纳米气泡氢水处理对咪喹莫特诱导银屑病小鼠模型的影响

doi:10.19586/j.2095-2341.2024.0008

生物技术进展 ›› 2024, Vol. 14 ›› Issue (4): 676-684.DOI: 10.19586/j.2095-2341.2024.0008

纳米气泡氢水处理对咪喹莫特诱导银屑病小鼠模型的影响

杨建鸿¹(), 刘伯言², 陈军¹, 裘之慧¹, 李宝强¹, 秦树存², 牛艳东¹, 何磊¹()

^1.承德医学院附属医院，河北省泛血管疾病重点实验室，河北承德 067000
^2.山东第一医科大学第二附属医院泰山氢生物医学研究院，山东泰安 271000

收稿日期:2024-01-15 接受日期:2024-04-18 出版日期:2024-07-25 发布日期:2024-08-07
通讯作者: 何磊
作者简介:杨建鸿 E-mail: 819587855@qq.com；
基金资助:
承德市科技计划自筹经费项目(202204A069);河北省财政厅、卫健委政府资助临床医学优秀人才培养项目(ZF2023253);河北省自然科学基金项目(H2019406153);河北省医学科学研究课题计划(20220421)

Effects of Pre-treatment of Nanobubble Hydrogen Water on the Mouse Psoriasis Induction by Imiquimod

Jianhong YANG¹(), Boyan LIU², Jun CHEN¹, Zhihui QIU¹, Baoqiang LI¹, Shucun QIN², Yandong NIU¹, Lei HE¹()

^1.Hebei Key Laboratory Panvascular Diseases，the Affiliated Hospital of Chengde Medical College，Hebei Chengde 067000，China
^2.Taishan Institute of Hydrogen Biomedicine，the Second Affiliated Hospital of Shandong First Medical University，Shandong Taian 271000，China

Received:2024-01-15 Accepted:2024-04-18 Online:2024-07-25 Published:2024-08-07
Contact: Lei HE

摘要/Abstract

摘要：

为了探讨纳米气泡氢水（nano-bubble hydrogen water, NBHW）处理对咪喹莫特(imiquimod, IMQ)诱导的小鼠银屑病的发生和发展的影响以及其作用机制，使用8周龄的雄性BALB/C小鼠，将其随机分为5组，空白组（control，CON）、生理盐水组(normal saline，NS）、NBHW组、卡泊三醇组（clobetasol propionate，CLO）以及联合组（CLO+NBHW）。处理后在小鼠维持原处理同时开始造模，背部去毛皮肤处以及耳朵处涂5% IMQ乳膏。记录小鼠皮损变化，用（psoriasis area and severity index，PASI）银屑病皮损评分评估小鼠的皮损表现。同时采用苏木精-伊红（hematoxylin-eosin，HE）染色法对皮肤组织切片进行染色,并对棘层肥厚程度进行评估，并统计分析各组小鼠脾脏指数情况。此外,利用丙二醛(malondialdehyde，MDA)试剂盒测定血清中的氧化指标，ELISA法检测炎症因子在血清及小鼠背部皮损中的表达水平。评估NBHW对这些炎性细胞因子基因表达的影响。结果发现，各组银屑病小鼠造模成功, NBHW组炎症情况和组织病理学变化较NS组和CON组轻微。NBHW处理可以明显减轻咪喹莫特诱发模型小鼠炎症情况和组织病理变化的严重程度。相对于CON组,NBHW组等组织中炎症因子下调；MDA水平低于CON组。结果表明，NBHW对于咪喹莫特诱导的银屑病小鼠模型表现出显著的防治效果，不仅在皮肤病变的改善上有明显作用，还能够降低炎症因子的产生及氧化指标的表达。

关键词: 银屑病, 纳米气泡氢水, 炎症, 氧化应激

Abstract:

