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皮质类固醇对烧伤小鼠愈合的影响以及胃十五肽BPC - 157乳膏的作用

Corticosteroid-impairment of healing and gastric pentadecapeptide BPC-157 creams in burned mice.

作者信息

Sikiric P, Seiwerth S, Mise S, Staresinic M, Bedekovic V, Zarkovic N, Borovic S, Gjurasin M, Boban-Blagaic A, Batelja L, Rucman R, Anic T

机构信息

Department of Pharmacology Medical Faculty, University of Zagreb, Salta 11, PO Box 916, Zagreb 10000, Croatia.

出版信息

Burns. 2003 Jun;29(4):323-34. doi: 10.1016/s0305-4179(03)00004-4.

Abstract

The amelioration of corticosteroid-impairment of healing by a stable gastric pentadecapeptide BPC-157 (GEPPPGKPADDAGLV, M(w) 1419, currently in early clinical trials for inflammatory bowel disease) was studied in thermally injured mice. Its effects on corticosteroid impaired healing of deep partial skin thickness burns, and burn-gastric lesions were investigated. Male NMRI-Hannover mice (sacrificed at 1-3,7,14 and 21 days following burning 20% of total burn area at the back (open flame for 7s) received intraperitoneally (per kg bw) 6alpha-methylprednisolone (Depo-medrol, 1.0 or 10.0mg), or an equal volume of saline (5.0 ml), once daily, first application 30 min after injury, last 24h before sacrifice. The injury was subsequently treated by topical application of a thin layer of pentadecapeptide BPC-157 cream at three different levels a neutral cream of no treatment. Pentadecapeptide BPC-157 consistently improved given burn healing (both microscopical and tensionmetry assessment), and counteracted corticosteroid-impairment of burn healing. In burn-gastric lesions investigation of the effects of BPC showed an anti-ulcer effect of its own in burned non-corticosteroid-treated mice and potentiated the anti-ulcer effect observed in 6alpha-methylprednisolone-treated mice. Pentadecapeptide BPC-157 inhibited corticosteroid immunosuppression. In vitro, in spleenic cells assessment, animals (sacrificed at day 21) treated with 6alpha-methylprednisolone 1mg showed decreased reactivity to nitrogen in comparison with control, healthy animals, while the addition of BPC-157 (1 microg/g cream) returned cell reactivity to values noted in control healthy animals.

摘要

采用稳定的胃十五肽BPC-157(GEPPPGKPADDAGLV,分子量1419,目前正处于治疗炎症性肠病的早期临床试验阶段),对热损伤小鼠皮质类固醇愈合损伤改善情况进行了研究。研究了其对皮质类固醇损伤的深Ⅱ度皮肤烧伤愈合以及烧伤性胃损伤的影响。雄性NMRI-汉诺威小鼠(在背部20%的总面积烧伤后1、3、7、14和21天处死,采用明火7秒致伤),腹腔注射(每千克体重)6α-甲基泼尼松龙(德宝松,1.0或10.0毫克),或等体积的生理盐水(5.0毫升),每日一次,伤后30分钟首次给药,处死前24小时最后一次给药。随后,损伤部位分别用三种不同浓度的十五肽BPC-157乳膏、一种未治疗的中性乳膏局部涂抹处理。十五肽BPC-157持续改善烧伤愈合(显微镜和张力测定评估均显示),并抵消皮质类固醇对烧伤愈合的损伤作用。在烧伤性胃损伤研究中,BPC的作用表明,其在未用皮质类固醇治疗的烧伤小鼠中有自身抗溃疡作用,并且增强了在6α-甲基泼尼松龙治疗小鼠中观察到的抗溃疡作用。十五肽BPC-157抑制皮质类固醇免疫抑制作用。在体外脾细胞评估中,用1毫克6α-甲基泼尼松龙治疗的动物(在第21天处死)与对照健康动物相比,对氮的反应性降低,而添加BPC-157(1微克/克乳膏)后细胞反应性恢复到对照健康动物的水平。

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