湿疹及皮炎

咪唑斯汀、氯雷他定及西替利嗪对小鼠变应性接触性皮炎作用的比较研究，咪唑斯汀等几种抗组胺药对小鼠接触性皮炎作用的实验研究，0．05％卤米松霜对小鼠接触性皮炎的作用，信阳地区385例接触性皮炎及湿疹患斑贴试验结果分析，脐部皮炎138例斑贴试验结果临床分析，     

某些炎症介质拮抗剂抗过敏作用的实验研究

目的：为了探讨抗组胺药及抗５ 羟色胺（５ ＨＴ）药对迟发型超敏反应（ＤＨＲ）的作用及其机制。方法：我们观察了扑尔敏、特非那丁、多虑平、利血平、赛庚啶、苯噻啶对小鼠变应性接触性皮炎（ＡＣＤ）及真皮肥大细胞（ＭＣ）、表皮郎格罕细胞（ＬＣＳ）的影响。结果：发现这６种药物对小鼠ＡＣＤ均有不同程度的抑制作用，提示这些药物的抗过敏作用不限于Ⅰ型变态反应疾病，对Ⅳ型变态反应疾病亦可有效。受试药物中扑尔敏、特非那丁、多虑平、利血平、赛庚啶等５种能减少真皮ＭＣ数，扑尔敏、多虑平、利血平等３种能减少表皮ＬＣＳ数。结论：提示这些药物抑制ＤＨＲ的机制至少部分地与减少真皮ＭＣ数及／或减少表皮ＬＣＳ数有关。     

3种抗组胺药抗组胺及抗花生四烯酸作用的比较研究

目的:比较咪唑斯汀、氯雷他定、西替利嗪3种抗组胺药的抗组胺及抗花生四烯酸的作用。方法:给大鼠左、右爪分别皮下注射花生四烯酸(1.0g/L,0.1mL)和组胺(10g/L,0.1mL)构建鼠爪水肿炎性模型。在注射花生四烯酸和组胺2h前分别给予咪唑斯汀、氯雷他定、西替利嗪(0.6mg/kg)灌胃,注射后应用体积测量仪分别测定给药后鼠爪体积在不同时间点的变化。结果:咪唑斯汀可抑制花生四烯酸所致的鼠爪水肿(P<0.05),西替利嗪、氯雷他定对其无明显抑制作用;咪唑斯汀对组胺所致的鼠爪水肿有抑制作用(P<0.05),抑制作用强于氯雷他定组,但与西替利嗪组比较无统计学差异(P>0.05)。结论:咪唑斯汀具有抗组胺和抗花生四烯酸的作用,且其抗组胺作用强于氯雷他定;与氯雷他定、西替利嗪相比,咪唑斯汀表现出其独特的抗花生四烯酸的作用。     

咪唑斯汀对小鼠变应性接触性皮炎的作用及与血清白三烯的关系

为研究咪唑斯汀对小鼠变应性接触性皮炎(ACD)的疗效,分析咪唑斯汀与血清白三烯的相关性。建立小鼠ACD疾病模型,观察咪唑斯汀在不同时间点对小鼠ACD炎症性肿胀的治疗作用;同时使用酶联免疫法检测血清白三烯C4(LTC4)水平并进行相关分析。咪唑斯汀对小鼠ACD的炎症性肿胀具有显著迅速地抑制作用;而且其皮肤肿胀度与血清LTC4水平呈正相关。咪唑斯汀对小鼠变应性接触性皮炎有很好的治疗作用,其机制可能是抑制5-脂氧合酶的活性,继而阻止白三烯的产生而发挥其抗炎活性。     

咪唑斯汀、氯雷他定及西替利嗪对小鼠变应性接触性皮炎作用的比较研究

目的:比较咪唑斯汀、氯雷他定及西替利嗪对小鼠变应性接触性皮炎(ACD)的抑制作用。方法:建立小鼠ACD模型,采用致敏前及诱发后两种给药方法,口服不同剂量咪唑斯汀、氯雷他定及西替利嗪,观察抑制作用。结果:致敏前开始给药,3种药物均能明显抑制ACD小鼠耳肿胀(P<0.05),但咪唑斯汀的抑制作用强于氯雷他定及西替利嗪(P<0.05);诱发后开始给药,咪唑斯汀组小鼠耳肿胀消退快于氯雷他定及西替利嗪(P<0.05)。结论:咪唑斯汀对小鼠ACD抑制作用强于氯雷他定和西替利嗪。     