The objective of this study was to explore the impact of nano-bubble hydrogen water （NBHW） pretreatment on the initiation and progression of imiquimod （IMQ）-induced psoriasis in mice， as well as the underlying mechanisms. Eight-week-old male BALB/c mice were randomly assigned to five groups： control （CON）， normal saline （NS）， NBHW， calcipotriol （CLO）， and a combination of CLO and NBHW （CLO+NBHW）. After pretreatment， the psoriasis model was established by administering 5% IMQ cream on the shaved back skin and ears， while maintaining the respective treatments. The evolution of skin lesions was documented， and the severity was assessed using the psoriasis area and severity index （PASI）. Hematoxylin-eosin （HE） staining was employed to examine skin tissue sections， evaluating the degree of acanthosis. The spleen index of each group was statistically analyzed， and serum oxidation levels were determined using a malondialdehyde （MDA） kit. Additionally， ELISA was utilized to detect the expression levels of inflammatory factors in serum and skin lesions. The results demonstrated successful induction of psoriasis in all groups. Notably， the NBHW group exhibited less severe inflammation and histopathological alterations compared to the NS and CON groups. Pretreatment with NBHW significantly mitigated the severity of inflammation and histopathological changes in the IMQ-induced mouse model. Additionally， the expression of inflammatory factors in tissues， such as the NBHW group， was downregulated， and the MDA level was lower than in the CON group. These findings indicated that NBHW exhibit a significant protective effect against IMQ-induced psoriasis in mice， not only improving skin lesions but also reducing the production of inflammatory factors and the expression of oxidative markers.

Key words: psoriasis, nanobubble hydrogen water, inflammation, oxidative stress

中图分类号:

R751

杨建鸿, 刘伯言, 陈军, 裘之慧, 李宝强, 秦树存, 牛艳东, 何磊. 纳米气泡氢水处理对咪喹莫特诱导银屑病小鼠模型的影响[J]. 生物技术进展, 2024, 14(4): 676-684.

Jianhong YANG, Boyan LIU, Jun CHEN, Zhihui QIU, Baoqiang LI, Shucun QIN, Yandong NIU, Lei HE. Effects of Pre-treatment of Nanobubble Hydrogen Water on the Mouse Psoriasis Induction by Imiquimod[J]. Current Biotechnology, 2024, 14(4): 676-684.

图/表 7

图1 第8天各组小鼠背部及耳部皮肤的形态学变化及组织病理学影响A:小鼠第8天皮损程度；B：小鼠第8天背部皮肤组织学形态；C：小鼠第8天耳部皮肤组织学形态。

Fig. 1 Morphological changes and histopathological effects on the skin of mice in each group on Day 8

图2 PASI评分变化及造模第8天PASI评分A: PASI评分变化；B：造模第8天PASI评分。**表示数据在P<0.01水平上有统计学差异，ns表示无统计学差异。

Fig. 2 Change in PASI score of each group and the total score of each group on Day 8

图3 小鼠银屑病模型中棘层增厚及皮肤炎性细胞浸润的分析A:各组小鼠炎症细胞浸润数量；B：各组小鼠棘层增厚程度。***表示数据在P<0.001水平上有统计学差异，ns表示无统计学差异。

Fig. 3 Analysis of epidermal hyperplasia and inflammatory skin infiltration in a mouse psoriasis model

图4 各组小鼠脾脏指数及脾脏大小A:各组小鼠脾脏大小；B：各组小鼠脾脏指数。***表示数据在P<0.001水平上有统计学差异，ns表示无统计学差异。

Fig. 4 Spleen index and spleen size in each group

图5 各组血清MDA水平注：***表示数据在P<0.001水平上有统计学差异，ns表示无统计学差异。

Fig. 5 Serum MDA levels in each group

图6 各组小鼠背部皮肤组织中炎症因子的表达情况A:各组小鼠背部皮肤组织IL-17水平；B:各组小鼠背部皮肤组织TNF-α水平；C:各组小鼠背部皮肤组织IFN-γ水平。*和***分别表示数据在P<0.05和P<0.001水平上有统计学差异，ns表示无统计学差异。

Fig. 6 The pression of inflammatory factors in dorsal skin tissue of each group

图7 各组血清中炎症因子的表达情况A:各组小鼠血清IL-17水平；B:各组小鼠血清TNF-α水平；C:各组小鼠血清IFN-γ水平。*表示数据在P<0.05水平上有统计学差异，ns表示无统计学差异。

