北京中医药大学第三附属医院皮肤科,北京 100029
李林仙,女,28岁,博士研究生。研究方向:中医药防治特应性皮炎。
孙占学,E-mail:sunzhanxue@163.com
收稿:2025-08-18,
纸质出版:2025-11-25
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李林仙,范子怡,黄凯歌,等.基于线粒体形态和分裂探讨凉血祛湿止痒方治疗特应性皮炎小鼠的作用机制[J].北京中医药,2025,44(11):1390-1396.
LI Linxian,FAN Ziyi,HUANG Kaige,et al.Mechanisms of Liangxue Qushi Zhiyang Formula in treatment of atopic dermatitis in mice based on mitochondrial morphology and fission[J]. Beijing Journal of Traditional Chinese Medicine,2025,44(11):1390-1396.
李林仙,范子怡,黄凯歌,等.基于线粒体形态和分裂探讨凉血祛湿止痒方治疗特应性皮炎小鼠的作用机制[J].北京中医药,2025,44(11):1390-1396. DOI: 10.16025/j.1674-1307.2025.11.004.
LI Linxian,FAN Ziyi,HUANG Kaige,et al.Mechanisms of Liangxue Qushi Zhiyang Formula in treatment of atopic dermatitis in mice based on mitochondrial morphology and fission[J]. Beijing Journal of Traditional Chinese Medicine,2025,44(11):1390-1396. DOI: 10.16025/j.1674-1307.2025.11.004.
目的
2
基于线粒体形态和分裂探讨凉血祛湿止痒方治疗特应性皮炎小鼠的作用机制。
方法
2
采用随机数字表法将32只小鼠分为正常组、模型组、中药组和阳性药物(对照)组,各8只。除正常组外,其他各组用2,4-二硝基氯苯(DNCB)制备特应性皮炎模型。中药组予凉血祛湿止痒方生药5.2 g/(kg·d),对照组予氯雷他定片13.13 mg/(kg·d),正常组和模型组予等体积生理盐水,每天分2次灌胃,疗程1周。治疗前后采用湿疹面积及严重程度指数(EASI)评分对皮损进行评价,统计小鼠30 min内的抓挠次数,苏木精-伊红(HE)染色观察背部皮肤组织病理学改变,透射电镜观察胸腺细胞线粒体超微结构,蛋白免疫印迹(WB)法检测皮损组织动力相关蛋白1(Drp1)、受线粒体分裂因子(Mff)、裂变蛋白1(Fis1)表达。
结果
2
与正常组比较,模型组小鼠在治疗前后背部皮肤红斑、丘疹/水肿、表皮剥脱、苔藓化以及总分均高(
P
<
0.01),搔抓次数多(
P
<
0.01);组织病理提示表皮增厚,炎症细胞浸润;电镜下观察小鼠胸腺细胞线粒体结构呈水肿、空泡状,嵴断裂、溶解;皮损组织中Drp1、Mff、Fis1蛋白表达高(
P
<
0.01)。治疗后,与模型组比较,中药组小鼠各项皮损评分及总分均低(
P
<
0.01),搔抓次数少(
P
<
0.05),表皮增厚及炎症浸润均改善;小鼠胸腺细胞线粒体结构基本正常,嵴较致密,管腔狭窄细长,结构较清晰;皮损组织中Drp1、Mff和Fis1蛋白表达均低(
P
<
0.01)。治疗后,对照组的有效率为37.5%,中药组为87.5%。
结论
2
凉血祛湿止痒方可改善特应性皮炎小鼠的皮损、瘙痒和组织病理改变,其作用机制可能与抑制Drp1、Mff、Fis1等线粒体分裂相关蛋白表达,调节线粒体形态有关。
Objective
2
To investigate the mechanisms of
Liangxue Qushi Zhiyang Formula
in the treatment of atopic dermatitis in mice based on mitochondrial morphology and fission.
Methods
2
Thirty-two mice were randomly divided into normal group, model group, Chinese medicine group, and positive drug (control) group, with 8 mice in each group. Except for the normal group, atopic dermatitis was induced in all groups using 2,4-dinitrochlorobenzene (DNCB). The Chinese medicine group was administered
Liangxue Qushi Zhiyang Formula
at a crude drug dose of 5.2 g/(kg•d), the control group was administered loratadine tablets at a dose of 13.13 mg/(kg•d), and the normal and model groups were given an equal volume of normal saline. All treatments were administered by gavage twice daily for 1 week. Before and after treatment, skin lesions were evaluated using the Eczema Area and Severity Index (EASI) score, and the number of scratching episodes within 30 min was recorded. Histopathological changes in dorsal skin tissues were observed by hematoxylin-eosin (HE) staining. The ultrastructure of mitochondria in thymic cells was examined by transmission electron microscopy. Protein expression levels of dynamin-relat
ed protein 1 (Drp1), mitochondrial fission factor (Mff), and fission protein 1 (Fis1) in skin lesion tissues were detected by Western blot.