新一代抗组胺药对变应性接触性皮炎小鼠3种细胞因子影响的比较研究

目的:研究咪唑斯汀、氯雷他定及西替利嗪对变应性接触性皮炎(allergiccontactdermatitis,ACD)小鼠产生干扰素(IFN)、肿瘤坏死因子(TNF)及白介素(IL)-4的影响,探讨抗组胺药治疗ACD的作用机制。方法:建立小鼠ACD模型,采用ELISA法检测ACD小鼠产生IFN-γ、TNF-α和IL-4的水平及3种药物分别对它们的作用。结果:ACD小鼠血清及脾淋巴细胞IFN-γ水平均明显升高(P<0.01);血清TNF-α水平明显升高(P<0.01),腹腔巨噬细胞产生TNF-α水平无明显变化(P>0.05);血清及脾淋巴细胞产生IL-4水平无明显变化(P>0.05)。咪唑斯汀对血清及细胞培养液中3种细胞因子的水平均有显著或不同程度的抑制作用,而氯雷他定、西替利嗪仅对部分细胞因子产生一定的抑制作用。结论:咪唑斯汀对ACD小鼠产生的3种细胞因子的抑制作用强于氯雷他定和西替利嗪。它们对ACD小鼠3种细胞因子的抑制作用与临床疗效的关系有待进一步研究。     

咪唑斯汀对花生四烯酸诱导的鼠爪水肿的影响

目的 探讨咪唑斯汀抗炎活性的产生机制。方法 大鼠鼠爪皮下注射0.1 mL的花生四烯酸(体积分数为0.003)诱导鼠爪水肿炎性动物模型。注射前灌胃分别给予咪唑斯汀、氯雷他定、西替利嗪(0.3 mg/kg),用千分尺测量肿胀足爪厚度,比较不同抗组胺药对鼠爪肿胀抑制程度的高低。分别给予大鼠5-脂氧合酶的直接抑制剂齐留通(3 mg/kg)和咪唑斯汀(0.3 mg/kg),比较2种药物对鼠爪肿胀抑制程度的高低。结果 咪唑斯汀显著抑制花生四烯酸诱导的鼠爪水肿,氯雷他定、西替利嗪对鼠爪水肿无抑制作用(P<0.01);齐留通显著抑制鼠爪水肿(P<0.01),对鼠爪水肿的抑制率与咪唑斯汀比较差异无显著性(P>0.05)。结论 咪唑斯汀可能通过抑制5-脂氧合酶活性的途径发挥其抗炎活性。     

咪唑斯汀抗炎活性的动物实验研究

目的:评价抗组胺剂量下咪唑斯汀的抗炎强度,探讨咪唑斯汀抗炎活性的产生机制。方法:给大鼠鼠爪皮下注射花四烯酸0.1mL(1.0g/L)或1%角叉菜胶0.15mL致炎剂,分别构建鼠爪水肿炎性模型,并在注射致炎剂2h前分别给予咪唑斯汀(0.3mg/kg)和西替利嗪(0.3mg/kg)灌胃,注射致炎剂后1、2、3、4h,应用体积测量仪测定给药后鼠爪体积的改变。结果:咪唑汀显著抑制花生四烯酸诱导的鼠爪水肿(P<0.05),对角叉菜胶诱导的鼠爪水肿无抑制作用(P>0.05);西替利嗪(0.3mg/kg)对种致炎剂诱导的鼠爪水肿均无抑制作用(P>0.05)。结论:抗组胺剂量的咪唑斯汀在动物体内具有较高的抗炎活性,咪唑斯汀能通过抑制5-脂氧合酶活性的途径发挥其抗炎活性。     

3种抗组胺药抗花生四烯酸致炎性的比较

目的:观察不同抗组胺药是否具有抗炎作用。方法:给大鼠鼠爪皮下注射花生四烯酸(1.0 g/L,0.1 mL)构建鼠爪水肿炎性模型,在注射花生四烯酸2 h前分别灌胃给予咪唑斯汀、地氯雷他定、依巴斯汀3种抗组胺药(0.3 mg/kg),注射后1、2、3、4h,应用体积测量仪分别测定给药后鼠爪体积的改变。结果:咪唑斯汀(0.3 mg/kg)显著抑制花生四烯酸诱导的鼠爪水肿(P<0.05),地氯雷他定、依巴斯汀对花生四烯酸诱导的鼠爪水肿均无抑制作用(P>0.05)。结论:0.3 mg／kg的咪唑斯汀在体内具有抗炎作用,相同剂量的地氯雷他定、依巴斯汀无抗炎作用。     