Fig. 7 The pression of inflammatory factors in serum of each group

参考文献 38

1	ARMSTRONG A W, HARSKAMP C T, ARMSTRONG E J. The association be tween psoriasis and obesity:a systematic review and meta-analysis of observational studies[J/OL]. Nutr. Diabetes,2012,3(2):e54[2024-05-15]. .
2	范雪莉.银屑病与T细胞和自身免疫[J].国外医学(皮肤性病学分册),1999(2):70-73.
3	STEINHUBL S R. Why have antioxidants failed in clinical trials?[J]. Am. J. Cardiol., 2008, 101(10a): 14D-19D.
4	张译丹,王和平.细胞因子在银屑病中的作用及中医药干预[J].生命的化学,2023,43(12):1886-1895.
5	WATANABE S, FUJITA M, ISHIHARA M, et al.. Protective effect of inhalation of hydrogen gas on radiation-induced dermatitis and skin injury in rats[J]. J. Radiat Res., 2014, 55(6): 1107-1113.
6	MEI K, ZHAO S, QIAN L, et al.. Hydrogen protects rats from dermatitis caused by local radiation[J]. J. Dermatol. Treat., 2014, 25(2): 182-188.
7	GUO Z, ZHOU B, LI W, et al.. Hydrogen-rich saline protects against ultraviolet B radiation injury in rats[J]. J. Biomed. Res., 2012, 26(5): 365-371.
8	SHIN M H, PARK R, NOJIMA H, et al.. Atomic hydrogen surrounded by water molecules, H(H₂O)m, modulates basal and UV-induced gene expressions in human skin in vivo [J/OL]. PLoS One, 2013, 8(4): e61696[2024-05-15]. .
9	ZHU Q, WU Y, LI Y, et al.. Positive effects of hydrogen-water bathing in patients of psoriasis and parapsoriasis en plaques[J/OL]. Sci. Rep., 2018, 8: 8051[2024-05-15]. .
10	李婷竹,郭冀峰,王嘉琳,等.微纳米气泡及其在环境工程领域的应用[J].净水技术,2021,40(2):88-92+110.
	LI T Z, GUO J F, WANG J L, et al.. Micro and nano bubbles and the applications in environmental engineering[J]. Water Purif. Technol., 2021, 40(2): 88-92+110.
11	KATO S, MATSUOKA D, MIWA N. Antioxidant activities of nano-bubble hydrogen-dissolved water assessed by ESR and 2, 2'-bipyridyl methods[J]. Mater. Sci. Eng. C Mater Biol. Appl., 2015, 53: 7-10.
12	陆家睛,史玉玲.中国银屑病生物治疗专家共识(2019版)解读[J].同济大学学报(医学版),2021,42(4):441-444.
	LU J J, SHI Y L. Interpretation of the Chinese expert consensus on the biological treatment for psoriasis(2019 edition)[J]. J. Tongji Univ. Med. Sci., 2021, 42(4): 441-444.
13	朱愿超,孙雪林,胡欣.银屑病治疗靶向药物的研究进展[J].中国药房,2019,30(4):542-547.
	ZHU Y C, SUN X L, HU X. Research progress of targeted drugs for psoriasis treatment[J]. China Pharm., 2019, 30(4):542-547.
14	汤归绍. 有氧运动对银屑病的改善作用及其机制初探[D].长沙:中南大学,2022.
15	SI Y, TIAN H, DONG B, et al.. Effects of hydrogen as adjuvant treatment for unstable angina[J]. Exp. Biol. Med. Maywood., 2021, 246(18): 1981-1989.
16	MEDOVIC M V, JAKOVLJEVIC V L, ZIVKOVIC V I, et al.. Psoriasis between autoimmunity and oxidative stress: changes induced by different therapeutic approaches[J/OL]. Oxid. Med. Cell Longev., 2022, 2022: 2249834[2024-05-15]. .
17	BAI G, LI H, GE Y, et al.. Influence of hydrogen-rich saline on hepatocyte autophagy during laparoscopic liver ischaemia-reperfusion combined resection injury in miniature pigs[J]. J. Vet. Res., 2018, 62(3): 395-403.
18	QIAN L, SHEN J, CHUAI Y, et al.. Hydrogen as a new class of radioprotective agent[J]. Int. J. Biol. Sci., 2013, 9(9): 887-894.
19	SHAO A, WU H, HONG Y, et al.. Hydrogen-rich saline attenuated subarachnoid hemorrhage-induced early brain injury in rats by suppressing inflammatory response: possible involvement of NF-κB pathway and NLRP3 inflammasome[J]. Mol. Neurobiol., 2016, 53(5): 3462-3476.
20	ISHIBASHI T, ICHIKAWA M, SATO B, et al.. Improvement of psoriasis-associated arthritis and skin lesions by treatment with molecular hydrogen: a report of three cases[J]. Mol. Med. Rep., 2015, 12(2): 2757-2764.
