ETHNOPHARMACOLOGICAL RELEVANCE:Houshiheisan (HSHS), a classical formula from the Synopsis of the Golden Chamber, is traditionally used for stroke and is known for its wind-dispelling and deficiency-tonifying properties. While HSHS has been confirmed to significantly reduce tissue necrosis following cerebral ischemia, its precise effects on post-ischemic angiogenic responses remain incompletely understood. AIM OF THE STUDY:This study aimed to investigate the effects of HSHS on post-ischemic angiogenic responses and to explore the underlying mechanisms. MATERIALS AND METHODS:For in vivo experiments, male Sprague-Dawley rats underwent permanent occlusion of the middle cerebral artery (MCAO) to establish an ischemic stroke model. HSHS was administered intragastrically at doses of 5.25 g/kg and 10.5 g/kg once daily for 7 days. Pathological changes were assessed using HE staining. Cortical vascular density after cerebral ischemia was evaluated by CD31 immunofluorescence staining. Western blot and qRT-PCR techniques were employed to examine the expression of miRNAs and proteins within the relevant signaling pathways. For in vitro studies, primary BMECs were cultured, and an oxygen-glucose deprivation (OGD) model was established. CCK-8, wound healing, and tube formation assays were utilized to detect the functions of BMECs. Lentiviral transfection was employed to inhibit miR-126 or overexpress miR-21, thereby investigating the mechanism by which HSHS enhances BMEC angiogenic activity. RESULTS:In vivo, HSHS attenuated vascular injury, increased cortical vascular density, and modulated the expression of angiogenesis-related proteins in the ischemic region. HSHS significantly elevated miR-126 expression in brain tissue while inhibiting the expression of its target gene PIK3R2. This was accompanied by increased PI3K expression and AKT phosphorylation. Additionally, HSHS decreased miR-21 expression in brain tissue and increased the expression of its target genes, Hmga2 and WWP1. These changes were associated with the downregulation of p16 and suppression of the TGF-β/SMAD7 signaling axis. In vitro, HSHS-serum enhanced the proliferation, migration, and tube formation of BMECs. Both miR-126 inhibition and miR-21 overexpression attenuated the HSHS-serum-induced angiogenic activity of BMECs. CONCLUSION:HSHS modulated post-ischemic angiogenic responses, a process that potentially involves miR-126/PIK3R2- and miR-21/Hmga2/WWP1-related regulation of BMEC function.

ETHNOPHARMACOLOGICAL RELEVANCE:Qing-Re-Chu-Shi Decoction (QRCSD), a traditional Chinese herbal formula, has been employed as a complementary and alternative therapy for inflammatory skin diseases. However, its active constituents and the mechanistic basis of its action on atopic dermatitis remain in adequately understood.AIM OF THE STUDY:Atopic dermatitis (AD) is an allergic dermatitis marked by eczematous lesions and pruritus. The study aimed to elucidate the underlying effects of QRCSD on AD and to identify the components responsible for its therapeutic efficacy in a mouse model.MATERIALS AND METHODS:Network pharmacology and UPLC-mass analysis were used to anticipate the pharmacological mechanisms and to identify active components of QRCSD, respectively. A DNCB-induced AD-like model was established in NC/Nga mice. QRCSD or prednisolone (as a positive control) was administered via gavage every other day from day14 to day 21. Dermatitis severity score, scratching behavior, skin barrier function, spleen index, Th1/Th2 lymphocyte ratio, and serum IgE levels were evaluated. Protein arrays, including 40 inflammatory cytokines, were performed on skin lesions, followed by confirmation experiments of Western blotting in dorsal skin lesions.RESULTS:The construction of a QRCSD-AD-Network and topological analysis firstly proposed potential targets of QRCSD acting on AD. Animal experiments demonstrated that oral administration of QRCSD ameliorated AD-like lesions, reduced epidermal thickness and mast cell count, decreased serum IgE levels, augmented tight junction protein (Claudin 1, Occludin) levels, and regulated the Th1/Th2 balance in the spleen, as well as spleen index. Elevated levels of interleukin (IL)-4, IL-5, IL-6, IL-17, and Eotaxin were revealed in AD-like skin lesions by protein arrays. Western blotting confirmed that the phosphorylation levels of ERK, P38, JNK, STAT3 and P65 were downregulated, and IL-6 expression was also reduced following QRCSD treatment.CONCLUSIONS:The study enhances the understanding of the anti-inflammatory and immunomodulatory effects of QRCSD, showcasing its significant protective role against atopic dermatitis. Treatment with QRCSD may be considered as a viable candidate for complementary and alternative therapy in managing atopic dermatitis.

