钻原卟啉诱导血红素氧合酶-1表达对豚鼠银屑病样模型的影响

目的：确定钴原卟啉（CoPP）诱导血红素氧合酶-1（heme oxygenase-1,HO-1）对豚鼠银屑病样皮损的影响.方法：普萘洛尔外涂构建豚鼠的银屑病样模型,豚鼠腹腔内注射钴原卟啉（HO-1特异性诱导剂）或锌原卟啉（HO-1特异性抑制剂）,磷酸盐缓冲液（phosphate buffered saline, PBS）作为对照, 每周1次,共6周.记录皮损的动态评分和组织病理学评分.RT-PCR和Western-blot法检测动物耳部标本中的HO-1 mRNA和蛋白的表达.免疫组化染色方法检测标本中增殖细胞核抗原（proliferating cell nuclear antigen, PCNA）蛋白的表达和定位.结果：CoPP腹腔内注射显著诱导了HO-1 mRNA和蛋白的表达, CoPP治疗组银屑病样皮损的组织病理学评分和临床皮肤评分显著降低,与PBS对照组相比有显著性差异（P〈0.05）,同时CoPP治疗组的PCNA表达也显著低于PBS对照组（P〈0.05）.结论：钴原卟啉通过诱导血红素氧合酶-1的过表达对银屑病样皮损有治疗作用.     

血红素氧合酶-1对豚鼠银屑病样模型外周血中TNF-α和IL-10水平的影响

目的观察血红素氧合酶-1(heme oxygenase-1,HO-1)对银屑病豚鼠模型细胞因子IL-10和TNF-α的影响。方法通过外涂普萘洛尔在豚鼠耳部诱发银屑病样的皮损及病理变化,构建银屑病豚鼠模型。将模型鼠分为5组(n=10),在模型建立24h后,给予豚鼠腹腔内注射HO-1的特异性诱导剂-钴原卟啉(cobalt protoporphyrin, CoPP)来上调HO-1的表达, CoPP剂量分别为2. 5mg/kg, 5mg/kg, 10mg/kg和20mg/kg,并设0. 9%NaCl为对照组。观察银屑病样皮损的组织病理学变化,通过免疫组化染色和免疫印迹检测动物耳部标本中HO-1蛋白的表达和定位,采用ELISA法测定动物血清中IL-10和TNF-α的水平。结果普萘洛尔外涂诱发了动物银屑病样表现,腹腔内注射CoPP显著缓解了银屑病样的病理学变化,诱导了HO-1蛋白的表达,同时使动物血清中TNF-α的水平下降、IL-10水平上升,并与CoPP的剂量呈依赖性。结论 HO-1可以调节具有银屑病样皮损的动物体内细胞因子的分泌,这可能是其抗银屑病的机制之一。     

抗角蛋白自身抗体对豚鼠银屑病样模型的影响

目的：观察抗角蛋白自身抗体对（anti keratin autoantibody,AK auto Ab）对豚鼠银屑病样模型的作用。方法：应用心得安法制备豚鼠耳廓银屑病样模型，采用亲和层析法纯化的正常人AKatuoAb，以肌肉注射方式给药，从组织病理变化评价治疗效果。结果AKatuoAb组动物银现样改变的恢复程度明显优于对照组（P＜0．0001），动物血清中可检测人到AKatuoAb。结论：提示AKatuoAb具有促进及鼠银屑病样模型恢复的作用。     

基因工程抗角蛋白抗体对豚鼠银屑病样模型的影响

目的观察基因工程抗角蛋白抗体对豚鼠银屑病样模型的治疗作用及对角质形成细胞增殖的影响。方法建立豚鼠银屑病模型,将通过基因工程技术获得的抗角蛋白抗体Fab段以肌注方式给药,从组织病理水平评价抗体对豚鼠银屑病模型的治疗效果;将抗体与角质形成细胞共培养,MTT法观察其对角质形成细胞增殖能力的影响。结果抗角蛋白抗体Fab段可以促进豚鼠银屑病模型的恢复,抑制角质形成细胞的过度增殖。结论提示抗角蛋白基因工程抗体具有促进豚鼠银屑病样模型恢复的作用,对银屑病可能具有一定的治疗作用。     

