清肝凉血解毒方和凉血活血方对咪喹莫特诱导银屑病样小鼠行为学及神经肽Y表达影响
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摘要
目的:观察清肝凉血解毒方(QGLXJD)、凉血活血方(LXHX)对咪喹莫特诱导的银屑病样小鼠行为学及神经肽Y(NPY)表达的影响。方法:30只BALB/c雄性小鼠,剔除背部毛发,随机分为空白对照组(C)、模型组(M)、清肝凉血解毒方组(QG)、凉血活血方组(LX)和甲氨蝶呤组(MTX)。背部涂抹5%咪喹莫特乳膏(IMQ)诱导皮肤银屑病样模型。采用银屑病皮损面积和疾病严重程度(Psoriasis area and severity index,PASI)每日进行评分,分别运用旷场及高架十字迷宫评价各组小鼠行为学差异,HE染色后光镜下测量表皮厚度;免疫组化法检测皮损中T淋巴细胞表面标志CD3+及表皮中增殖细胞核抗原(PCNA)表达情况;采用实时PCR技术检测皮损中IL-23、IL-1β、IL-12 mRNA表达水平;Western blot法检测皮损中NPY蛋白表达情况。结果:与C组相比,M组表皮厚度、PCNA、CD3+T细胞、IL-1β、IL-12、IL-23 mRNA表达均增加(P<0.05);其余组与M组相比,表皮薄,PCNA、CD3+T细胞、IL-1β、IL-12、IL-23 mRNA表达水平均降低(P<0.05)。与C组比较,银屑病样小鼠焦虑水平高,以M组最为明显;QG组与M组比较,焦虑水平低,而LX组与QG组比较,焦虑水平高;NPY在M组中表达最多,在LX、QG、C组表达依次减少。结论:清肝凉血解毒方能改善银屑病样小鼠的焦虑行为,下调NPY的表达水平,从整体角度改善小鼠银屑病样皮损。
Objectives:To observe the effects of Qinggan Liangxue Jiedu(QGLXJD)Decoction and Liangxue Huoxue(LXHX)Decoction on behavior and the expression of neuropeptide Y in psoriatic mice induced by imiquimod. Methods:30 male BALB/c mice were randomly divided into blank control group,model group,QGLXJD group(QG),LXHX group(LX)and MTX group. The skin psoriasis model was induced by applying 5% imiquimod cream(IMQ)on the back. The psoriasis skin lesion area and severity index(PASI)were used for daily scoring,and the behavioral differences of mice in each group were evaluated by using the open-field and elevated plus maze(EPM)respectively. The thickness of the epidermis was measured under the light microscope after HE staining. The expression of CD3+ T cells and PCNA were detected by immunohistochemistry. Meanwhile,we used real-time PCR to detect the expression levels of IL-23,IL-1β,and IL-12 mRNA,Western blot to NPY protein in skin lesions. Results:Compared with group C,the epidermal thickness,PCNA,CD3+ T cells,IL-1β,IL-12,and IL-23 mRNA expression in group M were all increased(P<0.05). Compared with the M group,the epidermis was thinner,and the expression levels of PCNA,CD3+ T cells,IL-1β,IL-12,and IL-23 mRNA were all decreased(P<0.05). Compared with group C,the anxiety level of psoriatic mice was higher,which was most obvious in group M. The anxiety level was low in the QG group compared with the M group,while the anxiety level was higher in the LX group compared with the QG group. NPY was highest in group M,and decreased in group LX,QG and C. Conclusion:QGLXJD Decoction can improve the anxious behavior of psoriatic mice,down-regulate the expression level of NPY,and improve the psoriatic skin lesions of mice from the overall perspective.