Houshiheisan (HSHS), a classic prescription in traditional Chinese medicine (TCM), has shown outstanding efficacy in treating stroke. This study investigated various therapeutic targets of HSHS for ischemic stroke using mRNA transcriptomics. Herein, rats were randomly separated into the sham, model, HSHS 5.25 g/kg (HSHS5.25), and HSHS 10.5 g/kg (HSHS10.5) groups. Rats suffering from stroke were induced by permanent middle cerebral artery occlusion (pMCAO). After seven days of HSHS treatment, behavioral tests were conducted, and histological damage was examined with hematoxylin-eosin (HE). The mRNA expression profiles were identified using microarray analysis and quantitative real-time PCR (qRT-PCR) validated gene expression changes. An analysis of gene ontology and pathway enrichment was conducted to analyze potential mechanisms confirmed using immunofluorescence and western blotting. HSHS5.25 and HSHS10.5 improved neurological deficits and pathological injury in pMCAO rats. The intersections of 666 differentially expressed genes (DEGs) were chosen using transcriptomics analysis in the sham, model, and HSHS10.5 groups. The enrichment analysis suggested that the therapeutic targets of HSHS might regulate the apoptotic process and ERK1/2 signaling pathway, which was related to neuronal survival. Moreover, TUNEL and immunofluorescence analysis indicated that HSHS inhibited apoptosis and enhanced neuronal survival in the ischemic lesion. Western blot and immunofluorescence assay indicated that HSHS10.5 decreased Bax/Bcl-2 ratio and suppressed caspase-3 activation, while the phosphorylation of ERK1/2 and CREB was upregulated in a stroke rat model after HSHS treatment. Effective inhibition of neuronal apoptosis by activating the ERK1/2-CREB signaling pathway may be a potential mechanism for HSHS in the treatment of ischemic stroke.

【摘要】 目的 用数据挖掘技术分析慢性糜烂性胃炎的临床症状、常见证候及用药规律，形成理法方药融合统一的辨证论治思路。方法 检索中国知网（China National Knowledge Infrastructure，CNKI）、维普中文期刊服务平台维普中文期刊数据库（Chongqing VIP Information Company Limited，VIP)、万方数据知识服务平台（Wanfang Database）建库至2022年6月1日相关期刊文献中慢性糜烂性胃炎的症状与证型及治疗处方，利用古今医案云平台（V2.5）对慢性糜烂性胃炎的临床症状包括舌象、脉象、常见证候、证素特点及用药规律进行分析。结果 收集慢性糜烂性胃炎的医案207例，经过规范化处理后，高频出现的前五种症状依次为嗳气、口苦、纳差、口干、乏力；病性证素主要为湿和热；病位证素主要在于脾和胃；常见的中医证型为脾胃湿热证、脾胃气虚证、肝胃不和证、胃阴虚证4个类型，占所有证型的50%以上。通过证型与用药社团分析，脾胃湿热证用黄芩、黄连、半边莲等；脾胃气虚证用党参、白术、木香等；肝胃不和证用陈皮、郁金、枳实；胃阴虚证用天花粉、白芍、玉竹等。结论 慢性糜烂性胃炎以脾胃湿热为主要病机，病性以实证为主；清化湿热，调理气机可作为治疗本病的重要方法。临床上应根据症状进行辨证分型，根据分型结果进行处方用药，疗效最佳。

Background: At present, acupuncture-related practices have been widely used to treat psoriasis. In our study, we investigated the effect and explored the mechanism of electroacupuncture (EA) on acupoints Baihui (DU20) and Xuehai (SP10) for the treatment of psoriasis. Methods: Imiquimod-induced psoriasis-like mouse model was used in this study. Mice were treated with electroacupuncture at DU20 and SP10 (depth of 2-3 mm, frequency of 2/15 Hz, intensity of 0.5-1.0 mA, 10 min/day). The severity of psoriasis-like lesions for each group was assessed. In addition, histological analysis of the lesions were performed. The levels of inflammatory cytokines were determined using Elisa. The expression levels of Substance P (SP) and NK1R were measured using Western blotting. In addition, NK1R inhibitor was administrated to evaluate the target of electroacupuncture in our mouse model. Results: Electroacupuncture significantly alleviated IMQ-induced skin lesions and epidermal thickness, accompanied with reduced keratinocyte proliferation, CD3+, CD4+, and CD8+ T cells infiltration. The reduced levels of inflammatory cytokines was observed after electroacupuncture treatment. In addition, electroacupuncture inhibited the expression levels of SP and NK1R. NK1R inhibitor could ameliorate lesional symptoms and suppress epidermal thickening and CD3+, CD4+, and CD8 + T cell infiltration. Conclusions: Electroacupuncture relieved psoriasis-like inflammation and T cell infiltration. This therapeutic action was likely mediated by the modulation of Substance P and its receptor NK1R. (c) 2023 Center for Food and Biomolecules, National Taiwan University. Production and hosting by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).

