基于p38/NF-κB信号通路探讨海桐皮治疗特应性皮炎机制  

Mechanism of Treating Atopic Dermatitis with Haitongpi(Erythrinae Cortex) Based on p38/NF-κB Signaling Pathway

作　　者：陈曙光 王加锋[1] 周祥禄 陈乐乐 滕佳林[1] CHEN Shuguang;WANG Jiafeng;ZHOU Xianglu;CHEN Lele;TENG Jialin(Shandong University of Traditional Chinese Medicine,Jinan 250355,China)

机构地区：[1]山东中医药大学,山东济南250355

出　　处：《山东中医药大学学报》2023年第2期194-201,共8页Journal of Shandong University of Traditional Chinese Medicine

基　　金：齐鲁医派中医学术流派传承项目(编号:2021-001);山东省研究生教育优质课程和专业学位研究生教学案例库项目(编号:SDYAL20053);山东省研究生教育质量提升计划项目(编号:SDY KC21047)。

摘　　要：目的:研究海桐皮水煎液对特应性皮炎模型小鼠的抗炎作用,并从丝裂原蛋白激酶(p38)/核因子κB(NF-κB)信号通路研究其作用机制。方法:将60只BALB/c雄性小鼠随机分为空白组、模型组、对照组及海桐皮低、中、高浓度组,每组10只。后五组以7%的2,4-二硝基氯苯(DNCB)丙酮溶液100μL涂于小鼠腹部进行致敏诱导。5 d后在小鼠右耳内侧外涂1%的DNCB丙酮溶液10μL激发,每隔3 d激发1次,共激发5次。第一次激发后12 h海桐皮各组开始外洗给药,每次给药5 mL,每日2次,连续给药15 d。对照组予等体积0.025%地塞米松磷酸钠注射液,空白组和模型组予等体积纯净水。检测小鼠耳厚度差、皮损评分及耳肿胀度。治疗结束后,取血清和右耳组织,观察耳组织病理学变化,检测血清免疫球蛋白E(IgE)、白细胞介素-4(IL-4)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)水平,检测NF-κB、p38、磷酸化丝裂原蛋白激酶(p-p38)蛋白表达情况。结果:与模型组比较,各治疗组小鼠耳厚度差、皮损评分及耳肿胀度均降低(P<0.01或P<0.05)。与模型组比较,海桐皮各组小鼠皮肤角化过度、水肿和炎症细胞浸润程度改善;海桐皮中浓度组和高浓度组血清IgE水平降低(P<0.05),低浓度组和高浓度组血清IL-4水平降低(P<0.05),中浓度组和高浓度组血清IL-6水平降低(P<0.01),低浓度组、中浓度组和高浓度组血清TNF-α水平均显著降低(P<0.01)。与空白组比较,模型组NF-κB阳性表达升高(P<0.01);与模型组比较,海桐皮中浓度组和高浓度组NF-κB阳性表达降低(P<0.05或P<0.01)。与空白组比较,模型组p38蛋白表达降低(P<0.01)、p-p38蛋白表达升高(P<0.05);与模型组比较,海桐皮低浓度组p38表达升高(P<0.01),海桐皮各组p-p38蛋白表达均降低(P<0.05或P<0.01)。结论:海桐皮可明显改善特应性皮炎模型小鼠耳病变程度,减少血清IgE、IL-4、IL-6、TNF-α分泌,其机制可能与降低p38蛋白�Objective:To study the anti-inflammatory effect of decoction of Haitongpi(Erythrinae Cortex)on atopic dermatitis model mice,and to study the possible mechanism based on mitogen kinase(p38)/nuclear factor κB(NF-κB) signaling pathway. Methods:Total 60 BALB/c male mice were randomly divided into blank group,model group,control group,and low,medium,high concentration groups of Haitongpi,10 mice in each group. The last five groups of mice were sensitized with 7% 2,4-dinitrochlorobenzene(DNCB) acetone solution 100 μL on the abdomen. Five days later,the mice were stimulated by 1% DNCB acetone solution10 μL on the inside of the right ear,once every 3 days,for a total of 5 times. Twelve hours after the first excitation,external wash administration was started in each group of Haitongpi,and 5 mL was administered twice a day for 15 days. The control group was given equal volume of 0.025% dexamethasone sodium phosphate injection,and the blank group and model group were given equal volume of purified water. The ear thickness difference,skin lesion score and ear swelling degree of mice were measured. After treatment,serum and right ear tissue were taken. The histopathological changes of the ears were observed,the serum concentrations of immunoglobulin E(IgE),interleukin-4(IL-4),interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) were detected,and the protein expressions of NF-κB,p38 and phosphorylated mitogen kinase(p-p38)were detected. Results:Compared with model group,the ear thickness difference,skin lesion score and ear swelling degree of mice in each treatment group were decreased(P< 0.01 or P< 0.05). Compared with model group,the degree of skin hyperkeratosis,edema and inflammatory cell infiltration of mice in each group of Haitongpi was improved;IgE levels in medium and high concentration groups of Haitongpi were decreased(P< 0.05),serum IL-4 levels in low and high concentration groups of Haitongpi were decreased(P< 0.05),and serum IL-6 levels in medium and high concentration groups of Haitongpi were decreased

关 键 词：海桐皮 特应性皮炎 丝裂原蛋白激酶 磷酸化丝裂原蛋白激酶 核因子ΚB 炎症抵抗 小鼠 

分 类 号：R285.5[医药卫生—中药学]