Objectives:To observe the effects of Qinggan Liangxue Jiedu(QGLXJD)Decoction and Liangxue Huoxue(LXHX)Decoction on behavior and the expression of neuropeptide Y in psoriatic mice induced by imiquimod. Methods:30 male BALB/c mice were randomly divided into blank control group,model group,QGLXJD group(QG),LXHX group(LX)and MTX group. The skin psoriasis model was induced by applying 5% imiquimod cream(IMQ)on the back. The psoriasis skin lesion area and severity index(PASI)were used for daily scoring,and the behavioral differences of mice in each group were evaluated by using the open-field and elevated plus maze(EPM)respectively. The thickness of the epidermis was measured under the light microscope after HE staining. The expression of CD3+ T cells and PCNA were detected by immunohistochemistry. Meanwhile,we used real-time PCR to detect the expression levels of IL-23,IL-1β,and IL-12 mRNA,Western blot to NPY protein in skin lesions. Results:Compared with group C,the epidermal thickness,PCNA,CD3+ T cells,IL-1β,IL-12,and IL-23 mRNA expression in group M were all increased(P<0.05). Compared with the M group,the epidermis was thinner,and the expression levels of PCNA,CD3+ T cells,IL-1β,IL-12,and IL-23 mRNA were all decreased(P<0.05). Compared with group C,the anxiety level of psoriatic mice was higher,which was most obvious in group M. The anxiety level was low in the QG group compared with the M group,while the anxiety level was higher in the LX group compared with the QG group. NPY was highest in group M,and decreased in group LX,QG and C. Conclusion:QGLXJD Decoction can improve the anxious behavior of psoriatic mice,down-regulate the expression level of NPY,and improve the psoriatic skin lesions of mice from the overall perspective.
引文
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[2]张建中.银屑病的流行病学与危险因素[J].实用医院临床杂志,2013,10(1):4-6.
[3]Aleem D,Tohid H.Pro-inflammatory Cytokines,Biomarkers,Genetics and the Immune System:A Mechanistic Approach of Depression and Psoriasis[J].Rev Colomb Psiquiatr,2018,47(3):177-186.
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[6]饶俊昌,龚爱华.银屑病患者的焦虑、抑郁的精神状态及行为特点[J].中国健康心理学杂志,2017(5):677-680.
[7]张强.北方汉族银屑病患者心理健康状况调查[J].世界最新医学信息文摘,2016,16(52):229-230.
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[9]郝建侠,吴筱娟,赵梦秋,等.心理护理干预对改善银屑病患者焦虑抑郁状态的影响[J].护理实践与研究,2017(11):251.
[10]许静芳,林贤娜,张璇君,等.心理干预对银屑病患者焦虑抑郁情绪的影响[J].吉林医学,2015,36(4):747-748.
[11]王聪敏,李海涛,余明莲,等.心理护理对银屑病患者心理状态的影响[J].实用皮肤病学杂志,2014,7(2):138-139.
[12]刘艳,路永红,黄晶,等.系统性心理行为干预与药物联合治疗银屑病的研究[J].四川医学,2012,33(10):1736-1738.
[13]刘巧,吴伟伟,王爱民,等.系统性心理行为干预对银屑病患者影响的研究[J].中国中西医结合皮肤性病学杂志,2011,10(1):56-58.
[14]张剑,邓永琼,杨茜,等.杨文信从肝论治寻常型银屑病经验[J].河南中医,2012,32(9):1129-1130.
[15]李咏梅.从肝论治银屑病临床撷英--师从顾氏外科传人马绍尧教授临床经验总结[C]//中华中医药学会学术会议,国家中医药管理局继续教育项目--银屑病中医药防治交流会暨赵炳南学术思想高级研修班资料.北京:中华中医药学会,2011.
[16]徐文俊,毛常亮,冯仁洋,等.凉血活血汤对寻常型银屑病进展期患者外周血Th17相关因子的干预作用[J].中国麻风皮肤病杂志,2018,34(1):45-47.
[17]刘欣,李萍,赵京霞,等.凉血活血胶囊全方及拆方对Jurkat T淋巴细胞增殖、活化及释放细胞因子的影响[J].中国实验方剂学杂志,2012,18(22):198-202.
[18]底婷婷,赵京霞,王燕,等.凉血活血胶囊对咪喹莫特诱导小鼠银屑病样皮损的干预作用[J].中国病理生理杂志,2012,28(4):718-722.
[19]黄继汉,黄晓晖,陈志扬,等.药理试验中动物间和动物与人体间的等效剂量换算[J].中国临床药理学与治疗学,2004,9(9):1069-1072.
[20]van der Fits L,Mourits S,Voerman J S,et al.Imiquimodinduced psoriasis-like skin inflammation in mice is mediated via the IL-23/IL-17 axis[J].J Immunol,2009,182(9):5836-5845.
[21]Parisi R,Symmons D P,Griffiths C E,et al.Global epidemiology of psoriasis:a systematic review of incidence and prevalence[J].J Invest Dermatol,2013,133(2):377-385.
[22]Deng Y,Chang C,Lu Q.The Inflammatory Response in Psoriasis:a Comprehensive Review[J].Clin Rev Allergy Immunol,2016,50(3):377-389.