目的 分析中医药治疗脑小血管病的组方用药规律.方法 检索中国期刊全文数据库、中文科技期刊数据库、中国学术期刊数据库建库至2021年8月相关期刊文献中治疗脑小血管病的内服方剂,采用中医传承辅助平台(V2.5)的关联规则分析、复杂系统熵聚类及无监督的熵层次聚类等方法进行分析.结果 共收集明确治疗脑小血管病的内服方剂95首,处方中使用频次大于等于10的中药有32味,复杂系统熵聚类得到4个新方.结论 脑小血管病的中医药治疗应攻补兼施,以活血化瘀通络治标的同时,还应重视益气、补肾等扶正药的使用.

Background Long non-coding RNAs (lncRNAs) are substantial to wide varity of biological processes and pathogenesis processes of ischemic stroke. Houshiheisan ( HSHS ), a typical prescription of traditional Chinese medicine, has outstanding efficacy in treating stroke, although the comprehensive molecular mechanism of its therapeutic effect has remained obscure up to now. Methods In this work, we induced a ischemic stroke rat model by permanent middle cerebral artery occlusion (MCAO). The microarray expression profile of lncRNAs and mRNAs was used to investigate various possible roles and molecular mechanism of HSHS in treating MCAO rats. Results HSHS improved the neurological deficit and alleviated the pathological damage after cerebral ischemia. The Clariom D Assay (rat, Affymetrix) showed that 8128 mRNAs and 3022 lncRNAs differentially expressed between sham group and model group, and 868 mRNAs and 836 lncRNAs between HSHS and model groups. Among the three groups, the intersections (666 mRNAs and 288 lncRNAs) were chosen and analyzed. GO and KEGG analysis disclosed that the majority of overlapping mRNAs were enriched in Axon guidance, Autophagy, PI3K-AKT signaling pathway and mTOR signaling pathway. Pathway network, protein-protein network and molecular complex detection analysis identified significant hub genes, e.g., Rock2, Rps6kb1, Wnt4, IL-6 and so on. Furthermore, we explored dynamic interactions between the dysregulated lncRNAs and mRNAs by lncRNA-mRNA network analysis. Finally, qRT-PCR verified expressions of the critical differentially expressed lncRNAs and mRNAs within the three groups. Conclusion Our results indicate that these differentially expressed lncRNAs may affect pathological processes of ischemic stroke by regulating co-expressed mRNAs, providing novel insight in regarding lncRNAs’ involvement in the treatment of ischemic stroke.

BACKGROUND:psoriasis is a chronic inflammatory skin disease. The accumulation of IL-17 cytokines in the lesions leads to epidermis proliferation. Traditional Chinese medicine has a significant effect on psoriasis treatment. Among them, Tuhuaiyin is a representative prescription, which has an outstanding curative effect in acute and remission stage.METHODS:To reveal the target and molecular mechanism of Tuhuaiyin, systematic pharmacology platform and database screening were used to construct the Tuhuaiyin interaction network with compounds, targets and diseases. The intervention of Tuhuaiyin on keratinocyte proliferation and inflammation was verified in the model of psoriasis-like lesions induced by imiquimod. The effect on the number and function of IL-17-producing cells was detected, and the regulatory effect of Tuhuaiyin on gut microbial was explored.RESULTS:32 selected active molecules in Tuhuaiyin acted on psoriasis biological processes. Tuhuaiyin significantly alleviates erythema and scales in the psoriasis like mouse model induced by imiquimod. Excessive proliferation of keratinocytes and infiltration of inflammatory cells were restrained in the dermis by using Tuhuaiyin. The expression of IL-17 was down-regulated in skin and peripheral blood. The proportion of IL-17-producing cells was decreased in immune organs. And phosphorylation of JNK inhibited in skin lesions. At the same time, the change of gut microbial diversity in the psoriasis-like model was improved.CONCLUSION:our study predicted and verified the molecular immunological mechanism of Tuhuaiyin, alleviated the abnormal proliferation of keratinocytes by inhibiting the proportion of IL-17-producing cells and the expression of IL-17 cytokines. Taken together, our data identify the therapeutic potential of Tuhuaiyin for psoriasis.