21	ZHOU P, LIN B, WANG P, et al.. The healing effect of hydrogen-rich water on acute radiation-induced skin injury in rats[J]. J. Radiat. Res., 2019, 60(1): 17-22.
22	LI Q, KATO S, MATSUOKA D, et al.. Hydrogen water intake via tube-feeding for patients with pressure ulcer and its reconstructive effects on normal human skin cells in vitro [J/OL]. Med. Gas Res., 2013, 3(1): 20[2024-05-15]. .
23	ASADA R, SAITOH Y, MIWA N. Effects of hydrogen-rich water bath on visceral fat and skin blotch, with boiling-resistant hydrogen bubbles[J]. Med. Gas Res., 2019, 9(2): 68-73.
24	郑蒙娜,涂秋芬,吕磊,等.富氢水对2型糖尿病大鼠皮肤创面的促愈作用[J].华西药学杂志,2021,36(4):383-387.
	ZHENG M N, TU Q F, LYU L, et al.. Healing-promoting effects of hydrogen-rich water on skin wounds of type 2 diabetic rats[J]. West China J. Pharm. Sci., 2021, 36(4): 383-387.
25	QI D D, DING M Y, WANG T, et al.. The therapeutic effects of oral intake of hydrogen rich water on cutaneous wound healing in dogs[J/OL]. Vet. Sci., 2021, 8(11): 264[2024-05-14]. .
26	FAN W, ZHANG Y, LIU S, et al.. Alleviation of copper toxicity in Daphnia magna by hydrogen nanobubble water[J/OL]. J. Hazard. Mater., 2020, 389: 122155[2024-05-14]. .
27	ZHANG Y, FAN W, LI X, et al.. Enhanced removal of free radicals by aqueous hydrogen nanobubbles and their role in oxidative stress[J]. Environ. Sci. Technol., 2022, 56(21): 15096-15107.
28	RIOL-BLANCO L, ORDOVAS-MONTANES J, PERRO M, et al.. Nociceptive sensory neurons drive interleukin-23-mediated psoriasiform skin inflammation[J]. Nature, 2014, 510: 157-161.
29	WAGNER E F, SCHONTHALER H B, GUINEA-VINIEGRA J, et al.. Psoriasis: what we have learned from mouse models[J]. Nat. Rev. Rheumatol., 2010, 6: 704-714.
30	FRIEDRICH M, KRAMMIG S, HENZE M, et al.. Flow cyto- metric characterization of lesional T cells in psoriasis: intracel- lular cytokine and surface antigen expression indicates an acti- vated, memory/effector type 1 immunophenotype[J]. Arch Der- matol. Res., 2000, 292(10): 519-521.
31	SCHLAAK J F, BUSLAU M, JOCHUM W, et al.. T cells involved in psoriasis vulgaris belong to the Th1 subset[J]. J. Invest. Dermatol., 1994, 102(2): 145-149.
32	HURST S M, WILKINSON T S, MCLOUGHLIN R M, et al.. Il-6 and its soluble receptor orchestrate a temporal switch in the pattern of leukocyte recruitment seen during acute inflammation[J]. Immunity, 2001, 14(6): 705-714.
33	LANDE R, GREGORIO J, FACCHINETTI V, et al.. Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide[J]. Nature, 2007, 449(7162): 564-549.
34	ELLOSO M M, GOMEZ-ANGELATS M, FOURIE A M. Targeting the Th17 pathway in psoriasis[J]. J. Leukoc. Biol., 2012, 92(6): 1187-1197.
35	TEKIN N S, TEKIN I O, BARUT F, et al.. Accumulation of oxidized low-density lipoprotein in psoriatic skin and changes of plasma lipid levels in psoriatic patients[J/OL]. Med. Inflamm., 2007: 78454 [2022-06-25]. .
36	RASHMI R, RAO K S J, BASAVARAJ K H. A comprehensive review of biomarkers in psoriasis[J]. Clin. Exp. Dermatol., 2009, 34(6): 658-663.
37	GABR S A, AL-GHADIR A H. Role of cellular oxidative stress and cytochrome C in the pathogenesis of psoriasis[J]. Arch. Dermatol. Res., 2012, 304(6): 451-457.
38	SHINGU C, KOGA H, HAGIWARA S, et al.. Hydrogen-rich saline solution attenuates renal ischemia-reperfusion injury[J]. J. Anesth., 2010, 24(4): 569-574.