[23]Nair R P,Duffin K C,Helms C,et al.Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaBpathways[J].Nat Genet,2009,41(2):199-204.
[24]Taracanova A,Theoharides T.Substance P and IL-33Synergistically Stimulate Mast Cells to Release IL-1βand TNF-αimplicated in psoriasis inhibition by the flavonoid methoxyluteolin[J].Faseb Journal,2015,194(1):67.
[25]Harden J L,Krueger J G,Bowcock A M.The immunogenetics of Psoriasis:A comprehensive review[J].J Autoimmun,2015,64:66-73.
[26]杨丽红,刘靖,涂绍忠.中医心理疗法干预银屑病的应用初探[J].中国医药科学,2015,5(4):29-31.
[27]李金娜,高晓敏,王明旭,等.积极心理治疗对银屑病患者心理状况及行为的影响[J].中华护理杂志,2011,46(7):669-671.
[28]揣瑞梅,徐峰,张俊华.心理疗法联合药物治疗寻常型银屑病疗效观察[J].中国麻风皮肤病杂志,2011,27(1):71-72.
[29]郑益志,陈春凤,贾丽莹,等.中医情志疗法对寻常型银屑病患者HAMD、HAMA水平及外周血单胺类神经递质的影响[J].浙江中医药大学学报,2013,37(5):506-510.
[30]蔡思琪,李沅衡,黎嘉,等.鼠类行为学实验方法研究进展[J].医学综述,2018,24(5):916-920.
[31]李琦军,邢兆国,常军英.神经肽Y在中枢神经系统中的作用[J].河北医科大学学报,2016,37(4):484-486.
[32]Buttari B,Profumo E,Domenici G,et al.Neuropeptide Yinduces potent migration of human immature dendritic cells and promotes a Th2 polarization[J].FASEB J,2014,28(7):3038-3049.
[33]吴岚村,马金路,郝世胜.抑郁障碍患者血浆神经肽Y水平研究[J].临床精神医学杂志,2018,28(3):208.
[34]胡春燕,李英文.神经肽Y(NPY)的生理功能研究进展[J].生物学杂志,2011,28(2):66-68.
[35]曹林,沈丽华.焦虑症患者生活质量评分与血清中神经肽Y表达的相关性[J].中国老年学杂志,2018,38(9):2175-2176.
[2]张建中.银屑病的流行病学与危险因素[J].实用医院临床杂志,2013,10(1):4-6.
[3]Aleem D,Tohid H.Pro-inflammatory Cytokines,Biomarkers,Genetics and the Immune System:A Mechanistic Approach of Depression and Psoriasis[J].Rev Colomb Psiquiatr,2018,47(3):177-186.
[4]Gordon K B,Armstrong A W,Han C,et al.Anxiety and depression in patients with moderate-to-severe psoriasis and comparison of change from baseline after treatment with guselkumab vs.adalimumab:results from the Phase 3 VOYAGE 2study[J].J Eur Acad Dermatol Venereol,2018,99(4):925.
[5]Kurd S K,Troxel A B,Critschristoph P,et al.The risk of depression,anxiety,and suicidality in patients with psoriasis:a population-based cohort study[J].Archives of Dermatology,2010,14(8):891-895.
[6]饶俊昌,龚爱华.银屑病患者的焦虑、抑郁的精神状态及行为特点[J].中国健康心理学杂志,2017(5):677-680.
[7]张强.北方汉族银屑病患者心理健康状况调查[J].世界最新医学信息文摘,2016,16(52):229-230.
[8]陈小玉,贺春香,叶流,等.银屑病患者焦虑抑郁情绪调查[J].西部医学,2015(1):61-62.
[9]郝建侠,吴筱娟,赵梦秋,等.心理护理干预对改善银屑病患者焦虑抑郁状态的影响[J].护理实践与研究,2017(11):251.
[10]许静芳,林贤娜,张璇君,等.心理干预对银屑病患者焦虑抑郁情绪的影响[J].吉林医学,2015,36(4):747-748.
[11]王聪敏,李海涛,余明莲,等.心理护理对银屑病患者心理状态的影响[J].实用皮肤病学杂志,2014,7(2):138-139.
[12]刘艳,路永红,黄晶,等.系统性心理行为干预与药物联合治疗银屑病的研究[J].四川医学,2012,33(10):1736-1738.