目的:通过对比凉血解毒方,观察活血解毒方对咪喹莫特诱导的银屑病样小鼠皮损紧密连接蛋白表达以及皮损复发的干预作用,为中医药通过调节皮肤屏障治疗及延缓银屑病复发提供生物学证据.方法:选用C57BL/6J小鼠,随机分为空白对照组、模型组、阳性药(氨甲蝶呤)组、活血解毒方组和凉血解毒方组,小鼠背部剃毛后给予咪喹莫特涂抹诱导银屑病样皮损模型.初次干预7 d后,间隔30 d,除空白对照组外各组仅涂抹咪喹莫特诱导银屑病复发皮损模型.期间对皮损拍照并进行银屑病面积和严重程度指数(PASI)评分;水油笔检测皮损表皮含水量;HE染色观察其病理改变并测量表皮厚度;免疫荧光法检测小鼠表皮Ki67表达;免疫组化法检测表皮兜甲蛋白(loricrin),真皮中紧密连接蛋白claduin-1、claudin-7和occludin的表达及CD3+T淋巴细胞浸润.Western blot法检测皮损occludin的表达.结果:活血解毒方可缓解咪喹莫特诱导的小鼠银屑病样皮损,降低PASI评分及表皮厚度(P<0.05);与模型组比较,活血解毒方可增加皮损区表皮水分含量(P<0.05),减少表皮Ki67和loricrin的异常表达和真皮CD3+T细胞浸润(P<0.01),增加claudin-1、claudin-7和occludin的表达(P<0.05),增强紧密连接的结构完整性.活血解毒方亦可减轻二次诱导的小鼠银屑病样皮损表现,降低PASI评分及表皮厚度(P<0.05).结论:活血解毒方可能通过调节紧密连接蛋白表达,恢复受损的表皮屏障功能,从而减轻银屑病复发皮损表现.

Background: Psoriasis is a psychosomatic immune skin disease with psychological factors contributing to the disease. Substance P (SP) is highly expressed in the psoriatic lesions of patients and is involved in pathological disease progression. Tribulus terrestris L. has been used as a Chinese herbal medicine for disease prevention for thousands of years. Terrestrosin D (TED) has been identified as the effective monomeric component of Tribulus terrestris L..Purpose: We investigated whether TED could reverse imiquimod-induced psoriatic lesions, and then, investigated its potential mechanism of action both in vivo and in vitro.Methods: 5% imiquimod cream was applied onto the backs of mice for 6 days to induce psoriasis-like skin lesions. The psoriatic area and severity index (PASI) was then used for scoring disease severity. Pathological changes and Ki-67 expression levels in skin lesions were measured using hematoxylin and eosin (H & E) and immunofluorescence staining after TED administration. The in vivo and in vitro expression levels of inflammatory cytokines, the ratio of DCs, and SP were measured using ProcartaPlex Mouse Cytokine panels, flow cytometry, and western blotting. Behavioral assessments were determined using the open field and elevated plus-maze (EPM) test.Results: TED decreased PASI scores, epidermal thickness, Ki-67 expression levels, the ratio of DCs in the spleen, and secretion of IL-12p70, IL-18, and TNF-alpha in imiquimod-induced psoriasis-like murine models. Furthermore, TED increased IL-10 secretion levels, improved behavior, and down-regulated the expression levels of SP. Additionally, TED inhibited the in vitro maturation and activation of SP-induced CD11c(+) DCs and the release of IL-12p70 and IL-23.Conclusion: TED reduced DCs maturation, down-regulated the expression levels of inflammatory factors, and improved skin lesions and behavior of psoriasis-like murine models by inhibiting the interaction between Substance P and Dendritic cells.

目的 总结纳米ATO的制备方法以及应用等最新研究进展.方法 分别从液相法、固相法、气相法等三大类对纳米ATO的制备方法优缺点进行阐述总结,并结合ATO的透光和隔热特点对其应用现状进行详细描述.结果 液相法所制备的纳米ATO纯度高、均匀性好,是目前制备纳米ATO最常用的方法,并在特种包装以及隔热薄膜和涂层等领域具有重要应用.结论 化学接枝和结构改性能改善纳米ATO粒子在聚合物材料中的分散,可以进一步改善和拓宽纳米ATO的应用范围,这也是未来纳米ATO研究的重要发展方向之一.