置换肽对豚鼠银屑病样模型表皮增殖的治疗作用

目的观察置换肽(APL)对豚鼠银屑病样模型表皮增殖的治疗作用。方法采用心得安法制备豚鼠耳廓银屑病样模型,APL外涂给药,免疫组化法检测皮损中细胞增殖核抗原(PCNA)变化并评价疗效。结果APL组动物银屑病样改变的好转程度明显优于对照组(P<0.05)。结论提示APL具有促进豚鼠银屑病样模型康复的作用。     

置换肽对豚鼠银屑病样模型血清IFN-γ的抑制作用

目的探讨置换肽(APL)对豚鼠银屑病样模型血清IFN-γ浓度的影响。方法采用心得安法制备豚鼠耳廓银屑病样模型,APL组和对照组皮损处分别外涂APL及对照药物,ELISA法检测血清IFN-γ变化,分析涂药前、后各组内及组间的差异。结果APL组动物血清IFN-γ表达量明显低于对照组(P<0.05),高浓度的APL对IFN-γ的抑制作用更强。结论提示APL对豚鼠银屑病样模型血清IFN-γ的表达具有抑制作用。     

清热利湿饮对普萘洛尔致豚鼠银屑病样皮损的影响

目的:评价清热利湿饮对豚鼠耳部银屑病样病理改变的影响及安全性.方法:用心得安构建豚鼠耳部的银屑病样病理改变模型,喂饲不同浓度清热利湿饮,采用Baker法对组织学积分和真皮炎细胞浸润程度进行评分,以甲氨蝶呤(MTX)作为对照.结果:清热利湿饮组和MTX组Baker评分和炎症细胞浸润数显著低于模型组(P<0.01),而清热利湿饮组与MTX组比较差异无显著性(P>0.05).实验豚鼠各主要脏器未发现组织病理学改变.结论:清热利湿饮口服可改善豚鼠耳部银屑病样模型的病理变化,口服安全.     

青蒿琥酯外用对银屑病样小鼠模型的影响

目的研究青蒿琥酯外用对银屑病样小鼠模型的影响。方法采用鼠尾鳞片表皮鼠阴道上皮实验模型,观察青蒿琥酯溶液外用对鼠尾鳞片及阴道上皮细胞分裂的影响。结果1.5%青蒿琥酯溶液与乐肤液一样,具有显著抑制阴道上皮细胞有丝分裂,促进表皮颗粒层生成的作用。结论提示1.5%青蒿琥酯溶液外用可能可以治疗银屑病。     

中药新普连膏对银屑病样小鼠模型影响的研究

目的观察新普连膏外用对银屑病样小鼠模型的影响。方法新普连膏外涂小鼠尾部鳞片14d后,取鼠尾组织病理检查,设有安慰剂组及空白对照组。结果新普连膏对小鼠尾部鳞片表皮颗粒层形成的促进作用最为明显（F=235．83,P〈0．0001）。结论从动物模型的角度验证了新普连膏治疗银屑病有效。     

重组人甲状旁腺素（1-34）对银屑病样小鼠模型的影响

目的 研究重组人甲状旁腺素(1-34)对银屑病样小鼠模型的影响.方法 采用小鼠阴道上皮及鼠尾鳞片表皮实验模型,观察重组人甲状旁腺素(1-34)乳膏外用对鼠尾鳞片及阴道上皮细胞分裂的影响.结果 重组人甲状旁腺素(1-34)乳膏具有显著抑制阴道上皮细胞有丝分裂、促进表皮颗粒层生成的作用.结论 重组人甲状旁腺素(1-34)局部外用有望治疗银屑病.     

