低聚原花青素对DNCB诱导的小鼠皮肤损伤的保护机制  

The Mechanism of Protective Effect of Oligomeric Procyanidins on DNCB-Induced Skin Lesions in Mice

作　　者：徐捷 冒晓香 朱晓玲[1] XU Jie;MAO Xiaoxiang;ZHU Xiaoling(Department of Dermatology,Rugao Hospital of Traditional Chinese Medicine,Rugao 226500,China)

机构地区：[1]如皋市中医院皮肤科,江苏如皋226500

出　　处：《中国皮肤性病学杂志》2022年第5期530-536,共7页The Chinese Journal of Dermatovenereology

摘　　要：目的 观察低聚原花青素对2,4二硝基氯苯(dinitrochlorobenzene, DNCB)诱导的小鼠皮肤损伤的氧化应激、炎症调控作用并探讨其机制。方法 使用DNCB建立小鼠皮损模型。低聚原花青素[50、100、200 mg/(kg·d)]灌胃处理皮损小鼠,观察记录皮损情况。ELISA法检测血清中活性氧(ROS)、丙二醛(MDA)、谷胱甘肽(GSH)、IgE、IL-4、IFN-γ、TNF-α的含量。Western blot检测组织中核因子2相关因子2(Nrf2)/抗氧化反应元件(ARE)信号通路关键基因Nrf2、血红素氧化酶-1(HO-1)、磷酸酰胺腺嘌呤二核苷酸醌氧化还原酶-1(NQO-1)及Toll样受体4(TLR4)/髓样分化因子88(MyD88)/核因子κB(NF-κB)信号通路关键基因TLR4、MyD88、NF-κB P65的蛋白水平。结果 与空白组相比,模型组小鼠皮损评分显著升高(4.58±0.59 vs.1.25±0.18,P<0.05),血清ROS荧光强度、MDA、GSH含量显著升高(7.44±0.55 vs.28.66±3.42,6.61±0.62 vs.17.85±3.38,110.38±7.47 vs.66.60±4.78;P<0.05),Nrf2、HO-1、NQO-1蛋白水平显著升高(0.45±0.07 vs.0.75±0.03,0.25±0.02 vs.0.51±0.06,0.28±0.02 vs.0.57±0.01;P<0.05),血清IgE、IL-4、IFN-γ、TNF-ɑ的含量也显著升高(1.28±0.16 vs.2.59±0.32,11.24±3.38 vs.27.49±3.72,29.01±1.74 vs.47.74±3.38,15.98±2.51 vs.32.51±3.89;P<0.05),TLR4、MyD88和NF-κB P65的蛋白水平也显著升高(0.23±0.03 vs.0.60±0.04,0.33±0.03 vs.0.74±0.04,0.36±0.02 vs.0.86±0.04;P<0.05);低聚原花青素(低剂量、中剂量、高剂量)显著负向调控上述指标的变化。结论 低聚原花青素对DNCB诱导的小鼠皮损具有抗氧化、抗炎功效,其机制与抑制Nrf2/ARE信号通路和TLR4/MyD88/NF-κB信号通路活性有关。Objective To observe the effects of oligomeric procyanidins on oxidative stress and inflammation in mice skin Lesions induced by dinitrochlorobenzene(DNCB) and explore its mechanism.Methods The skin lesion model of mice was established by DNCB.Mice with skin lesions were treated with oligomeric procyanidins [50,100,200 mg/(kg·d),gavage],and the skin lesions were observed and recorded.ELISA was used to detect the content of the fluorescence intensity of reactive oxygen species(ROS),malondialdehyde(MDA),glutathione(GSH),immunoglobulin E(IgE),IL-4,IFN-γ,TNF-α.The key gene products of Nrf2/ARE signaling pathway, nuclear factor-2-related factor 2(Nrf2),heme oxidase-1(HO-1),NADPH quineoxidase-1(NQO-1) and key genes of TLR4/MyD88/NFκB signaling pathway toll-like receptor 4(TLR4),myeloid differentiation factor 88(MyD88),nuclear factor κ B(Nuclear factor κB,NF-κB) P65 were detected by WB.Results Compared with the blank group, the skin lesion score significantly increased in the model group(4.58±0.59 vs.1.25±0.18,P <0.05).The fluorescence intensity of ROS,MDA and GSH in serum were significantly increased(7.44±0.55 vs.28.66±3.42,6.61±0.62 vs.17.85±3.38,110.38±7.47 vs.66.60±4.78;respectively, P<0.05),and the protein levels of Nrf2,HO-1 and NQO-1 significantly augmented(0.45±0.07 vs.0.75±0.03,0.25±0.02 vs.0.51±0.06,0.28±0.02 vs.0.57±0.01;respectively, P<0.05).Serum IgE,IL-4,IFN-γ,TNF-ɑ were also significantly increased(1.28±0.16 vs.2.59±0.32,11.24±3.38 vs.27.49±3.72,29.01±1.74 vs.47.74±3.38,15.98±2.51 vs.32.51±3.89;respectively, P<0.05).The protein level of TLR4,MyD88 and NF-κB P65 were also significantly augmented(0.23± 0.03 vs.0.60±0.04,0.33±0.03 vs.0.74±0.04,0.36±0.02 vs.0.86±0.04;respectively, P<0.05).Oligomeric proanthocyanidins(low dose, medium dose and high dose) significantly negatively regulated the changes in these indexes.Conclusion Oligomeric procyanidins have antioxidant and anti-inflammatory effects on DNCB-induced skin lesions in mice.The mechanism may be related to the inh

关 键 词：低聚原花青素 小鼠皮肤损伤模型 Nrf2/ARE信号通路 TLR4/MyD88/NF-κB信号通路 

分 类 号：R285.5[医药卫生—中药学]