Results
2
Compared with the normal group, mice in the model group showed significantly higher scores for dorsal skin erythema, papules/edema, epidermal exfoliation, lichenification, and total score both before and after treatment(
P
<
0.01), as well as significantly increased scratching episodes(
P
<
0.01). Histopathological examination showed epidermal thickening and inflammatory cell infiltration. Transmission electron microscopy revealed mitochondrial edema and vacuolization, with disrupted and dissolved cristae in thymic cells. The expression levels of Drp1, Mff, and Fis1 proteins in skin lesion tissues were significantly increased(
P
<
0.01). After treatment, compared with the model group, the Chinese medicine group showed significantly lower scores for all skin lesion items and total score(
P
<
0.01), as well as fewer scratching episodes(
P
<
0.05). Epidermal thickening and inflammatory infiltration were improved. Mitochondrial structure in thymic cells was basically normal, with relatively dense cristae, narrow and elongated lumens, and clearer structures. The expression levels of Drp1, Mff, and Fis1 proteins in skin lesion tissues were significantly decreased(
P
<
0.01). After treatment, the effective rate was 37.5% in the control group and 87.5% in the Chinese medicine group.
Conclusion
2
Liangxue Qushi Zhiyang Formula
can improve skin lesions, pruritus, and histopathological changes in mice with atopic dermatitis. Its mechanisms may be related to the inhibition of mitochondrial fission-related proteins such as Drp1, Mff, and Fis1, thereby regulating mitochondrial morphology.
中华医学会皮肤性病学分会免疫学组 , 特应性皮炎协作研究中心 . 中国特应性皮炎诊疗指南(2020版) [J ] . 中华皮肤科杂志 , 2020 , 53 ( 2 ): 81 - 88 .
TSAI TF , RAJAGOPALAN M , CHU CY , et al . Burden of atopic dermatitis in Asia [J ] . J Dermatol , 2019 , 46 ( 10 ): 825 - 834 .
LANGAN SM , IRVINE AD , WEIDINGER S . Atopic dermatitis [J ] . Lancet , 2020 , 396 ( 10247 ): 345 - 360 .
ANDRIEUX P , CHEVILLARD C , CUNHA-NETO E , et al . Mitochondria as a Cellular Hub in Infection and Inflammation [J ] . Int J Mol Sci , 2021 , 22 ( 21 ): 11338 .
DUAN T , DU Y , XING C , et al . Toll-like receptor signaling and its role in cell-mediated immunity [J ] . Front Immunol , 2022 , 13 : 812774 .
IYER D , MISHRA N , AGRAWAL A . Mitochondrial function in allergic disease [J ] . Curr Allergy Asthma Rep , 2017 , 17 ( 5 ): 29 .
BARRERA MJ , AGUILERA S , CASTRO I , et al . Dysfunctional mitochondria as critical players in the inflammation of autoimmune diseases: Potential role in Sjögren's syndrome [J ] . Autoimmun Rev , 2021 , 20 ( 8 ): 102867 .
JI H , LI XK . Oxidative stress in atopic dermatitis [J ] . Oxid Med Cell Longev , 2016 , 2016 : 2721469 .
FADADU RP , ABUABARA K , BALMES JR , et al . Air pollution and atopic dermatitis, from molecular mechanisms to population-level evidence: a review [J ] . Int J Environ Res Public Health , 2023 , 20 ( 3 ): 2526 .
BERTINO L , GUARNERI F , CANNAVÒ SP , et al . Oxidative stress and atopic dermatitis [J ] . Antioxidants (Basel) , 2020 , 9 ( 3 ): 196 .
KIM HJ , LEE SH , JEONG S , et al . Protease-activated receptors 2-antagonist suppresses asthma by inhibiting reactive oxygen species-thymic stromal lymphopoietin inflammation and epithelial tight junction degradation [J ] . Allergy Asthma Immunol Res , 2019 , 11 ( 4 ): 560 - 571 .
李琳 . 动力相关蛋白1调控线粒体分裂影响细胞焦亡在特应性皮炎中的作用 [D ] . 沈阳 : 中国医科大学 , 2021 : 24 - 55 .
WENG Z , ZHOU X , WU H , et al . Dynamin-related protein 1 expression correlates with psoriasis disease severity and regulates keratinocyte function [J ] . Eur J Dermatol , 2020 , 30 ( 4 ): 329 - 337 .
屈欢欢 , 吴思琪 , 李雅宁 , 等 . 从三焦论治特应性皮炎的经验 [J ] . 北京中医药 , 2024 , 43 ( 09 ): 1065 - 1067 .
陈广山 , 段行武 , 李小婷 , 等 . 基于"肝脾相关"探讨特应性皮炎与睡眠障碍的关系 [J ] . 北京中医药 , 2024 , 43 ( 4 ): 421 - 423 .