咪唑斯汀在治疗荨麻疹中具有双重活性

咪唑斯汀是一种新的第二代抗组胺药 ,是抗 5 -脂氧合酶活性的H1受体的拮抗剂 ,具有起效快、作用强、副作用少的特点。本文对荨麻疹的发病机理、咪唑斯汀治疗荨麻疹的疗效、与其他抗组胺药的比较及咪唑斯汀的长期作用等方面作了介绍。     

Inflammation-inhibiting effect of magnesium ions in contact eczema reactions

Water containing high concentrations of magnesium ions (e.g. Dead Sea water) is effective in the treatment of inflammatory skin diseases. Therefore, we examined the influence of Mg2+ on inflammation in allergic contact dermatitis induced by 1-chloro-2,4-dinitrobenzene (DNCB) in BALB/c mice. Animals challenged with 0.125% DNCB in the presence of magnesium chloride (28% and 14%) demonstrated significantly less pronounced contact dermatitis (ear swelling) than did animals challenged with DNCB alone (p less than 0.001 and p less than 0.01). In mice challenged with DNCB in combination with sodium chloride (14%) there was no statistically significant difference in the degree of ear swelling. These results were borne out in 5 patients known to be allergic to nickel, in whom magnesium chloride but not sodium chloride, suppressed nickel sulphate-induced contact dermatitis.     

Cytochemical and Ultrastructural Studies of the Langerhans' Cells

Abstract: In the guinea pig, experimental allergic contact dermatitis (ACD) And primary irritant contact dermatitis (PICD) were induced with different concentrations of dinitrochlorobenzene (DNCB). The epidermal Langerhans' cells (LCs) were observed sequentially by both adenosine triphosphatase (ATPase) and electron microscopy. Light microscopically, in ACD, the density and dendritic processes of LC decreased markedly within 12 h after antigen challenge. Almost no recognization LCs could be seen within 2 to 5 days. Later, LCs began to repopulale in the epidermis. Within 14 days, the density and shape of the LCs returned to normal. On the contrary, LCs changed more rapidly in PICD. The dendritic processes of LC decreased within 2 h and cell density decreased dramatically within 6 h after DNCB application. LCs also repopulated more rapidly in the epidermis. Electron microscopically, in ACD, we observed that lymphocyte-like cells apposed to LCs; LCs were activated and damaged; however, in PICD, we found neither the apposition of lymphocyte-like cells to LCs, nor the activation of LCs. LCs play an important role in the convalescence phase as well as in the early and later phases of contact allergic reaction.     

Cytochemical and Ultrastructural Studies of the Langerhans'' cells

In the guinea pig, experimental allergic contact dermatitis (ACD) and primary irritant contact dermatitis (PICD) were induced with different concentrations of dinitrochlorobenzene (DNCB). The epidermal Langerhans' cells (LCs) were observed sequentially by both adenosine triphosphatase (ATPase) and electron microscopy. Light microscopically, in ACD, the density and dendritic processes of LC decreased markedly within 12 h after antigen challenge. Almost no recognization LCs could be seen within 2 to 5 days. Later, LCs began to repopulate in the epidermis. Within 14 days, the density and shape of the LCs returned to normal. On the contrary, LCs changed more rapidly in PICD. The dendritic processes of LC decreased within 2 h and cell density decreased dramatically within 6 h after DNCB application. LCs also repopulated more rapidly in the epidermis. Electron microscopically, in ACD, we observed that lymphocyte-like cells apposed to LCs; LCs were activated and damaged; however, in PICD, we found neither the apposition of lymphocyte-like cells to LCs, nor the activation of LCs. LCs play an important role in the convalescence phase as well as in the early and later phases of contact allergic reaction.     

紫外线、补骨脂素加长波紫外线、境界线对皮肤接触过敏的影响

DNCB致敏豚鼠.分成3组,于背部一侧剃毛后皮肤分别应用治疗剂量UVR,GR照射、PUVA疗法,每周2-3次.共调.然后,于照射处和对称部位的非照射处皮肤进行DNCB激发试验和切取皮肤作Laagerhans细胞检查.结果表明:3种物理因子均可抑制DNCB引起的皮肤接触过敏反应.与此同时,Langerhans细胞的数量亦明显减少,试验的结果进一步证明皮肤接触过敏的发病与Langerhans细胞密切有关.同时提示了UVR,PUPA和GR可用于接触性过敏性皮炎的治疗.     

