厚朴酚对咪喹莫特诱导的小鼠银屑病样皮损的作用及其机制研究
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摘要
目的探究厚朴酚对咪喹莫特银屑病小鼠模型的作用及可能的机制。方法按照体重将BALB/C雄性小鼠随机分为7组:正常组(涂抹等量凡士林,同时灌胃0. 9%NaCl 0. 2 mL)、模型组(涂抹咪喹莫特60 mg,同时灌胃0. 9%NaCl 0. 2 mL)、阴性对照组(造模的同时,灌胃脂肪乳0. 2 mL)、阳性对照组(造模的同时,灌胃地塞米松磷酸钠注射液5 mg·kg~(-1))和低、中、高3个剂量实验组(造模的同时,灌胃90,30,10 mg·kg~(-1)的厚朴酚脂肪乳制剂0. 2 mL),每组6只。用咪喹莫特诱导小鼠银屑病模型,造模后第6天开始给药,连续7 d。用免疫组化检测小鼠皮肤组织中白细胞介素17(IL-17)、白细胞介素23(IL-23)、Janus激酶2(JAK2)、信号传导子与转录激活子3(STAT3)蛋白的表达水平(均为平均光密度值)。结果模型组与高剂量实验组的IL-17分别为671. 32±225. 63,290. 83±83. 89;这2组的IL-23分别为580. 36±108. 63,273. 41±57. 29;这2组的JAK2分别为509. 16±183. 98,283. 71±83. 47;这2组的STAT3分别为551. 84±126. 47,270. 19±75. 72。高剂量实验组与模型组比较,上述指标的表达量均有不同程度的下降,差异均有统计学意义(均P <0. 05)。结论高剂量厚朴酚对咪喹模特诱导的皮肤银屑病样损害具有改善作用,这种改善作用与IL-17/IL-23炎症通路下调JAK 2和STAT 3的蛋白质水平的表达有关。
Objective To explore the effect of Magnolol on psoriasis mouse model induced by imiquimod and its possible mechanisms.Methods Male BALB/C mice were randomly divided into 7 groups:normal group( apply vaseline and lavage 0. 9% NaCl 0. 2 mL),model group( apply lmiquimod and lavage 0. 9% NaCl 0. 2 mL),negative group( model mice were given apply lmiquimod and fat milk),positive group( model mice were given dexamethasone sodium phosphate injection 5 mg·kg~(-1)) and high dose,middle dose and low dose experimental groups( model mice were given Magnolol 90,30,10 mg·kg~(-1)),6 mouse in each group. Mice model of psoriasis induced by imiquimod was administered on the sixth day after modeling,and lasted for 7 d. The expression level( values of light density) of interleukin-17( IL-17),interleukin-23( IL-23),and Janus kinase 2( JAK2),signal transducer and activator of transcription 3( STAT3) in skin of mice was detected by immunohistochemistry. Results The IL-17 level in model group and high doseexperimental group were 671. 32 ± 225. 63,290. 83 ± 113. 89; the IL-23 level in the 2 group were 580. 36 ± 108. 63,273. 41 ± 57. 29; the JAK2 level in the 2 group were 509. 16 ± 183. 98,283. 71 ± 83. 47; the STAT3 level in the 2 group were 551. 84 ± 126. 47,270. 19 ± 75. 72. Comparison between high dose experimental group and model group,the difference of above factors had significantly( all P < 0. 05). Conclusion The high-dose of Magnolol had a preventive and therapeutic effect on the skin psoriasis-like damage induced by imiquimod. Furthermore,its protective effect is related to the down-regulation of the expression of JAK2 and STAT3 by IL-17/IL-23 pathway.
Objective To explore the effect of Magnolol on psoriasis mouse model induced by imiquimod and its possible mechanisms.Methods Male BALB/C mice were randomly divided into 7 groups:normal group( apply vaseline and lavage 0. 9% NaCl 0. 2 mL),model group( apply lmiquimod and lavage 0. 9% NaCl 0. 2 mL),negative group( model mice were given apply lmiquimod and fat milk),positive group( model mice were given dexamethasone sodium phosphate injection 5 mg·kg~(-1)) and high dose,middle dose and low dose experimental groups( model mice were given Magnolol 90,30,10 mg·kg~(-1)),6 mouse in each group. Mice model of psoriasis induced by imiquimod was administered on the sixth day after modeling,and lasted for 7 d. The expression level( values of light density) of interleukin-17( IL-17),interleukin-23( IL-23),and Janus kinase 2( JAK2),signal transducer and activator of transcription 3( STAT3) in skin of mice was detected by immunohistochemistry. Results The IL-17 level in model group and high doseexperimental group were 671. 32 ± 225. 63,290. 83 ± 113. 89; the IL-23 level in the 2 group were 580. 36 ± 108. 63,273. 41 ± 57. 29; the JAK2 level in the 2 group were 509. 16 ± 183. 98,283. 71 ± 83. 47; the STAT3 level in the 2 group were 551. 84 ± 126. 47,270. 19 ± 75. 72. Comparison between high dose experimental group and model group,the difference of above factors had significantly( all P < 0. 05). Conclusion The high-dose of Magnolol had a preventive and therapeutic effect on the skin psoriasis-like damage induced by imiquimod. Furthermore,its protective effect is related to the down-regulation of the expression of JAK2 and STAT3 by IL-17/IL-23 pathway.
引文
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[4]张勇,唐方.厚朴酚药理作用的最新研究进展[J].中国中药杂志,2012,37(23):3526-3530.
[5]王颖,底婷婷,阮智通,等.凉血解毒汤对银屑病小鼠皮肤组织CCL20/CCR6表达的影响[J].中国病理生理杂志,2015,31(2):331-336.
[6]钟淇滨,祝曙光,陆少君,等.厚朴酚对咪喹莫特诱导小鼠银屑病的干预作用[J].中国药理学通报,2018,34(5):626-631.
[7]VAN D F L,MOURITS S,VOERMAN J S,et al.Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23/IL-17 axis[J].J Immunol,2009,182(9):5836-5845.
[8]BLAUVELT A.T-helper 17 cells in psoriatic plaques and additional genetic links between IL-23 and psoriasis[J].J Invest Dermatol,2008,128(5):1064-1067.
[9]KOMIYAMA Y,NAKAE S,MATSUKI T,et al.IL-17 plays an important role in the development of experimental autoimmune encephalomyelitis[J].J Immunol,2006,177(1):566-573.