5-氨基酮戊酸(ALA)是体表光动力疗法的一个重要前体药物, 通过代谢产物原卟啉Ⅸ(PpⅨ)介导发挥光敏作用。ALA制剂的研发和优化促生了一系列产品和技术, 不仅推动了体表光动力疗法的应用, 而且ALA介导的PpⅨ荧光还可用于肿瘤的荧光可视化和辅助手术。本文将对光动力诊疗中ALA及其酯类衍生物和PpⅨ的研究进展作一个系统介绍。

近年来,5-氨基酮戊酸(5-aminolevulinic acid, ALA)介导的光动力学疗法(photodynamic therapy, PDT) 已经广泛用于尖锐湿疣、人乳头瘤病毒(human papilloma virus, HPV)感染性皮肤病、非黑素瘤型皮肤癌及癌前病变、中重度痤疮、皮肤光老化等多种皮肤疾病, 并且取得良好疗效, 有安全性、低复发性、选择性、有效性、可重复性、灵活实用性、微创性等优点。ALA-PDT在光敏剂、光源的改进、优化治疗参数的促进下, 在皮肤科领域有很大的应用前景。现在将近年国内外ALA光动力学疗法在皮肤病中的研究及临床应用进展, 进行分析和总结, 为临床医生的合理使用及治疗的选择上提供依据。

Purpose: To evaluate the effectiveness of topical 5-aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) for the treatment of cutaneous lichen planus (LP). Methods: A total of 17 symptomatic LP lesions in 7 Chinese patients were assessed. ALA cream (10%) was applied topically to LP lesions for 3 h. The lesions were irradiated with a 635 nm diode laser at the dose level of 100 J/cm². The treatment was repeated at two-week intervals. Clinical assessment was conducted before each treatment. Follow-up was performed once a month for up to six months. Results: Lesions showed significant improvement after one to four courses of treatments. Complete response was achieved in 13 lesions (five patients) and partial remission in four lesions (two patients). The complete response rate was 71%. There was no significant side effects except the feeling of pain that most patients could tolerate. Follow-up of five patients who achieved complete response showed no signs of recurrence. Conclusion: Topical ALA PDT is effective in the treatment of cutaneous LP.

利用表面修饰的方法制备了5-ALA表面修饰的TiO2(5-ALA/TiO2), 并利用傅里叶红外光谱, 拉曼光谱以及紫外-可见光吸收光谱(UV-Vis)对样品进行了表征。利用 Cell Counting Kit-8 (CCK-8)法检测研究5-ALA/TiO2对HL60细胞的灭活效应。结果显示, 5-ALA/TiO2能够显著地抑制HL60细胞的生长, 5-ALA/TiO2对HL60细胞的灭活效率要明显高于5-ALA以及TiO2, 实验中5-ALA/TiO2的灭活效率达到77.9%, 相衬显微镜细胞形态学无损观察表明, 细胞凋亡开始于细胞膜的破裂。同时, 激光显微拉曼光谱检测显示, TiO2纳米粒子能够进入细胞内部, 与细胞发生相互作用。

Nasopharyngeal carcinoma (NPC) is a prevalent cancer in some areas of southern Asia. To explore the potential of photodynamic therapy (PDT) for the treatment of NPC, a small molecule prodrug 5-aminolevulinic acid (ALA) and its methyl ester (MAL) mediated PDT was studied in vitro. The results showed that human NPC cells were sensitive to both ALA- and MAL-mediated PDT. However, ALA was more effective than MAL, possiblly due to a higher efficiency of ALA on producing endogenous protoporphyrin (PpIX) in NPC cells. Neither ALA nor MAL caused any significant genotoxicity. The ALA-based PDT might be a useful modality in the treatment ofNPC.