目的:通过建立脾虚-银屑病样复合小鼠模型探讨脾虚对银屑病皮损及分子机制的影响.方法:苦寒泻下结合营养限制法建立脾虚证模型后,咪喹莫特乳膏局部涂抹诱导银屑病样模型.观察小鼠皮损面积和疾病严重程度(PASI)及其组织形态学变化;免疫组织化学法检测皮损中增殖细胞核抗原(PCNA)和CD3的表达;RT-PCR技术检测皮损中FOXP3、ROR-γt、白细胞介素2(IL-2)基因表达水平.结果:与对照-IMQ组比较,脾虚-IMQ组小鼠皮损鳞屑和表皮厚度明显升高(P＜0.05),炎性细胞浸润显著,皮损中ROR-γtmRNA表达的升高趋势有所减缓,但Foxp3 mRNA显著降低(P＜0.05).结论:脾虚可加重银屑病皮损的严重程度,尤其鳞屑增多、皮损肥厚,与脾虚血燥的临床表现较一致,探索其机制可能与Treg/Th 17平衡偏移有关.

Psoriasis is not only a chronic inflammatory skin disease but also a psychosomatic disorder. Depression is one of the most common associated diseases, which aggravates psoriatic skin lesions and affects the life quality of patients. Clinical experiments establish a correlation between psoriasis and depression; however, the mechanisms yet unclear because only a few related studies are available. Therefore, to investigate whether imiquimod-induced psoriasis-like mice showed depressive-like behavior, 5% imiquimod cream was smeared on the back of mice to induce psoriasis-like skin lesions for 8 days. Consequently, the psoriasis area and severity index (PASI) score, epidermal thickness, expression of Ki67 and CD3(+) T lymphocyte, the content of IL-12p70, IL-17A, and IL-23 in skin lesions were increased. The psoriasis-like mice presented significant changes in body mass. The sugar water preference rate, the central area distance and area time, and the content of 3,4-dihydroxyphenylaceticacid (DOPAC) and noradrenaline (NE) in the prefrontal cortex, 5-hydroxytryptamine (5-HT), adrenaline (Ad), and DOPAC in the hippocampus, and Ad and gamma-aminobutyric acid (GABA) in the hypothalamus of psoriasis-like mice were significantly decreased. The results showed that after the application of imiquimod, depressive-like behaviors appeared in psoriasis-like mice, and the secretion of related neurotransmitters was disordered. Thus, these mice could be used as animal models for studying psoriasis complicated with depression symptoms.

INTRODUCTION:The incidence of psoriasis vulgaris is increasing worldwide. Chronic recurrence of the disease, as well as accompanying cardiovascular disease, metabolic syndrome, and depression has affected the physical and mental health of these patients. Psoriasis vulgaris is a difficult and major disease in the dermatology field. Short-term curative effects using conventional therapy for psoriasis vulgaris has made major strides. However, traditional Chinese medicine (TCM) treatment has long-term curative advantages for psoriasis vulgaris but lacks the scientific and clinical evidence for its use. This study intends to demonstrate and provide scientific and clinical evidence for the use of TCM to delay the recurrence of psoriasis vulgaris.METHODS AND ANALYSIS:This will be a prospective, multicenter cohort study. We intend to recruit 1521 psoriasis vulgaris patients from 14 hospitals in Beijing, Tianjin, and Hebei. Treatment will be based on the diagnosis specifications and clinical practice guidelines of TCM and conventional therapy. During inclusion and the subsequent follow-up period, doctors through electronic case reports will collect different therapeutic TCM regimens and conventional therapy that were administered. Information on life condition, skin lesions at each visit, World Health Organization Quality of Life Instruments, Zung Self-rating Anxiety Scale, Zung Self-assessment of Depression, laboratory examinations, incidence of new rash and recurrence during the remission and recurrence stages will be recorded.ETHICS AND DISSEMINATION:The clinical trial protocol for this study was approved by the ethics committee of the Beijing hospital of TCM affiliated to capital medical university (Ethics number: 2019BL02-010-02). We will publish and present our results at national and international conferences and in peer-reviewed journals specialized in dermatology.TRIAL REGISTRATION:This protocol has been registered in clinicaltrials. gov (ChiCTR1900021629).

