疱疹灵药效学研究

目的 观察疱疹灵的镇痛、止痒和抗感染作用。方法 采用醋酸致小鼠扭体法及小鼠甲醛伤害法评价疱疹灵的镇痛作用及对痒痛反应的影响；以磷酸组胺悬滴刺激豚鼠破损后足背方法，观察本品的抗局部伤害作用；采用二甲苯致小鼠耳廓肿胀方法，探讨本品的消肿抗感染作用。结果 疱疹灵明显降低醋酸致小鼠扭体次数，减少小鼠因甲醛伤害舔咬后足及阴器的时间；本品明显降低所用磷酸组胺总量，提高豚鼠致痒阈；4倍于临床用量的疱疹灵还有一定的改善二甲苯致小鼠耳廓肿胀作用。结论 疱疹灵具有明显的镇痛、止痒作用，同时还具有一定的抗感染作用，皮肤局部用药后，有利千瘸疹件疾病疼痛、刺痒等痒状的改善．     

甘草酸软膏治疗豚鼠慢性湿疹模型的实验研究

目的 观察甘草酸软膏抗炎、止痒和对豚鼠慢性湿疹的治疗作用。方法 雄性昆明种小鼠、雌雄昆明种小鼠、白色豚鼠各60只,分别随机分为模型对照组（10只）、基质对照组（10只）、醋酸地塞米松乳膏组（10只）、甘草酸软膏高（10只）、中（10只）、低（10只）剂量组,各组分别建立二甲苯致小鼠耳廓肿胀模型,右旋糖酐40致小鼠搔抓模型,以及2,4-硝基氯苯反复刺激的慢性湿疹豚鼠模型,分别观察甘草酸软膏对小鼠耳廓肿胀和搔抓反应以及慢性湿疹豚鼠耳廓肿胀的影响。结果 甘草酸软膏高、中剂量可以抑制二甲苯致小鼠耳廓肿胀（P < 0.05或0.01）;甘草酸软膏高剂量可以延长右旋糖酐致小鼠搔抓的潜伏期,甘草酸软膏高、中、低剂量可减少搔抓次数（P < 0.05或0.01）,减轻慢性湿疹豚鼠模型耳廓的肿胀（P < 0.05或0.01）,并对耳廓皮肤的病理改变有一定的改善作用。结论 甘草酸软膏对慢性湿疹豚鼠模型有一定的治疗作用。     

甘草酸软膏治疗豚鼠慢性湿疹模型的实验研究北大核心CSCD

目的观察甘草酸软膏抗炎、止痒和对豚鼠慢性湿疹的治疗作用。方法雄性昆明种小鼠、雌雄昆明种小鼠、白色豚鼠各60只,分别随机分为模型对照组（10只）、基质对照组（10只）、醋酸地塞米松乳膏组（10只）、甘草酸软膏高（10只）、中（10只）、低（10只）剂量组,各组分别建立二甲苯致小鼠耳廓肿胀模型,右旋糖酐40致小鼠搔抓模型,以及2,4-硝基氯苯反复刺激的慢性湿疹豚鼠模型,分别观察甘草酸软膏对小鼠耳廓肿胀和搔抓反应以及慢性湿疹豚鼠耳廓肿胀的影响。结果甘草酸软膏高、中剂量可以抑制二甲苯致小鼠耳廓肿胀（P〈0．05或o．01）;甘草酸软膏高剂量可以延长右旋糖酐致小鼠搔抓的潜伏期,甘草酸软膏高、中、低剂量可减少搔抓次数（P〈0．05或0．01）,减轻慢性湿疹豚鼠模型耳廓的肿胀（P〈0．05或0．01）,并对耳廓皮肤的病理改变有一定的改善作用。结论甘草酸软膏对慢性湿疹豚鼠模型有一定的治疗作用。     

芩珠凉血合剂抗炎止痒作用的实验研究

目的研究中药芩珠凉血合剂对湿疹动物模型抗炎、止痒作用机制。方法①观察二甲苯引起小鼠耳廓肿胀，计算肿胀度、肿胀抑制率、病理变化，及芩珠凉血合剂抗炎作用。②观察磷酸组胺引起豚鼠背部创面瘙痒反应，计算豚鼠回头舔创面时磷酸组胺的总量，与芩珠凉血合剂止痒作用。结果发现芩珠凉血合剂具有抗炎作用；并能够提高磷酸组胺致痒阈。结论中药芩珠凉血合剂通过对抗炎症反应、提高磷酸组胺致痒阈影响，从而发挥对变态反应性疾病治疗作用。     

