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白芍总苷对雷公藤多苷治疗湿疹的增效减毒作用及机制
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          张明昊 ,王 珍 ,高一盈 ,薛鹏坤 ,马伟洋 ,董文霞 ,马丽亚 ,张大伟 (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)
          中图分类号  R965      文献标志码  A      文章编号  1001-0408(2023)04-0444-07
          DOI  10.6039/j.issn.1001-0408.2023.04.12
          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)。结论  TGP 配伍 TWP 对湿疹模型大鼠具有抗炎增效与肝肾减毒的作用,其机制可能与下调血清促炎因子的表达和抑制
          p38 MAPK通路的激活有关。
          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

          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
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          ZHANG Minghao ,WANG Zhen ,GAO Yiying ,XUE Pengkun ,MA Weiyang ,DONG Wenxia ,MA Liya ,
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          ZHANG Dawei(1.  School  of  Medicine,  Henan  University  of  Chinese  Medicine,  Zhengzhou  450046,  China;
          2.  Clinical  Skills Training  Center,  Henan  University  of  Chinese  Medicine,  Zhengzhou  450046,  China;3.  Dept.
          of  Obstetrics  and  Gynecology,  the  Third  Affiliated  Hospital  of  Henan  University  of  Chinese  Medicine,
          Zhengzhou 450008, China)
          ABSTRACT    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
              Δ  基金项目 河 南 省 大 学 生 创 新 创 业 训 练 计 划 项 目(No.     the  eczema  area  and  severity  index (EASI)  were  scored;  ear
          S202110471025)
                                                              swelling  degree  of  rats  was  measured,  and  the  skin
             *第一作者 高级实验师,硕士。研究方向:基础药理学。E-mail:
          zhangminghao@hactcm.edu.cn                          histomorphology  observation  and  pathological  score  were
              #  通信作者 教 授 。 研 究 方 向 :中 医 内 科 学 。 E-mail:      performed;  protein  expressions  of  p38  mitogen-activated
          13938427612@126.com                                 protein  kinase (p38  MAPK),  phosphorylated  p38  MAPK (p-


          · 444 ·    China Pharmacy  2023 Vol. 34  No. 4                               中国药房  2023年第34卷第4期
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