To compare the efficacy and safety of CO₂ laser plus 5-aminolevulinic acid (ALA) photodynamic therapy (PDT) with CO₂ laser for the treatment of multiple condyloma acuminatum (CA), 120 patients with multiple CA were allocated into two groups — combined group (CO₂ laser plus ALA-PDT, n = 60) and CO₂ laser group (CO₂ laser plus placebo-PDT, n = 60). After CO₂ laser, a 20% ALA or a placebo solution was applied to the CA area 3 h before illumination with red light (635 nm, 100mW/cm2, 80 J/cm2T. The treatment was repeated seven days after the first treatment if the lesions were not completely resolved. The complete response rate, recurrence rate and adverse effects in the two groups were analyzed. After two treatments, the complete response rates in the CO₂ laser group and combined group were 100% (509/509) and 100% (507/507) in the CA (p > 0:05), respectively. The recurrence rates in the CO₂ laser group and combined group were 44.9% (229/509) and 10.6% (54/507) in the CA (p < 0:05), respectively. The adverse effects in CO₂ laser group was more than that in combined group. The combined group is a more effective treatment for multiple CA compared with CO₂ laser group. T/S. Style the highlighted text as abstract.

观察新型光敏剂5氨基乙酰丙酸（ALA）介导的光动力学疗法（PDT）治疗Fischer 344大鼠9L胶质瘤的效果并探讨其作用机制。20只雄性Fischer 344大鼠颅内种植9L脑胶质瘤细胞后，随机分为对照组、PDT治疗组（40 J/cm2组、80 J/cm2组和120 J/cm2组）。接种9L细胞7天后治疗组接受相应的ALA-PDT治疗。治疗后第7天处死所有动物，通过Hematoxylin-Eosin(H-E)染色法检测颅内肿瘤的生长情况；利用免疫组化法检测肿瘤细胞的增殖活性（Ki67）和TUNEL 法测定肿瘤细胞的凋亡。结果表明利用不同能量的ALA-PDT治疗后大鼠的生存状态明显改善，脑胶质瘤的体积减小，其治疗效果在一定范围内随着能量的增大而增强，但80 J/cm2和120 J/cm2的治疗效果基本相同。通过对肿瘤细胞增殖和凋亡的检测发现，ALA-PDT对细胞的增殖无影响，但可诱导肿瘤细胞的凋亡。ALA-PDT通过诱导肿瘤细胞的凋亡可有效治疗脑胶质瘤。

目的:研究5-氨基酮戊酸光动力疗法(ALA-PDT)治疗豚鼠耳背部寻常型银屑病模型的可行性和作用机制。方法:采用20%ALA溶液局部封包豚鼠耳背部银屑病模型皮损4h,再用635nm半导体激光照射,能量密度12J/cm2。分设模型对照组、单纯照光组、单纯ALA组、一次ALA-PDT治疗组、二次ALA-PDT治疗组,治疗后于第7d、14d、21d、28d进行组织病理学和增殖细胞核抗原免疫组化观察疗效。结果:ALA-PDT能够治愈豚鼠耳背部寻常型银屑病模型的病变;二次ALA-PDT治疗组疗效优于一次ALA-PDT治疗组;结论:ALA-PDT疗法能抑制豚鼠耳背部寻常型银屑病模型的表皮细胞异常增殖,并能消除局部组织炎性反应,其疗效与治疗次数正相关。

目的: 探讨5-氨基酮戊酸光动力疗法(5-Aminolevulinic acid - photodynamic therapy, ALA-PDT)治疗尿道尖锐湿疣的临床疗效,并对治疗后皮损的组织病理学变化进行研究.方法:对164例尿道尖锐湿疣患者进行了ALA-PDT治疗;并对11例外生殖器尖锐湿疣ALA-PDT治疗后的16个皮损进行了组织病理和超微研究. 结果:164例患者经ALA-PDT治疗后,156例疣体完全消失,治愈率高达95.12%,而复发率仅5.13%(8/156);无感染、溃疡、疤痕和尿道狭窄等副作用.治疗后1、3 h时表皮浅层角质形?上赴湫曰邓?5 h时表皮全层角质形成细胞坏死;电镜下发现治疗后1、3 h时线粒体一端肿胀、嵴断裂、内质网膜结构断裂、角质形成细胞变性和坏死、典型的细胞凋亡小体,5 h时大量角质形成细胞变性、坏死.结论:ALA-PDT是治疗尿道尖锐湿疣的简单、安全、有效、低复发率、耐受性好、无明显副作用的一种新疗法.ALA-PDT对尖锐湿疣的治疗作用是通过细胞凋亡和坏死两种途径实现的.