昆明山海棠与雷公藤急性毒性试验对比研究

目的:对比昆明山海棠与雷公藤乙醇提取液对小鼠的急性毒性.方法:灌胃给药后观察两药对小鼠的毒性反应、死亡时间、死亡率和脏器病理改变.结果:昆明山海棠和雷公藤乙醇提取液的LD50分别为34.84 g/kg和 16.31 g/kg.给予大剂量昆明山海棠(65.6 g/kg·d)和雷公藤(26.88 g/kg·d)后,肉眼见小鼠肝脏颜色变为灰白色,表面呈细颗粒状.光镜下肝细胞肿胀、胞浆内有大小不等的空泡以及数量不等的细胞凋亡.结论:昆明山海棠乙醇提取液的毒性小于雷公藤乙醇提取液.     

除湿止痒软膏抗炎及止痒作用研究

目的 探讨除湿止痒软膏的抗炎及止痒作用。 方法 用2,4-二硝基氟苯（DNFB）腹部致敏和背部反复激发建立BALB/c小鼠特应性皮炎模型。实验动物分为正常对照组（未致敏也未治疗）、模型对照组（致敏但未治疗）、氢化可的松乳膏组（致敏 + 氢化可的松）、除湿止痒软膏组（致敏 + 除湿止痒软膏）。连续用药14 d,末次给药12 h后取背部皮肤,测定皮肤厚度及质量,进行HE染色和甲苯胺蓝染色,ELISA法检测皮损组织中干扰素（IFN）γ、肿瘤坏死因子（TNF）α、白细胞介素（IL）-4、IL-5含量。利用磷酸组胺诱发Hartley豚鼠局部皮肤瘙痒模型,观察除湿止痒软膏对豚鼠致痒阈的影响。 结果 用药后第15天,与模型对照组相比,氢化可的松乳膏和除湿止痒软膏均可明显减少小鼠的背部皮肤厚度和质量（P < 0.01）,减少淋巴细胞和肥大细胞浸润（P < 0.01）以及降低皮损组织中IFN-γ、TNF-α、IL-4及IL-5水平（P < 0.05或P < 0.01）。与正常对照组相比,氢化可的松乳膏组小鼠背部皮肤厚度和质量减小（P < 0.01）,除湿止痒软膏组无明显变化。此外,除湿止痒软膏也可显著提高豚鼠耐受磷酸组胺的致痒阈（P < 0.01）。 结论 除湿止痒软膏可明显抑制DNFB引起的小鼠特应性皮炎,其抗炎机制可能与恢复体内Th1/Th2型细胞因子平衡有关。除湿止痒软膏可明显减轻磷酸组胺所致豚鼠皮肤瘙痒反应。     

昆明山海棠抗接触变应性光皮炎的研究

目的探讨昆明山海棠抗光变态反应的药效学和药理学。方法以氯丙嗪为光敏剂,在长波紫外线(UVA)的作用下建立起BALB/c小鼠的光变态反应动物模型,灌胃给药,测定小鼠耳部的肿胀程度差、重量差及真皮内浸润的单一核细胞数来判断各组药物的药效学;采用免疫组化测定小鼠皮损处角质形成细胞、成纤维细胞及血管内皮细胞的细胞间黏附分子1(ICAM-1)的表达,用酶联免疫吸附试验(ELISA)测定血清中干扰素-γ(INF-γ)水平,以阐明昆明山海棠的作用。结果昆明山海棠合剂组的左耳激发前后的厚度差、激发后左右耳的厚度差及组织块的重量差、局部浸润的单一核细胞均小于生理盐水对照(P<0.01),且小于昆明山海棠单剂组(P<0.05);昆明山海棠合剂组的皮损中ICAM-1和血清INF-γ明显低于生理盐水对照组(P<0.05)。结论昆明山海棠合剂组有显著的抗光变态反应作用,其作用比昆明山海棠单剂强,作用机制可能是抑制淋巴细胞INF-γ的分泌和表皮真皮内ICAM-1的表达,从而减少局部淋巴细胞的浸润,减轻变态反应。     