[1]	丁瑜, 赵博, 张瑾, 高旭栋. SIRT1去乙酰化修饰调控HMGB1介导的细胞焦亡在慢性鼻窦炎伴鼻息肉中的作用[J]. 生物技术进展, 2025, 15(3): 535-543.
[2]	赵天源, 王菁, 王雨露, 袁春森, 陈薛钗. 甜菜碱神经保护作用的研究进展[J]. 生物技术进展, 2025, 15(2): 220-225.
[3]	张若柳, 包明威. Toll样受体7在心血管疾病中的作用研究进展[J]. 生物技术进展, 2025, 15(2): 247-253.
[4]	刘昊, 李响. 冠状动脉疾病发病机制及治疗策略研究进展[J]. 生物技术进展, 2025, 15(2): 254-262.
[5]	李昌泽, 刘帅, 刁统祥, 张克勤, 孙鼎琪, 张辉. 发酵巴戟天对小鼠少弱精模型改善作用及机制研究[J]. 生物技术进展, 2025, 15(1): 170-175.
[6]	段兴鹏, 刘景丽, 王澈, 尚德静. 巨噬细胞清道夫受体与Toll样受体对Ox-LDL摄取和炎症的影响[J]. 生物技术进展, 2024, 14(4): 668-675.
[7]	梁一鹏, 王迪, 宋昊泽, 石莉红, 佟静媛. 生物信息学分析鉴定骨髓增殖性肿瘤发生发展的免疫调控因子[J]. 生物技术进展, 2024, 14(3): 492-500.
[8]	韦双, 高维崧, 窦金萍, 赵泽鹏, 刘兴健, 李轶女. 细胞焦亡分子机制及其调控[J]. 生物技术进展, 2023, 13(6): 868-874.
[9]	杨建鸿, 陈军, 李雪飞, 刘利君, 陈丽莉, 段昕所, 秦树存, 何磊. 氢分子在皮肤疾病治疗中的潜力与前景[J]. 生物技术进展, 2023, 13(6): 875-881.
[10]	朱钧锴, 葛玲智, 张超, 曹璨, 吴嘉惠, 穆震. 氢分子对咪喹莫特诱导的小鼠银屑病样皮损的抑制作用[J]. 生物技术进展, 2023, 13(6): 945-953.
[11]	李世明, 张鹏, 赵鹏翔, 谢飞, 陈晓萍, 刘梦昱. 氧化应激与废用性肌萎缩研究进展[J]. 生物技术进展, 2023, 13(4): 524-533.
[12]	曹丽, 罗顺, 邢世海, 仇金树, 蔺智勇, 林军, 孟旭, 刘峰. 山药提取物对CHO细胞生长及抗体表达的影响[J]. 生物技术进展, 2023, 13(3): 449-456.
[13]	张景怡, 姜雪, 马思禺, 冯智超, 仪杨, 马晨, 宋怡菲, 谢飞. 氢气对颅脑损伤的保护作用研究进展[J]. 生物技术进展, 2023, 13(2): 234-239.
[14]	曹静钰, 刘承梅, 祁晨旭, 杜开颜, 陈蒙, 侯思伟. Nrf2在脊髓损伤后铁死亡的研究进展[J]. 生物技术进展, 2023, 13(2): 240-246.
[15]	陈军, 秦树存, 何磊. 富氢盐水对咪喹莫特诱导小鼠银屑病的抑制作用[J]. 生物技术进展, 2022, 12(4): 503-509.

纳米气泡氢水处理对咪喹莫特诱导银屑病小鼠模型的影响

Effects of Pre-treatment of Nanobubble Hydrogen Water on the Mouse Psoriasis Induction by Imiquimod

RichHTML

PDF

可视化

摘要/Abstract

引用本文

使用本文

图/表 7

参考文献 38

相关文章 15

编辑推荐

Metrics

本文评价