目的:观察银屑病样小鼠皮损紧密连接蛋白中水闸蛋白(claduin-1,claudin-7),闭锁蛋白(occludin)的表达,明确养血解毒方对银屑病表皮通透屏障的修复作用,为养血解毒方治疗银屑病提供科学依据.方法:将C57BL/6J小鼠随机分为空白组、模型组、甲氨喋呤组、养血解毒方组,制备甲氨喋呤溶液、养血解毒方水煎剂对应灌胃干预,同时小鼠背部剃毛后给予咪喹莫特涂抹诱导银屑病样皮损模型.每日拍照记录皮损形态并对严重程度指数(PASI)评分;水油测试笔检测皮损表皮含水量;苏木素-伊红(HE)染色观察其病理改变、测量表皮厚度;免疫荧光法检测增殖相关的核抗原(Ki67);免疫组化法检测表皮兜甲蛋白(loricrin),真皮中CD3+T淋巴细胞浸润和紧密连接蛋白claduin-1,claudin-7,occludin的表达;蛋白免疫印迹法(Western blot)检测皮损中claudin-7,occludin的表达.模拟银屑病皮损微环境,建立白细胞介素-17(IL-17,1 mg·L-1)刺激的角质形成细胞(Hacat)模型,制作养血组分、解毒组分、养血解毒方喷干粉进行干预.采用细胞增殖毒性检测试剂盒-8(CCK-8)法检测药物对Hacat细胞的毒性;细胞免疫荧光法检测药物对角质形成细胞claudin-1,claudin-7,occludin表达的干预作用.结果:与模型组比较,养血解毒方可显著减轻小鼠银屑病样皮损表现,降低PASI评分及皮损表皮厚度(P＜0.01),增加皮损区表皮水分含量(P＜0.01),减少表皮ki67,loricrin的异常表达和真皮CD3+T细胞浸润(P＜0.01),并增加紧密连接蛋白claudin-1,claudin-7,occludin的表达(P＜0.05),增加紧密连接结构的完整性;体外研究发现,与模型组比较,养血解毒方组和养血组分组明显升高紧密连接蛋白claudin-1,claudin-7,occludin的表达(P＜0.05);与模型组比较,解毒组分组蛋白表达水平无统计学差异.结论:养血解毒方通过调节角质形成细胞间紧密连接的表达抑制其异常的增殖分化过程,进一步恢复破坏的表皮通透屏障,可能是其治疗银屑病的作用机制之一.其中养血解毒方的养血组分对调节紧密连接的修复起主要作用.

目的:观察清肝凉血解毒汤对咪喹莫特诱导的银屑病样小鼠模型皮损的影响.方法:72只BALB/c雄性小鼠,背部刮毛,随机分为空白对照组(Control,C)、模型组(Model,M)、复方高、中、低剂量组(Q-H、Q-M、Q-L)和甲氨蝶呤组(MTX),5％咪喹莫特乳膏(IMQ)背部涂抹诱导皮肤银屑病样模型.采用银屑病皮损面积和疾病严重程度(Psoriasis area and severity index,PASI)每日进行评分,光镜下观察皮损组织形态学变化及表皮厚度;免疫组化法检测皮损中增殖细胞核抗原(PCNA)和T淋巴细胞表面标志CD3表达情况;免疫荧光法检测皮损中CD11c+树突状细胞、CGRP、NK1R表达情况;采用实时PCR技术检测皮损中IL-1β、IL-12、IL-23mRNA表达水平;Western Blot法检测皮损中NPY、SP蛋白表达情况.结果:M组小鼠皮损上鳞屑厚,浸润明显,红斑重;其余各组皮损均较M组轻.与C组相比,M组表皮厚度、PCNA、CD3+ T细胞及CD11c+细胞均明显增多(P＜0.01);复方各剂量组与M组相比,表皮薄,PCNA、CD3+及CD11c+细胞表达个数均明显减少.M组与C组相比,CGRP、NK-1R、IL-1β、IL-12、IL-23mRNA表达均上调(P＜0.05),而余组与M组相比,上述指标的表达均明显下调(P＜0.05).与C组相比,M组小鼠皮损中NPY的表达增高(P＜0.05),MTX、Q-M、Q-L组表达量较M组低(P＜0.05);M、MTX、Q-M、Q-L组皮损中SP的表达均呈增高趋势,但组间相比无统计学差异.结论:清肝凉血解毒汤可通过下调NK-1R、NPY、CGRP的表达水平改善小鼠银屑病样皮损,降低表皮细胞的异常增殖、减轻炎症细胞的浸润,减少皮肤中CD11c+树突状细胞数量,下调IL-1β、IL-12、IL-23细胞因子的表达水平.