复方苦参止痒霜治疗湿疹的实验研究

目的研究复方苦参止痒霜治疗亚急性、慢性湿疹的作用机制.方法①观察复方苦参止痒霜对二甲苯致小鼠耳廓肿胀的影响;②观察复方苦参止痒霜对4-氨基吡啶(4-AP)1 mg/kg颈背部皮下注射诱发小鼠舔体反应是否有抑制作用;③采用二硝基氯苯(DNCB)将豚鼠先致敏后多次激发,建立右耳部亚急性接触性湿疹模型,随后观察复方苦参止痒霜与其中药提取液对实验模型是否有实验治疗作用.结果复方苦参止痒霜与其中药提取液对二甲苯致小鼠耳廓肿胀急性炎症没有明显的抑制作用;对4-AP所致小鼠皮肤瘙痒有显著的抑制作用;中药提取液组豚鼠的接触性湿疹较基质组明显好转,与丁酸氢化可的松组相近似.结论复方苦参止痒霜具有抗迟发型变态反应、止痒作用.     

刺山柑软膏抗炎止痒作用评价

目的：评价刺山柑软膏的抗炎、止痒作用。方法：昆明小鼠50只,随机分为基质组（10只）、丙酸氯倍他索组（10只）、刺山柑软膏组（低、中剂量各10只）,通过对二甲苯致鼠耳肿胀和冰醋酸致小鼠腹腔毛细血管通透性增高的影响评价刺山柑软膏抗炎作用,通过对右旋糖酐致小鼠全身瘙痒的影响评价刺山柑软膏止痒作用。结果：刺山柑乳膏可抑制鼠耳肿胀和腹腔毛细血管通透性增高．减轻小鼠全身瘙痒,且呈剂量依赖性。结论：刺山柑软膏具有抗炎、止痒作用。     

皮肤科学基础

972913 昆明山海棠对小鼠免疫功能的影响/刘如意…//西安医科大学学报。-1997,18（2）。-159～161 选用昆明山海棠乙醇提取物TH_590和TH_595对小鼠灌胃,以观察TH_590和TH_595对小鼠免疫功能的影响。通过碳粒廓清试验、血清溶血素测定及迟发超敏反应提示,上述两种昆明山海棠提取物对小鼠非特异性免疫、特异性体液免疫和细胞免疫功能均无明显抑制。表3参6（沈子伟）972914 三株B_（16）黑色素瘤细胞对NK细胞敏感性及细胞核DNA的测定/邵春奎…//上海第二医科大学学报。-1997,17（3）。-167～169     

复方酮康唑喷膜对豚鼠湿疹模型的实验研究

目的　观察复方酮康唑喷膜对豚鼠湿疹模型的疗效。方法　选择健康雌性豚鼠25只,每只背部剃毛4处,应用卵清蛋白(OVA)为抗原,激发豚鼠皮肤变态反应制备湿疹模型。将制备的模型随机分为A,B,C,D和E五组(N=100,n=20)。激发后给药,其中A,B,C组给予含高、中、低浓度地塞米松的复方酮康唑喷膜,D组给予地塞米松止痒霜,E组空白对照。根据形态学和组织病理学观察进行疗效评估。结果　豚鼠皮肤显示湿疹样皮损特点,组织病理呈湿疹样改变。药效学结果显示治疗1周时,A,B,C,D四组红斑、水肿评分和总分均明显降低(P<0. 05),而E组无明显变化。复方酮康唑喷膜与地塞米松止痒霜疗效一致,但给药次数明显减少。四组抑制率均在50%左右,B组抑制率最高,表明该组处方比较优化。结论　复方酮康唑喷膜能快速地抑制真皮炎症反应和变态反应性湿疹形成。     

复方利多卡因乳膏对小鼠接触性皮炎模型的治疗作用及免疫学机制探讨

目的观察复方利多卡因乳膏对接触性皮炎模型小鼠的治疗作用并探讨其免疫学机制。方法采用二硝基氯苯(DNCB)诱导小鼠接触性皮炎模型,均刺激4次。并将其随机分为模型对照组、复方利多卡因乳膏低、中及高剂量组[0.032,0.064,0.096g/(d·cm2)]和阳性药物[哈西奈德乳膏0.096g/(d·cm2)]对照组,每组12只;并另选择12只未致敏小鼠作为正常对照组。各用药组分别外涂药物于小鼠右耳的正和反两面,连用15d,正常对照组和模型对照组分别予空白基质外涂。用肉眼观察小鼠右耳结痂情况、测厚仪测量右耳中部厚度、电子天平称量左右耳片重量、ELISA法测定血清IL-2,IL-4,IL-12,IL-18及IFN-r水平。结果复方利多卡因乳膏低、中及高剂量组和哈西奈德乳膏组耳结痂发生率(41.67%、25.00%、8.33%和8.33%)、第4次激发后耳肿胀度(0.352±0.049,0.322±0.054,0.305±0.059和0.301±0.058)、左右耳重量差(5.678±3.642,3.092±1.937,2.106±1.034和14.731±2.857)均小于模型对照组(91.67%,0.404±0.077,8.642±2.369);另外,其血清IL-2、IL-12和IFN-r水平均高于模型对照组;血清IL-4和IL-18水平均低于模型对照组。以上均呈现良好的量-效依赖关系,差异均有统计学意义(P均<0.05)。结论复方利多卡因乳膏对接触性皮炎模型小鼠有良好的治疗作用,其治疗机制可能与调节血清Th1和Th2平衡有关。     

