IFN-γ,IL-4的影响[J].中国皮肤性病学杂志,2008,22(4):214-216.
[17]Lin J,Xiao L,Ouyang G,et al.Total glucosides of paeony inhibits Th1/Th17 cells via decreasing dendritic cells activation in rheumatoid arthritis[J].Cell Immunol,2012,280(2):156-163.
[18]Ghoreschi K,Thomas P,Breit S,et al.Interleukin-4 therapy of psoriasis induces Th2 responses and improves human autoimmune disease[J].Nat Med,2003,1(9):40-45.
[19]黄敬文,邹国良,张士岭,等.二妙散对小鼠银屑病样模型细胞因子IFN-γ,IL-4的影响[J].中医药学报,2013,41(4):96-98.