Hawkins C W, Bickers D R, Mukhtar H, Elmets C A
J Invest Dermatol. 1986 Jun;86(6):638-42. doi: 10.1111/1523-1747.ep12275644.
Acute cutaneous photosensitivity is a major manifestation of certain forms of human porphyria and also occurs in patients treated with hematoporphyrin derivative (HpD) photoradiation for the diagnosis and treatment of malignant tumors. In this study a quantitative animal model useful for in vivo studies of acute porphyrin photosensitization in cutaneous tissue was developed. C3H mice injected with HpD and irradiated 6 h later with 405 nm energy developed a 40-90% increase in ear thickness which was present immediately after irradiation and persisted for at least 24 h. No ear swelling occurred in animals receiving 405 nm radiation alone or HpD alone. Histologically, this photosensitivity reaction was manifest as edema, vascular dilatation, and mast cell degranulation immediately after irradiation followed by an influx of polymorphonuclear leukocytes and epidermal necrosis 24 h later. Tissue injury evoked by HpD and light was accompanied by extravasation of intravenously administered 125I-labeled albumin in the irradiated ears, indicating that photosensitization was accompanied by transudation of serum into the site of tissue injury. An in vivo correlation of this approach was verified by detection of measurable increase in ear thickness in irradiated mice rendered porphyric by the ingestion of a griseofulvin-containing diet. The mouse ear swelling model offers a useful system with which to study acute porphyrin photosensitization in the skin, and may lead to important new insights into the pathogenesis and prevention of this form of phototoxicity.
急性皮肤光敏反应是某些类型人类卟啉病的主要表现，也见于接受血卟啉衍生物（HpD）光辐射以诊断和治疗恶性肿瘤的患者。在本研究中，建立了一种用于皮肤组织急性卟啉光敏化体内研究的定量动物模型。给C3H小鼠注射HpD，6小时后用405nm能量照射，耳部厚度增加40 - 90%，照射后立即出现并持续至少24小时。单独接受405nm辐射或单独接受HpD的动物未出现耳部肿胀。组织学上，这种光敏反应表现为照射后立即出现水肿、血管扩张和肥大细胞脱颗粒，随后24小时有多形核白细胞浸润和表皮坏死。HpD和光引起的组织损伤伴随着静脉注射的125I标记白蛋白在照射耳部的渗出，表明光敏化伴随着血清渗入组织损伤部位。通过检测摄入含灰黄霉素饮食致卟啉症的照射小鼠耳部厚度的可测量增加，验证了该方法在体内的相关性。小鼠耳部肿胀模型为研究皮肤急性卟啉光敏化提供了一个有用的系统，并可能为这种光毒性的发病机制和预防带来重要的新见解。