外用维拉帕米霜对豚鼠耳部皮肤的影响

将维拉帕米霜外涂于豚鼠耳部 ,观察其对豚鼠表皮的影响。结果发现 ,豚鼠耳部表皮变薄 ,郎格罕细胞分布未发生改变。提示外用维拉帕米治疗银屑病可能有效     

Anti pruritic effects of topical crotamiton, capsaicin, and a corticosteroid on pruritogen-induced scratching behavior

Itch accompanies various skin diseases. As a number of mediators other than histamine can be involved in the itch sensation, H1 receptor antagonists are not necessarily effective in treating itch. External application of antipruritic drugs is occasionally used as an alternative therapy for pruritic skin conditions, such as pruritus on primary non-diseased, non-inflamed skin. Even so, the actual effects of these drugs on the itch sensation have yet to be studied in detail. To verify the antipruritic effects of crotamiton, capsaicin, and a corticosteroid on the itch sensation, we examined the inhibitory effects of these drugs on various pruritogen-induced scratching behaviors in mice. Topical application of 10% crotamiton moderately inhibited histamine-, serotonin-, and PAR-2 agonist-induced scratching behaviors. Topical capsaicin (0.025%) also exerted a moderate suppressive effect on histamine-, substance P-, and PAR-2 agonist-induced itch responses. Notably, topical corticosteroid (0.05% clobetasol propionate) remarkably inhibited the scratching behaviors induced by all of the pruritogenic agents tested. Therapeutic effects of capsaicin on substance P-induced pruritus did not seem to be mediated by desensitization of the TRPV1 (+) C fibers and/or by altered responsiveness of the mast cells. In addition, the antipruritic effects of crotamiton and corticosteroid appear to be, at least partly, associated with a TRPV1-independent pathway. This study examined the itch responses to pruritogens and demonstrated the mode of action of the externally applied antipruritic drugs.     

Induction of eosinophil‐ and Th2‐attracting epidermal chemokines and cutaneous late‐phase reaction in tape‐stripped skin

Abstract: Skin barrier damage induces various harmful or even protective reactions in the skin, as represented by enhancement of keratinocyte cytokine production. To investigate whether acute removal of stratum corneum modulates the production of chemokines by epidermal cells, we treated ears of BALB/c and C57BL/6 mice by tape‐stripping, or acetone‐rubbing as a control of acute barrier disruption procedure. There was no difference between the tape‐stripped and acetone‐rubbed skin sites in the increased and recovered levels of transepidermal water loss. The mRNA expression levels of all the chemokines tested, including Th1 chemokines (CXCL10, CXCL9 and CXCL11), Th2 chemokines (CCL17 and CCL22) and eosinophil chemoattractant (CCL5), were higher in the epidermal cells from BALB/c than in those of C57BL/6 mice. In particular, CCL17, CCL22 and CCL5 were remarkably elevated in BALB/c mice and augmented by tape‐stripping more markedly than acetone‐rubbing, whereas Th1 chemokines were enhanced by acetone‐rubbing more remarkably. Tape‐stripping induced dermal infiltration of eosinophils in BALB/c but not C57BL/6 mice. In a contact hypersensitivity model, where BALB/c mice were sensitized on the abdomen and challenged on the ears with fluorescein isothiocyanate, mice exhibited higher ear swelling responses at the late‐phase as well as delayed‐type reactions, when challenged via the tape‐stripped skin. The challenge via tape‐stripped skin augmented the expression of IL‐4 and CCR4 in the skin homogenated samples, indicating infiltration of Th2 cells. These findings suggest that acute barrier removal induces the expression of Th2 and eosinophil chemokines by epidermal cells and easily evokes the late phase reaction upon challenge with antigen.     