目的 观察搜风顺气丸对咪喹莫特诱导的银屑病样小鼠模型皮损的影响.方法 40只雄性BALB/c小鼠,背部备皮后,采用数字表法随机分为空白对照组、模型组、搜风顺气丸组和甲氨蝶呤组,背部涂抹5％(质量分数)咪喹莫特乳膏诱导银屑病样模型.采用银屑病皮损面积和疾病严重程度评分(psoriasis area and severity index,PASI)标准进行评分,测量表皮层厚度,记录形态学变化;免疫荧光染色观察小鼠皮损中Ki-67的表达;免疫组织化学检测皮损CD3+T淋巴细胞的表达;流式细胞术检测胸腺及双侧腹股沟淋巴结CD3+T细胞中CD4+、CD8+、γδT+及RORγt+γδT+细胞比例;Western blotting法检测小鼠皮损中磷酸化信号转导与转录激活因子3(phosphorylated-signal transduction and activators of transcription 3,p-STAT3)蛋白的表达水平.结果 与模型组相比,搜风顺气丸组小鼠皮损PASI评分及表皮厚度均明显降低、脾指数(P＜0.01),胸腺指数及淋巴结指数(P＜0.01)均明显低于模型组、Ki-67阳性细胞表达个数减少(P＜0.01);真皮CD3+T细胞表达均低于模型组(P＜0.01);双侧腹股沟淋巴结及胸腺CD3+T细胞中CD4 +T细胞比例差异无统计学意义,但γδT+及RORγt+ γδT+细胞比例均明显减少;并且搜风顺气丸组小鼠皮损中p-STAT3表达下降(P＜0.01).结论 搜风顺气丸可能通过抑制RORγt的表达作用,从而减少IL-17A的分泌,改善皮损,表明搜风顺气丸对炎性因子的抑制作用可能是其治疗银屑病的机制之一.

目的:观察逍遥散对咪喹莫特诱导的银屑病样小鼠模型皮损及抑郁神经递质的干预作用.方法:36只BALB/c雄性小鼠,背部备皮后,随机分为空白对照组、模型组、甲氨蝶呤组和逍遥散高、中、低剂量组,每组6只,除对照组外,其余各组小鼠均用5％咪喹莫特乳膏背部涂抹诱导银屑病样皮损.采用银屑病皮损面积和疾病严重程度(psoriasis area and severity index,PASI)每日进行评分;糖水偏好实验探究小鼠行为学差异;光镜下观察皮损组织形态学变化及表皮厚度;免疫组化法检测皮损组织中T淋巴细胞表面标志物CD3的表达情况;免疫荧光法检测皮损组织中Ki67的表达情况;液相色谱-质谱联用技术检测小鼠海马区和下丘脑区脑组织肾上腺素(adrenaline,AD)、γ-氨基丁酸(γ-aminobutylic acid,GABA)、谷氨酸(glutamate,Glu)、多巴胺(dopamine,DA)及其代谢产物等单胺类神经递质的含量.结果:逍遥散各剂量组和甲氨蝶呤组背部皮损较模型组有明显改善,PASI评分和表皮厚度均显著低于模型组(P<0.05);逍遥散各剂量组和甲氨蝶呤组皮损中Ki67和CD3+T细胞的水平均较模型组显著降低(P<0.05);空白对照组及逍遥散高剂量组小鼠体质量变化幅度显著小于模型组(P<0.05);空白对照组糖水偏好率显著高于模型组(P<0.01),甲氨蝶呤组和逍遥散各剂量组糖水偏好率与模型组相比有一定升高趋势,但差异无统计学意义;空白对照组小鼠海马区3,4-二羟基苯乙酸(3,4-Dihydroxyphenylacetic acid,DOPAC)、AD、GLU和GABA含量较模型组显著降低(P<0.05),DA和高香草酸(homovanillic acid,HVA)的含量较模型组无显著差异(P>0.05);空白对照组小鼠下丘脑区AD和GABA的含量较模型组显著降低(P<0.05),DA、DOPAC、HVA和GLU的含量较模型组无显著差异(P>0.05);逍遥散高剂量组下丘脑区AD的含量较模型组显著增多(P<0.01),逍遥散低剂量组下丘脑区HVA的含量较模型组显著增多(P<0.01).PASI评分与海马区DOPAC、AD、GLU和GABA的含量及下丘脑区AD、GLU和GABA的含量呈负相关,即小鼠背部皮损越严重,抑郁相关神经递质表达量越低,表明小鼠抑郁程度加重.结论:逍遥散可以改善咪喹莫特诱导的银屑病样小鼠皮损,并改善其抑郁行为学,上调抑郁症相关单胺类神经递质的表达水平;咪喹莫特诱导的银屑病样小鼠皮损与抑郁相关神经递质的表达呈负相关,其抑郁程度随银屑病皮损的加重而加重.

