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探讨桃红四物汤在治疗银屑病中的抗炎作用及对Caspase-14、EVPL干预作用机制

Taohong Siwutang Exerts Anti-inflammatory Effect and Regulates Caspase-14 and EVPL Expression in Treatment of Psoriasis
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摘要 目的:探讨桃红四物汤对小鼠银屑病模型炎症因子及胱天蛋白酶(Caspase)-14、外皮蛋白(EVPL)干预作用机制。方法:将48只BALB/c小鼠随机分为空白组、模型组、甲氨蝶呤片组(3.6×10^(-4)g·kg^(-1))、桃红四物汤低、中、高剂量组(7.14、14.28、28.56 g·kg^(-1)),采用小鼠背部涂抹5%咪喹莫特乳膏的方法诱导小鼠银屑病样皮损模型,造模同时给予药物干预。通过拍照进行银屑病面积与严重性指数(PASI)评分;苏木素-伊红(HE)染色观察皮损组织病理改变进行银屑病皮肤病理观察(Baker评分);酶联免疫吸附测定法(ELISA)检测小鼠外周血中白细胞介素(IL)-2、IL-17、IL-22、IL-23炎症因子水平;免疫组化染色检测小鼠皮损组织中Caspase-14、EVPL阳性表达;蛋白免疫印迹法(Western blot)和实时荧光定量聚合酶链式反应(Real-time PCR)检测小鼠皮损组织中IL-2、IL-17、IL-22、IL-23、Caspase-14、EVPL蛋白及基因表达水平。结果:与空白组比较,模型组小鼠皮损PASI评分、Baker评分和外周血中IL-2、IL-17、IL-22、IL-23炎症因子水平明显升高,皮损组织中IL-2、IL-17、IL-22、IL-23 mRNA及蛋白表达水平明显升高,Caspase-14、EVPL mRNA、阳性表达及蛋白表达水平明显降低(P<0.05);与模型组比较,各给药组小鼠皮损PASI评分、Baker评分和外周血中IL-2、IL-17、IL-22、IL-23炎症因子水平明显降低,皮损组织中IL-2、IL-17、IL-22、IL-23 mRNA及蛋白表达水平明显降低,Caspase-14、EVPL mRNA、阳性表达及蛋白表达水平明显升高(P<0.05)。结论:桃红四物汤在治疗银屑病中具有较好的抗炎作用和修复皮肤屏障功能,可以明显降低小鼠银屑病模型外周血、皮损组织中炎症因子水平,促进皮肤屏障修复相关蛋白Caspase-14、EVPL表达。 Objective:To explore the mechanism of Taohong Siwutang in regulating the levels of inflammatory mediators,cysteine-dependent aspartate-specific protease Caspase-14,and recombinant envoplakin(EVPL)in the mouse model of psoriasis.Method:Forty-eight BALB/c mice were randomized into blank,model,methotrexate tablets(3.6×10^(-4)g·kg^(-1)),and low-,medium-,and high-dose Taohong Siwutang groups(7.14,14.28,28.56 g·kg^(-1)).The mouse model of psoriasis-like skin lesion was induced by applying 5%imiquimod cream on the back of mice,and drug intervention was carried out at the same time.The psoriasis area and severity index(PASI)was scored by photographing.Hematoxylin-eosin staining was employed to observe the pathological changes of the skin,which was evaluated based on the Baker score.The levels of interleukin(IL)-2,IL-17,IL-22,and IL-23 in the peripheral blood of mice were measured by the enzyme-linked immunosorbent assay.Immunohistochemical staining was adopted to detect the positive expression of Caspase-14 and EVPL in mouse skin lesions.Western blot and real-time polymerase chain reaction were employed to determine the protein and mRNA levels,respectively,of IL-2,IL-17,IL-22,IL-23,Caspase-14,and EVPL in mouse skin lesions.Result:Compared with the blank group,the model group showed increased PASI score and Baker score,elevated levels of IL-2,IL-17,IL-22,and IL-23 in the peripheral blood,upregulated mRNA and protein levels of IL-2,IL-17,IL-22 and IL-23,and down-regulated mRNA and protein levels and positive expression of Caspase-14 and EVPL in skin lesions(P<0.05).Compared with the model group,drug interventions reduced the PASI score and Baker score,lowered the levels of IL-2,IL-17,IL-22,and IL-23 in the peripheral blood,down-regulated the mRNA and protein levels of IL-2,IL-17,IL-22,and IL-23,and up-regulated the mRNA and protein levels and positive expression of Caspase-14 and EVPL in skin lesions(P<0.05).Conclusion:Taohong Siwutang demonstrates good anti-inflammatory effect and skin barrier repair function in the tr
作者 牛凡琪 李炳男 王思农 李怡霏 周文丽 NIU Fanqi;LI Bingnan;WANG Sinong;LI Yifei;ZHOU Wenli(Gansu University of Chinese Medicine,Lanzhou 730000,China;Zhengzhou Health Vocational College,Zhengzhou 450000,China;Affiliated Hospital of Gansu University of Chinese Medicine,Lanzhou 730000,China)
出处 《中国实验方剂学杂志》 CAS CSCD 北大核心 2024年第20期12-21,共10页 Chinese Journal of Experimental Traditional Medical Formulae
基金 国家重点研发计划“中医药现代化研究”重点专项(2018YFC1705302) 甘肃省高等学校科技成果转化项目(2017D-17)。
关键词 桃红四物汤 小鼠银屑病模型 炎症因子 胱天蛋白酶(Caspase)-14 外皮蛋白(EVPL) Taohong Siwutang mouse model of psoriasis inflammatory mediator Caspase-14 recombinant envoplakin(EVPL)
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