白芍总苷对雷公藤多苷治疗湿疹的增效减毒作用及机制  

Study on the effects and mechanism of total glucosides of paeony on enhancing efficacy and reducing toxicity of Tripterygium wilfordii polyglycoside in the treatment of eczema

作　　者：张明昊[1] 王珍[1] 高一盈 薛鹏坤 马伟洋 董文霞 马丽亚[2] 张大伟[3] ZHANG Minghao;WANG Zhen;GAO Yiying;XUE Pengkun;MA Weiyang;DONG Wenxia;MA Liya;ZHANG Dawei(School of Medicine,Henan University of Chinese Medicine,Zhengzhou 450046,China;Clinical Skills Training Center,Henan University of Chinese Medicine,Zhengzhou 450046,China;Dept.of Obstetrics and Gynecology,the Third Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450008,China)

机构地区：[1]河南中医药大学医学院,郑州450046 [2]河南中医药大学临床技能实训中心,郑州450046 [3]河南中医药大学第三附属医院妇产科,郑州450008

出　　处：《中国药房》2023年第4期444-449,456,共7页China Pharmacy

基　　金：河南省大学生创新创业训练计划项目(No.S202110471025)。

摘　　要：目的探讨白芍总苷(TGP)对雷公藤多苷(TWP)治疗湿疹的增效减毒作用及机制。方法取50只雄性SD大鼠,以2,4-二硝基氟苯-丙酮橄榄油溶液(体积比4∶1)腹部致敏+背部、耳部激发的方式构建湿疹大鼠模型。将造模后的大鼠随机分为模型组、氯雷他定组(0.9 mg/kg)、TWP组(9.45 mg/kg)、TGP组(162 mg/kg)、配伍组(TWP 9.45 mg/kg+TGP 162 mg/kg),每组10只;另取10只大鼠,作为正常组。各药物组大鼠于首次致敏3 d后灌胃相应药液,正常组和模型组大鼠灌胃等体积0.1%羧甲基纤维素钠溶液,每天1次,连续21 d。末次给药24 h后,观察各组大鼠的一般情况,并进行湿疹面积及严重度指数(EASI)评分,检测大鼠的耳肿胀度并进行皮肤组织形态学观察和病理评分,检测大鼠皮肤组织中p38丝裂原激活的蛋白激酶(p38 MAPK)、磷酸化p38 MAPK(p-p38 MAPK)蛋白的表达水平及p38 MAPK蛋白的磷酸化水平,检测大鼠炎症(白细胞介素4、γ干扰素)、肝肾功能[谷丙转氨酶(GPT)、谷草转氨酶(GOT)、血肌酐(SCr)、尿素氮(BUN)]、氧化应激指标[总超氧化物歧化酶(T-SOD)、丙二醛(MDA)]水平。结果与正常组比较,模型组大鼠背部皮肤的EASI评分,耳肿胀度,病理评分,p38 MAPK、p-p38 MAPK蛋白的表达水平和p38 MAPK蛋白的磷酸化水平,炎症指标水平,BUN水平均显著升高(P<0.05)。与模型组比较,各药物组EASI评分,耳肿胀度,病理评分,p38 MAPK、p-p38 MAPK蛋白的表达水平和p38 MAPK蛋白的磷酸化水平,炎症指标水平均显著改善(P<0.05);TWP组大鼠GPT、GOT、SCr、BUN水平均显著升高,TGP组大鼠血清中GOT、SCr水平和氯雷他定组大鼠血清中SCr水平均显著降低(P<0.05);TWP组和配伍组大鼠肝、肾组织T-SOD水平均显著降低,MDA水平均显著升高(P<0.05);配伍组在大鼠耳肿胀度、病理评分、p38 MAPK蛋白表达及其磷酸化水平、炎症指标水平方面的改善效果更明显,并可逆转TWP造成的肝肾指标异常(P<0.05)。结OBJECTIVE To investigate the effects of total glucosides of paeony(TGP)on enhancing efficacy and reducing toxicity of Tripterygium wilfordii polyglycoside(TWP)in the treatment of eczema.METHODS Totally 50 SD male rats were collected to establish eczema model by sensitizing with 2,4-dinitrofluorobenzene-acetone olive oil solution(volume ratio was 4∶1)on the abdominal area and provoking on the back and ear.Model rats were randomly divided into model group,loratadine group(0.9 mg/kg),TWP group(9.45 mg/kg),TGP group(162 mg/kg)and compatibility group(TWP 9.45 mg/kg+TGP 162 mg/kg),with 10 rats in each group.Other 10 rats were collected to set as normal group.Three days after the first sensitization,administration groups were given relevant medicine intragastrically,and normal group and model group were given constant volume of 0.1%CMC-Na solution intragastrically,once a day,for consecutive 21 d.Twenty-four hours later after the final administration,the general condition of rats in each group was observed,and the eczema area and severity index(EASI)were scored;ear swelling degree of rats was measured,and the skin histomorphology observation and pathological score were performed;protein expressions of p38 mitogen-activated protein kinase(p38 MAPK),phosphorylated p38 MAPK(p p38 MAPK)and phosphorylation level of p38 MAPK in rat skin tissue were detected;the levels of inflammatory indexes(interleukin-4,interferon-γ),liver and kidney function indexes[glutamic-pyruvic transaminase(GPT),glutamic-oxaloacetic transaminase(GOT),serum creatinine(SCr)and blood urea nitrogen(BUN)]and oxidant stress indexes[total superoxide dismutase(T-SOD)and malondialdehyde(MDA)]were measured.RESULTS Compared with normal group,EASI score,ear swelling degree,pathological score,protein expressions of p38 MAPK and p-p38 MAPK,phosphorylation level of p38 MAPK,the levels of inflammatory indexes and BUN were all increased significantly in model group(P<0.05).Compared with model group,EASI scores,ear swelling degree,pathological scores,protein expressi

关 键 词：白芍总苷 雷公藤多苷 湿疹 增效减毒 p38丝裂原激活的蛋白激酶通路 大鼠 

分 类 号：R965[医药卫生—药理学]