[13]刘巧,吴伟伟,王爱民,等.系统性心理行为干预对银屑病患者影响的研究[J].中国中西医结合皮肤性病学杂志,2011,10(1):56-58.
[14]张剑,邓永琼,杨茜,等.杨文信从肝论治寻常型银屑病经验[J].河南中医,2012,32(9):1129-1130.
[15]李咏梅.从肝论治银屑病临床撷英--师从顾氏外科传人马绍尧教授临床经验总结[C]//中华中医药学会学术会议,国家中医药管理局继续教育项目--银屑病中医药防治交流会暨赵炳南学术思想高级研修班资料.北京:中华中医药学会,2011.
[16]徐文俊,毛常亮,冯仁洋,等.凉血活血汤对寻常型银屑病进展期患者外周血Th17相关因子的干预作用[J].中国麻风皮肤病杂志,2018,34(1):45-47.
[17]刘欣,李萍,赵京霞,等.凉血活血胶囊全方及拆方对Jurkat T淋巴细胞增殖、活化及释放细胞因子的影响[J].中国实验方剂学杂志,2012,18(22):198-202.
[18]底婷婷,赵京霞,王燕,等.凉血活血胶囊对咪喹莫特诱导小鼠银屑病样皮损的干预作用[J].中国病理生理杂志,2012,28(4):718-722.
[19]黄继汉,黄晓晖,陈志扬,等.药理试验中动物间和动物与人体间的等效剂量换算[J].中国临床药理学与治疗学,2004,9(9):1069-1072.
[20]van der Fits L,Mourits S,Voerman J S,et al.Imiquimodinduced psoriasis-like skin inflammation in mice is mediated via the IL-23/IL-17 axis[J].J Immunol,2009,182(9):5836-5845.
[21]Parisi R,Symmons D P,Griffiths C E,et al.Global epidemiology of psoriasis:a systematic review of incidence and prevalence[J].J Invest Dermatol,2013,133(2):377-385.
[22]Deng Y,Chang C,Lu Q.The Inflammatory Response in Psoriasis:a Comprehensive Review[J].Clin Rev Allergy Immunol,2016,50(3):377-389.
[23]Nair R P,Duffin K C,Helms C,et al.Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaBpathways[J].Nat Genet,2009,41(2):199-204.
[24]Taracanova A,Theoharides T.Substance P and IL-33Synergistically Stimulate Mast Cells to Release IL-1βand TNF-αimplicated in psoriasis inhibition by the flavonoid methoxyluteolin[J].Faseb Journal,2015,194(1):67.
[25]Harden J L,Krueger J G,Bowcock A M.The immunogenetics of Psoriasis:A comprehensive review[J].J Autoimmun,2015,64:66-73.
[26]杨丽红,刘靖,涂绍忠.中医心理疗法干预银屑病的应用初探[J].中国医药科学,2015,5(4):29-31.
[27]李金娜,高晓敏,王明旭,等.积极心理治疗对银屑病患者心理状况及行为的影响[J].中华护理杂志,2011,46(7):669-671.
[28]揣瑞梅,徐峰,张俊华.心理疗法联合药物治疗寻常型银屑病疗效观察[J].中国麻风皮肤病杂志,2011,27(1):71-72.
[29]郑益志,陈春凤,贾丽莹,等.中医情志疗法对寻常型银屑病患者HAMD、HAMA水平及外周血单胺类神经递质的影响[J].浙江中医药大学学报,2013,37(5):506-510.
[30]蔡思琪,李沅衡,黎嘉,等.鼠类行为学实验方法研究进展[J].医学综述,2018,24(5):916-920.
[31]李琦军,邢兆国,常军英.神经肽Y在中枢神经系统中的作用[J].河北医科大学学报,2016,37(4):484-486.
[32]Buttari B,Profumo E,Domenici G,et al.Neuropeptide Yinduces potent migration of human immature dendritic cells and promotes a Th2 polarization[J].FASEB J,2014,28(7):3038-3049.
[33]吴岚村,马金路,郝世胜.抑郁障碍患者血浆神经肽Y水平研究[J].临床精神医学杂志,2018,28(3):208.
[34]胡春燕,李英文.神经肽Y(NPY)的生理功能研究进展[J].生物学杂志,2011,28(2):66-68.
[35]曹林,沈丽华.焦虑症患者生活质量评分与血清中神经肽Y表达的相关性[J].中国老年学杂志,2018,38(9):2175-2176.