Inhibition of cutaneous contact hypersensitivity by calcium transport inhibitors lanthanum and diltiazem

Epidermal Langerhans cells (ELC) are bone marrow-derived immune cells that are important in allergic contact dermatitis. We examined the influence of calcium transport inhibitors, lanthanum and diltiazem hydrochloride, on allergic contact dermatitis induced by 1-chloro-2,4-dinitrobenzene (DNCB) in BALB/c mice. Systemic lanthanum at a dose of 0.08 mg/kg and topical lanthanum (50 microliters of 10% solution) were given 5 d before DNCB sensitization. Systemic diltiazem (30 mg/kg per dy) was given for 3 d during sensitization with DNCB. In all animals, challenge with topical DNCB to the ear skin was performed 5 d after sensitization and ear swelling was measured. Twenty four hours post-DNCB challenge, animals receiving systemic lanthanum demonstrated a 56% decrease in contact hypersensitivity (ear swelling) compared with non-lanthanum-treated animals (0.08 +/- 0.03 mm vs 0.18 mm +/- 0.02 mm, p less than 0.01). Topical lanthanum produced a 58% decrease in contact hypersensitivity (0.20 +/- 0.02 mm vs 0.41 +/- 0.03 mm, p less than 0.01). The DNCB-induced ear swelling also resolved more quickly in animals treated with lanthanum. Systemic diltiazem produced a 67% decrease in ear swelling (0.05 +/- 0.01 mm vs 0.15 +/- 0.02 mm, p less than 0.001). A decrease in epidermal Langerhans cell density of 13 to 14% was produced by systemic lanthanum, detected by both ATPase staining and Ia staining, respectively (p less than 0.05). Approximately 20% of the Langerhans cells were morphologically abnormal, having become "rounded," and lacking normal dendritic processes. From these results, we infer that calcium transport across the cell membrane of ELC may be important in the regulation of their function. Lanthanides and other calcium-channel blockers may be useful pharmacologic agents to probe these phenomena.     

六种中药水煎剂抑制小鼠变应性接触性皮炎的研究

目的 探讨中药白鲜皮、金银花、当归、荆芥、生地黄、白芷抑制小鼠变应性接触性皮炎的效果及这六种中药的作用机制。方法 将小鼠按给药不同分为白鲜皮、金银花、当归、荆芥、生地黄、白芷、地塞米松（DXE）及生理盐水（NS）组,利用2,4-二硝基氟苯（DNFB）诱发的小鼠变应性接触性皮炎的动物模型,通过测量耳厚度差和耳重量差,及其对皮损中炎症细胞浸润、γ-干扰素（IFN-γ）、白细胞介素-10（IL-10）的影响,比较不同药物之间的疗效。结果 白鲜皮、金银花、当归、地塞米松组小鼠耳厚度及重量的增加、皮损中炎症细胞浸润数、小鼠血清IFN-γ水平均明显低于生理盐水组。结论 白鲜皮、金银花、当归具有明显抑制小鼠变应性接触性皮炎、减少IFN-γ分泌的作用。     

低浓度DNCB诱发豚鼠亚临床接触性皮炎的剂量效应关系

目的研究低浓度2,4-二硝基氯苯(DNCB)诱发豚鼠亚临床状态接触性皮炎的剂量-效应关系。方法以0.2000%,0.1000%,0.0500%、0.0250%和0.0125%五种浓度的DNCB溶液连续8周对豚鼠进行暴露,赋形剂作为对照,观察皮肤反应、评分。结果 0.0500%,0.1000%和0.2000%浓度组从第2周起相对于对照组出现有统计学意义的皮肤反应,皮肤反应强度随暴露次数的增多、暴露浓度的增高而增强;其中0.1000%和0.2000%浓度组出现评分>2分的皮肤反应,高于对照组(P<0.05),而0.0500%浓度组出现评分小于2分的亚临床状态皮肤反应,也高于对照组(P<0.05)。豚鼠皮肤反应强度与豚鼠暴露DNCB的累积剂量呈线性正相关(r=0.74,P<0.01)。结论低浓度DNCB可以诱发豚鼠亚临床接触性皮炎反应,反应强度随暴露浓度增高、暴露次数增多而增强;研究为变态反应型敏感性皮肤提供动物实验依据。     

