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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
高级实验师,硕士。研究方向:基础药理学。E-mail:zhangminghao@hactcm.edu.cn
教授。研究方向:中医内科学。E-mail:13938427612@126.com
收稿日期:2022-06-18,
修回日期:2022-12-22,
纸质出版日期:2023-02-28
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张明昊,王珍,高一盈,等.白芍总苷对雷公藤多苷治疗湿疹的增效减毒作用及机制[J].中国药房,2023,34(04):444-449.
ZHANG Minghao,WANG Zhen,GAO Yiying,et al.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[J].ZHONGGUO YAOFANG,2023,34(04):444-449.
张明昊,王珍,高一盈,等.白芍总苷对雷公藤多苷治疗湿疹的增效减毒作用及机制[J].中国药房,2023,34(04):444-449. DOI: 10.6039/j.issn.1001-0408.2023.04.12.
ZHANG Minghao,WANG Zhen,GAO Yiying,et al.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[J].ZHONGGUO YAOFANG,2023,34(04):444-449. DOI: 10.6039/j.issn.1001-0408.2023.04.12.
目的
2
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
2
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
2
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
2
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。
OBJECTIVE
2
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
2
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
2
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 si
gnificantly in model group (
P
<0.05). Compared with model group, EASI scores, ear swelling degree, pathological scores, protein expressions of p38 MAPK and p-p38 MAPK, phosphorylation levels of p38 MAPK and levels of inflammatory indexes were all improved significantly in administration groups (
P
<0.05). The levels of GPT, GOT, SCr and BUN were increased significantly in TWP group, while the serum levels of GOT and SCr in TGP group and serum level of SCr in loratadine group were all decreased significantly (
P
<0.05). The levels of T-SOD in liver and kidney tissue were all decreased significantly in TWP group and compatibility group, while the levels of MDA were increased significantly (
P
<0.05). The compatibility group showed more obvious effect in improving the ear swelling degree, pathological score, p38 MAPK expression and its phosphorylation level and levels of inflammatory indexes, and could reverse the abnormality of liver and kidney indexes caused by TWP (
P
<0.05).
CONCLUSIONS
2
The combination of TGP and TWP has the effects of anti-inflammatory, synergistic and hepatorenal detoxification in eczema model rats. Its mechanism may be associated with down-regulating the expression of serum proinflammatory indexes and inhibiting the activation of p38 MAPK pathway.
汪园园 , 金明华 , 黄颖娟 , 等 . 苓桂术甘汤联合热量限摄对湿疹模型大鼠皮损的影响及其机制分析 [J ] . 中国中西医结合杂志 , 2020 , 40 ( 4 ): 465 - 469 .
阮毅铭 , 梅全喜 , 关健缨 , 等 . 漆大姑水提物外用对慢性皮炎-湿疹模型小鼠的改善作用研究 [J ] . 中国药房 , 2018 , 29 ( 11 ): 1536 - 1541 .
陈佳 , 郭敏 , 周黎旸 , 等 . 野菊花提取物对小鼠湿疹模型Th1/Th2免疫功能的影响 [J ] . 中成药 , 2018 , 40 ( 2 ): 440 - 443 .
何康婧 , 高增平 , 尹丽梅 , 等 . 雷公藤多苷的药理毒理作用研究进展 [J ] . 中国实验方剂学杂志 , 2020 , 26 ( 1 ): 196 - 204 .
任敏霞 , 吴素香 , 詹淑玉 , 等 . 白芍总苷及其所含主要成分芍药苷和芍药内酯苷对四氯化碳致小鼠急性肝损伤的保护作用 [J ] . 中华中医药学刊 , 2020 , 38 ( 5 ): 244 - 247,283 .
张明昊 , 董文霞 , 薛鹏坤 , 等 . 雷公藤多苷对湿疹大鼠皮损的预防作用及机制 [J ] . 山东医药 , 2022 , 62 ( 2 ): 47 - 51 .
庄文欣 , 陈超 , 马一闻 , 等 . 香椿子多酚通过抑制p38MAPK信号通路减轻帕金森病大鼠的神经炎症反应 [J ] . 细胞与分子免疫学杂志 , 2019 , 35 ( 9 ): 794 - 799 .
张荣榕 , 李宁 , 邵帅 , 等 . 基于P38MAPK信号通路探讨加味黄连膏对小鼠湿疹模型的影响 [J ] . 中国医院药学杂志 , 2020 , 40 ( 16 ): 1728 - 1732 .
余伟 , 黄长山 , 丁月超 , 等 . 香叶木素预处理通过抗炎和抗氧化发挥对小鼠肝缺血/再灌注的保护作用 [J ] . 中国药理学通报 , 2022 , 38 ( 7 ): 1017 - 1022 .
杨凡 , 谭正怀 , 石锦萍 , 等 . 蛇黄乳膏止痒功效相关机制 [J ] . 中国实验方剂学杂志 , 2012 , 18 ( 18 ): 210 - 213 .
赵辨 . 湿疹面积及严重度指数评分法 [J ] . 中华皮肤科杂志 , 2004 , 37 ( 1 ): 3 - 4 .
FUKUDA S , MIDORO K , KAMEI T , et al . Inhibition of allergic dermal inflammation by the novel imidazopyridazine derivative TAK-427 in a Guinea pig experimental model of eczema [J ] . J Pharmacol Exp Ther , 2002 , 303 ( 3 ): 1283 - 1290 .
KUNNAS T , NIKKARI S T . Association of the collagen type Ⅳ alpha 1 chain gene rs3783107 GG genotype with hypertension,asthma,and eczema:the Tampere adult population cardiovascular risk study [J ] . Genet Test Mol Biomarkers , 2020 , 24 ( 1 ): 6 - 9 .
MAGRO C , CROWSON A N , FRANKS L , et al . The histologic and molecular correlates of COVID-19 vaccine-induced changes in the skin [J ] . Clin Dermatol , 2021 , 39 ( 6 ): 966 - 984 .
聂丽 . 氯雷他定与白芍总苷联合治疗慢性湿疹的临床疗效 [J ] . 中国误诊学杂志 , 2021 , 16 ( 1 ): 23 - 24 .
MALLABO M R B , CORPUZ M J A T , SALONGA R B , et al . Inhibitory effect of sulfated polysaccharide from Codium edule P.C. silva against 2,4-dinitrofluorobenzene(DNFB)-induced allergic contact dermatitis on female BALB/c mice [J ] . Adv Pharm Bull , 2022 , 12 ( 2 ): 410 - 418 .
MANRESA M C . Animal models of contact dermatitis:2,4-dinitrofluorobenzene-induced contact hypersensitivity [J ] . Methods Mol Biol , 2021 , 2223 : 87 - 100 .
NIE N N , BAI C , SONG S N , et al . Bifidobacterium plays a protective role in TNF-α-induced inflammatory response in Caco-2 cell through NF-κB and p38MAPK pathways [J ] . Mol Cell Biochem , 2020 , 464 ( 1/2 ): 83 - 91 .
LIU D L , WANG K , SU D Y , et al . TMEM16A regulates pulmonary arterial smooth muscle cells proliferation via p38MAPK/ERK pathway in high pulmonary blood flow-induced pulmonary arterial hypertension [J ] . J Vasc Res , 2020 , 58 ( 1 ): 27 - 37 .
ARYANI H P , SANTOSO B , PURWANTO B , et al . The effect of low-calorie high protein diet on insulin,TNF-α and P38MAPK levels in insulin-resistant PCOS mice models [J ] . Syst Rev Pharm , 2020 , 11 : 597 - 605 .
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