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抗光敏合剂治疗日晒疮的临床疗效观察及对细胞凋亡影响的研究

【作者】 孙丽蕴

【导师】 杨博华; 王萍;

【作者基本信息】 北京中医药大学 , 中医外科学, 2010, 博士

【摘要】 光敏性皮肤病,中医称之为“日晒疮”,是由日光照射后在皮肤上引起多种病变的一组疾病,是皮肤科的常见、多发病。其机制与紫外线照射皮肤后诱导角质形成细胞凋亡,进而引起皮肤局部以及机体整个免疫系统的异常密切相关。论文主要包括文献综述和研究报告两部分。文献综述部分主要综述了日晒疮的中西医临床与基础研究概况,复习了中医经典对其病名的称谓,内外治方法及近年来的研究进展。研究报告分临床研究和实验研究两部分。目的:观察抗光敏合剂治疗日晒疮的临床疗效,及对急性UVB辐射后BALB/c小鼠皮肤细胞凋亡的影响,以探讨抗光敏合剂对皮肤光损伤的作用机理。方法:1.临床研究:通过随机、对照的临床研究,对治疗组(抗光敏合剂组)、阳性对照组患者各种疗效指标,包括皮疹颜色、形态及面积的变化,皮疹的瘙痒程度,伴随症状,安全性观察指标等的评定,比较二组的差异,并分析结果。2.实验研究:以300mJ/cm2 UVB辐射BALB/c小鼠建立急性光损伤的模型,在预防性应用中药抗光敏合剂后,与正常小鼠、预防性应用生理盐水及羟氯喹小鼠,进行平行对照研究。HE染色法观察炎症变化程度,TUNEL法检测细胞凋亡率,免疫组化法检测Fas、Caspase-3,荧光定量法检测TNF-α,进一步了解该药的作用机理。结果:1.临床研究结果显示:治疗组愈显率71.1%,总有效率91.1%;对照组愈显率45.4%,总有效率81.8%,治疗组的临床疗效优于对照组(P<0.05)。抗光敏合剂能有效地改善患者皮疹颜色,皮疹形态,皮疹面积,且在综合疗效、缓解靶皮损颜色和减少皮疹面积等方面均明显优于对照组。抗光敏合剂能有效改善患者心烦、口渴、小便黄赤等多项中医证候。抗光敏合剂安全可靠,适合临床应用。2.动物实验研究结果显示:中药抗光敏合剂可以抑制角质形成细胞经紫外线照射后出现的Caspase-3活性升高,下调Fas表达,从而抑制相应的信号传导,缓解急性UVB辐射损伤造成的细胞凋亡状态和细胞炎症反应,保护角质形成细胞,发挥对急性光损伤保护的作用机制。结论:抗光敏合剂治疗日晒疮疗效较好,安全性高;可明显缓解紫外线引起的表皮角质形成细胞炎性损害和细胞凋亡状态,其保护作用机理与调节细胞凋亡的Caspase-3通路及抑制Fas抗原水平密切相关。

【Abstract】 In this article, two parts are included. One is the literature review,and the other is study report.The author reviewed literature on photosensitivity research in traditional Chinese medicine in aspects of internal and topical treatment, laboratory research progress was also mentioned.Objective: 1. The aim of clinical research was to observe the effect of anti-photosensitivity mixture in treating polymorphous light eruption(PLE) and photoallergic contact (PACD).2. The aim of experimental research was to investigate the influence of anti-photosensitivity mixture to the apoptosis of epidermal cells of BALB/c mice irradiated by UVB.Methods:1.67 patients were divided into treatment group and positive control group. Pruritus, erythema, papule, blister, erosion, exudation, crust, accompany symptom, safty were measured after using the medcinces and the differences of improvement of symptoms and antipruritus were evaluated.2. BLAB/c mice were divided into treatment group, negative and positive control groups, and then irradiated with UVB in dosages of 300 mJ/cm2 for once. The apoptotic cells, immunohistochemistry of Fas and Caspase-3, immunofluorescence staining of TNF-αwere detected.Results:1.The total curative and effective rate of anti-photosensitivity mixture is 71.1%; the total curative and effective rate of control group is 45.47%, anti-photosensitivity mixture showed better effect with control group.2. At experimental research, anti-photosensitivity mixture showed simlar effects with positive control group.Conclusions:According to the result, anti-photosensitivity mixture showed that it could treat the photosensitivity effectively, with the mechanism of modulate keratinocyte apoptosis.

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