Polidocanol inhibits cowhage ‐ but not histamine‐induced itch in humans

Polidocanol is a local anaesthetic and antipruritic compound that is used in the treatment of itching skin conditions such as eczema. Its mechanisms of action are largely ill defined. This study has compared the antipruritic efficacy of topical polidocanol in histamine‐induced itch and a histamine‐independent, cowhage‐induced model of pruritus. Polidocanol (3%) or vehicle was applied topically under occlusion for 1 h to the forearms of 45 healthy volunteers before itch was provoked by rubbing in 40–45 spicules of cowhage or skin prick testing with 10 mg/ml histamine. Itch was recorded at 1‐min intervals for 30 min on a 100‐mm visual analogue scale. Polidocanol significantly reduced the area under the curve for cowhage‐induced itch by 58% (P < 0.05), but had no significant effect on histamine‐induced itch. This result underlines the importance of histamine‐independent itch models in the development of topical antipruritic agents.     

An evaluation of the moisturizing and anti-itch effects of a lactic acid and pramoxine hydrochloride cream

An open-label, single-center, observer-blinded, controlled trial was conducted during the winter months to evaluate the moisturizing and antipruritic effects of a unique formulation of lactic acid 12% neutralized with ammonium hydroxide and pramoxine hydrochloride (HCl) 1% in 24 women with a history of dry itchy skin. Baseline assessments for appearance of dryness of both lower legs of each patient were conducted by a blinded expert grader; skin surface hydration was measured by the IBS Co, Ltd, Skicon-200 (Hamamatsu, Japan) conductivity meter; and dryness and itch were measured through self-assessment surveys. The women stopped the use of all moisturizing agents 7 days prior to and throughout the study and were allowed to use only a nonmoisturizing soap for bathing and shaving. Patients were randomized as to which leg to apply the test cream; the opposite leg was used as a nontreated control. Patients applied the test product liberally to the assigned leg twice daily for 7 days and had repeat assessments for appearance and hydration on the morning of days 3 and 7; self-assessments of itch and dryness were completed on days 1, 2, 3, 6, and 7. Expert grader assessment of skin dryness showed significant improvement with the test cream compared with no treatment on day 3 (P=.0004) and on day 7 (P<.001). Patients had statistically significant improvement in skin surface hydration by day 3 (P<.0001), with further improvement by day 7 (P<.0001). Patients also reported significant improvements in skin dryness and itch by day 1 (P<.0001 and (P<.0001, respectively), which continued to improve through day 7 (P<.0001 and P<.0001, respectively). In conclusion, the test cream was shown to be an effective moisturizer and antipruritic agent in treating dry itchy skin.     

虎榆软膏治疗变应性接触性皮炎小鼠模型的药效学及作用机制

目的:探讨虎榆软膏对变应性接触性皮炎(ACD)小鼠模型的疗效及抗炎机制.方法:用2,4-二硝基氟苯对C57小鼠腹部致敏,耳部和背部激发,分别建立急性ACD和慢性ACD模型.两种模型均随机分为5组:空白对照组、模型组、虎榆软膏组、阳性组、基质组.观察鼠耳组织病理学改变.急性ACD模型:比较各组耳厚度及左右耳质量差.慢性A...     

The hairless guinea-pig as a model for treatment of acute irritation in humans

BACKGROUND: The effect of six skin care formulations on experimentally induced acute irritation was studied in hairless guinea-pigs (HLGP) and in human volunteers (HV). The formulations were a basic cream, a carbomer cream and four modifications of the carbomer cream, containing either 10% isopropyl palmitate (IPP cream), 10% glycerol (glycerol cream), 19.5% canola oil (canola oil cream) or 0.5% (-)-alpha-bisabolol (bisabolol cream). METHODS: Acute irritation was induced by occlusive tests with 1% sodium lauryl sulfate aq. in both HLGP and HV, and in HV also by using nonanoic acid in n-propanol (NON) 20%. The irritant reactions were treated twice daily with the formulations from the time of removal of the patches. Evaluation of skin irritation and efficacy of treatments was performed daily for 4 days using clinical scoring, evaporimetry (transepidermal water loss), hydration measurement and colorimetry. RESULTS: The glycerol cream was the only product showing effects potentially better than no treatment in HV. CONCLUSION: The HLGP was too sensitive an animal model as a predictor for effect in humans. There was no difference in efficacy of the formulations against the two different irritants in HV.