李瑞欣 , 王萍 , 徐佳 . 基于"水火既济"理论探讨从心肾论治儿童特应性皮炎 [J ] . 北京中医药 , 2024 , 43 ( 4 ): 409 - 412 .
周艺巍 , 徐佳 . 基于"心肾合肤"探讨儿童特应性皮炎的中医证治 [J ] . 北京中医药 , 2024 , 43 ( 9 ): 1061 - 1064 .
孙占学 , 王京军 , 王旭昀 . 凉血祛湿止痒颗粒对特应性皮炎血热湿蕴证患者 IL-17A、IL-23的影响 [J ] . 中华中医药杂志 , 2021 , 36 ( 9 ): 5653 - 5656 .
张慧丽 , 程静 , 李林仙 , 等 . 凉血祛湿止痒汤联合硼酸洗液湿敷治疗特应性皮炎急性发作期血热湿蕴证的临床观察 [J ] . 北京中医药 , 2021 , 40 ( 5 ): 521 - 524 .
李才 , 任立群 . 人类疾病动物模型的复制 [M ] . 北京 : 人民卫生出版社 , 2008 : 35 .
张茜 , 史艳梅 , 李秀敏 , 等 . 基于中西医临床病症特点的特异性皮炎动物模型分析 [J ] . 中国中药杂志 , 2021 , 46 ( 4 ): 762 - 766 .
孙占学 . 凉血祛湿止痒汤对小鼠特应性皮炎模型血清IL-2,IL-4及皮损白三烯B4的影响 [J ] . 中国皮肤性病学杂志 , 2016 , 30 ( 11 ): 1169 - 1171,1210 .
徐叔云 , 卞如濂 , 陈修 . 药理实验方法学 [M ] . 3版 . 北京 : 人民卫生出版社 , 2002 : 202 - 204 .
赵辨 . 中国临床皮肤病学 [M ] . 南京 : 江苏凤凰科学技术出版社 , 2017 : 759 - 765 .
国家食品药品监督管理总局 . 中药新药临床研究一般原则 [EB/OL ] .( 2015-11-03 ) 2025-12-15] . https://www.nmpa.gov.cn/xxgk/ggtg/ypggtg/ypqtggtg/20151103120001444.html https://www.nmpa.gov.cn/xxgk/ggtg/ypggtg/ypqtggtg/20151103120001444.html .
王京军 , 杨薛朝 , 孙占学 . 凉血祛湿止痒汤治疗急性湿疹临床观察 [J ] . 中国中医急症 , 2015 , 24 ( 4 ): 611 - 613 .
余慧敏 , 陈勇 . 孟鲁司特联合氯雷他定治疗儿童特应性皮炎的临床研究 [J ] . 右江医学 , 2017 , 45 ( 3 ): 337 - 339 .
许咏秋 , 王林 , 王婷婷 . 复方紫草油联合氯雷他定治疗轻、中度特应性皮炎的临床观察 [J ] . 皮肤病与性病 , 2020 , 42 ( 2 ): 235 - 237 .
DUBIN C , DEL DUCA E , GUTTMAN-YASSKY E . The IL-4, IL-13 and IL-31 pathways in atopic dermatitis [J ] . Expert Rev Clin Immunol , 2021 , 17 ( 8 ): 835 - 852 .
TILOKANI L , NAGASHIMA S , PAUPE V , et al . Mitochondrial dynamics: overview of molecular mechanisms [J ] . Essays Biochem , 2018 , 62 ( 3 ): 341 - 360 .
ZEMIRLI N , MOREL E , MOLINO D . Mitochondrial Dynamics in Basal and Stressful Conditions [J ] . Int J Mol Sci , 2018 , 19 ( 2 ): 564 .
BUCK MD , O’SULLIVAN D , KLEIN GELTINK RI , et al . Mitochondrial dynamics controls T cell fate through metabolic programming [J ] . Cell , 2016 , 166 ( 1 ): 63 - 76 .
RAMBOLD AS , PEARCE EL . Mitochondrial dynamics at the interface of immune cell metabolism and function [J ] . Trends Immunol , 2018 , 39 ( 1 ): 6 - 18 .
UZHACHENKO R , SHANKER A , DUPONT G . Computational properties of mitochondria in T cell activation and fate [J ] . Open Biology , 2016 , 6 ( 11 ): 160192 .
CHAPMAN NM , CHI H . Metabolic adaptation of lymphocytes in immunity and disease [J ] . Immunity , 2022 , 55 ( 1 ): 14 - 30 .
ALESSANDRO P , PASCALE C , FABRIZIA S . The ever-growing complexity of the mitochondrial fission machinery [J ] . Cell Mol Life Sci , 2018 , 75 ( 3 ): 355 - 374 .
SCHMITT K , GRIMM A , DALLMANN R , et al . Circadian control of Drp1 activity regulates mitochondrial dynamics and bioenergetics [J ] . Cell Metabolism , 2018 , 27 ( 3 ): 657 - 666 .
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