Sensitization and testing of guinea pigs with cobalt chloride

The guinea pig maximization test was used to study the sensitizing potential of cobalt chloride; 1 % CoCl2 was used for injection and 5 % for topical application. The animals were challenged twice; in series I epicutaneous testing was performed 3 weeks after sensitization and intradermal testing after yet another week. In series II the reverse schedule was used, i. e. intradermal testing after 3 weeks and epicutaneous after 4 weeks. CoCl2 was found to be a grade V allergen. The differences between cobalt-exposed and control animals (which had been treated with Freund's adjuvant, petroatum, occlusion, etc.) were statistically significant (P less than 0.001). however, the administration of cobalt at the first challenge testing caused this difference to diminish.     

ATPase and morphologic changes induced by UVB on Langerhans cells in guinea pigs

We have devised, in guinea pigs, an improved ATPase technique which enables one to proceed from light to electron microscope study while preserving, on the ultrastructural level, the various membranous structures, in particular the Langerhans cell (LC) granules. Using this method, we have been able to confirm the action of acute, low-dose UVB on the surface enzymatic marker, ATPase. Moreover, this study has shown that the ATPase-negative LC contain abnormal LC granules or, more often, are deficient in LC granules. In a previous work, we have shown that, after epicutaneous application of a hapten, one successively observes an extensive adsorptive pinocytosis process, the disappearance of the membranous ATPase system, and the appearance of LC granules in the cytoplasm. Therefore we may suppose that, after UVB irradiation, the disappearance of the ATPase system and/or the possible alteration of the adsorptive pinocytosis process interrupts or alters the formation of LC granules. These successive events might play a vital role in the formation of the hapten--carrier protein-Ia antigen complex. In their absence in a large number of LC, following UV irradiation, epicutaneous application of a hapten would lead to the development of a state of immune tolerance.     

Generalized rash induced by sulfhydryl drug in guinea pigs--a comparative study on it with cephalothin-induced rash in guinea pigs

Adverse reactions produced by sulfhydryl compounds with active thiol groups have generally formed a distinctive pattern in man when they are viewed as a class. It has been reported that cutaneous SH-induced drug eruptions have a wide variety of clinical presentations; histologically, they show a pattern of eosinophilic necrosis and/or satellite necrosis similar to that seen in cutaneous graft vs host reactions. In the present experiments, guinea pigs were sensitized with cephalothin (CET) and thiol compounds such as tiopronin (TP), D-penicillamine, gold sodium thiomalate or thiomalate, using a method similar to that described previously. In lymphocyte stimulation tests, lymph node cells from the sensitized animals responded positively to spleen cells pulsed with each thiol compound. Intracutaneous tests revealed some positive reactions to each thiol compound; there was a tendency to produce a tuberculin type reaction with indurated erythema rather than the Jones-Mote type seen in CET-induced reactions. The dose-requirements for positive intracutaneous tests and generalized rash (GR) due to thiol compounds were lower than for CET, which required relatively large doses. Histologically, infiltration of basophilic cells was prominent in the skin lesions induced by intracutaneous tests with CET and in those of CET-induced GR. On the other hand, intracutaneous tests with TP following the induction of TP-induced GR revealed eosinophilic degeneration of epidermal cells, which was similar to the eosinophilic necrosis seen in cutaneous GVHR. Intracutaneous tests after the induction of CET-GR did not show any eosinophilic changes in the epidermal cells. These findings are reminiscent of the characteristics of eruptions induced by thiol compounds in man, which differ from the eruptions induced by CET.     

银屑病动物模型研究进展

构建理想的银屑病动物模型是银屑病发病机制和开展药物治疗研究的关键,本文就银屑病模型的诱导,包括普萘洛尔诱导、咪喹莫特诱导、十二烷基硫酸钠诱导及细胞因子注射诱导和模型特点及局限性进行综述。