目的:建立脾虚银屑病样小鼠模型,观察健脾养血解毒方对其银屑病样皮损的干预作用,并探讨其作用机制.方法:首先采用苦寒泻下结合营养限制法建立脾虚小鼠模型,持续15 d后检测验证,将脾虚小鼠随机分为单纯脾虚组(脾虚-Ctr)、脾虚银屑病样组(脾虚-IMQ)、阳性对照组(脾虚-MTX)和健脾养血解毒方高、中、低剂量组(JPYXJD-H,M,L),采用咪喹莫特诱导-银屑病样模型.观察各组小鼠皮损面积和疾病严重程度(psoriasis area and severity index,PASI),每日拍照记录;治疗后第6天取材,计算脾脏及淋巴结指数;光镜下观察皮损组织形态学变化及表皮层厚度;免疫组织化学法检测皮损中PCNA和CD3的表达;流式细胞术检测小鼠淋巴结中Treg和Th17细胞数量;RT-PCR技术检测皮损中IL-17A、IL-23、FOXP3、ROR-γt等相关基因表达水平;采用Western Blotting法检测pSTAT3、PPAR-γ通路蛋白表达水平.结果:(1)与对照组小鼠相比,脾虚组表观指征异常明显,血清中D-木糖含量明显降低(P＜0.05).(2)与脾虚-Ctr组相比,脾虚-IMQ组小鼠皮损PASI评分及表皮厚度明显增加,皮损部位PCNA、CD3阳性个数显著增多,IL-17、IL-23、ROR-γt和IFN-γ等炎症因子的表达明显升高,pSTAT蛋白表达升高而PPAR-γ蛋白表达降低的趋势明显.JPYXJD-H、M、L组与其相比各项指标均有不同程度改善,其中以JPYXJD-L组最为显著.结论:健脾养血解毒方在传统理血解毒的基础上强调健脾治法,并依此增加健脾药的使用,从而发挥对脾虚证-银屑病复合模型小鼠皮损的干预作用,通过PPAR-γ/pSTAT3通路调节Treg/Th17之间的免疫平衡可能是其有效作用机制之一.

目的:观察清肝凉血解毒方(QGLXJD)、凉血活血方(LXHX)对咪喹莫特诱导的银屑病样小鼠行为学及神经肽Y(NPY)表达的影响.方法:30只BALB/c雄性小鼠,剔除背部毛发,随机分为空白对照组(C)、模型组(M)、清肝凉血解毒方组(QG)、凉血活血方组(LX)和甲氨蝶呤组(MTX).背部涂抹5％咪喹莫特乳膏(IMQ)诱导皮肤银屑病样模型.采用银屑病皮损面积和疾病严重程度(Psoriasis area and severity index,PASI)每日进行评分,分别运用旷场及高架十字迷宫评价各组小鼠行为学差异,HE染色后光镜下测量表皮厚度;免疫组化法检测皮损中T淋巴细胞表面标志CD3+及表皮中增殖细胞核抗原(PCNA)表达情况;采用实时PCR技术检测皮损中IL-23、IL-1 β、IL-12 mRNA表达水平;Western blot法检测皮损中NPY蛋白表达情况.结果:与C组相比,M组表皮厚度、PCNA、CD3+T细胞、IL-1 β、IL-12、IL-23 mRNA表达均增加(P＜005);其余组与M组相比,表皮薄,PCNA、CD3+T细胞、IL-1 β、IL-12、IL-23 mRNA表达水平均降低(P＜0.05).与C组比较,银屑病样小鼠焦虑水平高,以M组最为明显;QG组与M组比较,焦虑水平低,而LX组与QG组比较,焦虑水平高;NPY在M组中表达最多,在LX、QG、C组表达依次减少.结论:清肝凉血解毒方能改善银屑病样小鼠的焦虑行为,下调NPY的表达水平,从整体角度改善小鼠银屑病样皮损.