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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(proliferatingcell 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。
Objective: To determine the effect of CoPP on heme oxygenase-1 (HO-1) induced guinea pig psoriasis-like lesions. Methods: Psoriasis-like model of guinea pig was constructed by topical application of propranolol. Guinea pigs were intraperitoneally injected with cobalt protoporphyrin (HO-1 specific inducer) or zinc protoporphyrin (specific inhibitor of HO-1) Saline buffer (phosphate buffered saline, PBS) as a control, once a week for a total of 6 weeks. The dynamic score and histopathological score of the lesions were recorded. The expression of HO-1 mRNA and protein in the ear of animals was detected by RT-PCR and Western-blot. Immunohistochemical staining was used to detect the expression and localization of proliferating cell nuclear antigen (PCNA). RESULTS: The intraperitoneal injection of CoPP significantly induced the expression of HO-1 mRNA and protein. The histopathological score and clinical skin score of psoriasis-like lesion in CoPP treatment group were significantly lower than those in PBS control group (P < P <0.05). Meanwhile, PCNA expression in CoPP treatment group was significantly lower than that in PBS control group (P <0.05). CONCLUSION: Cobalt protoporphyrin has a therapeutic effect on psoriatic lesions through the induction of heme oxygenase-1 overexpression.