2，4-二硝基氯苯诱导的特应性皮炎样小鼠模型的皮肤菌群特征研究

【摘要】 目的 探讨不同浓度2,4-二硝基氯苯（DNCB）诱导的特应性皮炎（AD）样小鼠模型特点及皮肤菌群改变。方法 将30只雄性、无特定病原级BALB/c小鼠按随机数字表法等分为3组：阴性对照组小鼠背部涂抹200 μl丙酮和橄榄油（体积比为3∶1）每周2次,连续6周;高、低浓度DNCB组小鼠于第1周的第1、3天均涂抹1% DNCB 200 μl,第2周起分别涂抹0.5%、0.1% DNCB 200 μl,每周2次,连续5周。末次给药24 h后评估皮损严重程度,测量经表皮水分丢失和角质层含水量。实验结束后处死小鼠,切取背部皮肤行组织病理学检查。每组取3只小鼠背部全层皮肤组织样本,通过Illumina Miseq PE300型高通量测序仪检测小鼠背部皮肤菌群16S rRNA基因V3-V4可变区,并分析皮肤菌群的组成结构及不同菌属相对丰度变化。采用单因素方差分析比较3组间各指标的差异,Games-Howell法进行两两多重比较。结果 高、低浓度DNCB组小鼠皮损严重程度评分分别为（9.83 ± 2.45）分、（2.71 ± 0.56）分,均显著高于阴性对照组［（0.51 ± 0.12）分］,t值分别为-7.19、-2.85,均P < 0.05。高、低浓度DNCB组经表皮水分丢失值均显著高于阴性对照组（t值分别为-7.72,-2.68,均P < 0.05）,而角质层含水量显著低于阴性对照组（t值分别为6.77、5.99,均P < 0.05）;高浓度DNCB组经表皮水分丢失值显著高于低浓度DNCB组（t = 2.76,P < 0.05）,而高、低浓度DNCB组间角质层含水量差异无统计学意义（P > 0.05）。3组间棒状杆菌属相对丰度差异有统计学意义（F = 249.85,P < 0.001）,高浓度DNCB组棒状杆菌属丰度显著升高。3组小鼠皮肤样本observed species和Chao1指数差异均无统计学意义（均P > 0.05）,而高浓度DNCB组Shannon指数显著低于阴性对照组和低浓度DNCB组（t值分别为6.96、-6.37,均P < 0.05）。结论 DNCB可诱导小鼠皮肤形成AD样皮炎,其皮损严重程度、屏障功能受损程度与DNCB浓度相关;高浓度DNCB组小鼠皮肤菌群物种多样性明显下降,高浓度DNCB造模对研究AD的微生物学变化更具优势。     

Down-regulation of Langerhans cell protein kinase C-β isoenzyme expression in inflammatory and hyperplastic dermatoses

The family of protein kinase C (PKC) isoenzymes plays a fundamental part in signal transduction, and thereby regulates important cellular functions, including growth, differentiation, cytokine production and adhesion molecule expression. In lesional psoriatic skin. Ca²⁺-dependent PKC activity, PKC-β protein and epidermal Langerhans cell (LC) PKC-β immunostaining are significantly decreased, indicating activation and subsequent down-regulation of PKC. Whether these changes occur in other inflammatory/hyperplastic dermatoses is, however, unknown. We examined PKC-α and PKC-β expression in normal skin, psoriasis, cutaneous T-cell lymphoma (CTCL), lamellar ichthyosis, non-bullous ichthyosiform erythroderma, atopic dermatitis, urushiol-induced allergic contact dermatitis, and sodium lauryl sulphate (SLS)-induced irritant contact dermatitis. Cryostat sections were stained for PKC-α and PKC-β, and the LC marker CDla, using an immunoperoxidase technique and specific monoclonal antibodies. Double-labelling studies, in normal skin, revealed co-expression of PKC-β and CDla by epidermal LCs. Analysis of the number of PKC-^β+ and CDl^a+ epidermal LCs, in diseased compared with normal skin, revealed three categories: (i) in psoriasis and CTCL. the PKC-^β+ epidermal LC number was significantly reduced, whereas the CDl^a+ epidermal LC number was unchanged; (ii) in allergic and irritant contact dermatitis, both PKC-β+ and CDla⁺ epidermal LCs were significantly reduced in number; and (iii) in atopic dermatitis, the PKC-β⁺ epidermal LC number was normal, and CDla⁺ epidermal LCs were significantly increased in number. Moreover, the ratio of epidermal LC PKC⁺/CDla⁺ was reduced in all the dermatoses studied, suggesting activation of PKC-β, with subsequent down-regulation. Within the dermis, increased PKC-β staining of infiltrating cells was observed in all the conditions studied except lamellar ichthyosis and non-bullous ichthyosiform erythroderma. These data indicate that: (i) down-regulation of LC FKC-β occurs in a variety of inflammatory and hyperplastic skin disorders, and is not unique to psoriasis, and (iii the pattern of epidermal LC PKC-β and CDla expression varies among the diseases studied. In mice, PKC activation induces LC migration. Thus, down-regulation of epidermal LC PKC-β associated with reduced CDla⁺ epidermal LCs in allergic and irritant contact dermatitis suggests that PK.C-β may transduce the signal for migration of LCs from human epidermis.