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ALA-Me光动力疗法诱导的免疫反应研究

Study on the Immune Responses Induced by ALA-Me Photodynamic Therapy
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摘要 目的探讨5-氨基乙酰丙酸甲酯盐酸盐(ALA-Me)介导的光动力疗法在黑色素瘤内诱导的抗肿瘤免疫反应。方法用人原代黑色素瘤细胞WM266-4建立36只Balb/c裸鼠无色素黑色素瘤模型。当黑色素瘤生长至大小为0.4×0.4 cm^(2)时,将36只裸鼠随机分为4组。ALA-Me静脉(IV)注射-PDT组、ALA-Me腹腔(IP)注射-PDT组、ALA-Me局部应用(EA)-PDT组和对照组不做任何处理。局部应用ALA-Me时,将浓度为25 mg/cm^(2)的乳膏涂抹于肿瘤组织上方。采用LED灯红光照射肿瘤部位,能量密度90 mW/cm2,能量密度50 J/cm^(2)。PDT后裸鼠体内肿瘤生长显著低于对照组裸鼠时将裸鼠脾脏细胞取出并经流式细胞仪进行测量。结果在经过ALA-MePDT处理的T细胞缺陷裸鼠脾脏中,观察到具有免疫调节功能的自然杀伤(NK)细胞数量显著上升。NK细胞在机体免疫系统中扮演着至关重要的角色,它们能够识别并消灭被病毒感染的细胞以及肿瘤细胞。同时,研究也发现B细胞的数量呈现下降趋势,这可能与NK细胞数量的增加相关,鉴于免疫系统中细胞间存在复杂的相互作用和调节机制。此发现不仅揭示了ALA-Me-PDT在免疫调节方面的新作用,还暗示了其可能具有促进对黑色素瘤免疫反应抑制的潜力。这为光动力学疗法在肿瘤治疗领域的进一步研究提供了重要的实验数据支持和理论基础,为未来的临床应用开辟了新的可能性。 Objective To investigate the antitumor immune responses induced by 5-aminolevulinic acid methyl ester hydrochloride(ALA-Me)mediated photodynamic therapy(PDT)in melanoma.Methods A non-pigmented mela-noma nude mouse model,which was challenged with human primary melanoma cells WM266-4,was established in 36 Balb/c nude mice.When the melanoma grew to a size of 0.4×0.4 cm^(2),the 36 nude mice were randomly divided in-to 4 groups,i.e.ALA-Me intravenous(IV)injection-PDT group,ALA-Me intraperitoneal(IP)injection-PDT group,ALA-Me external application(EA)-PDT group and a control group without any treatment.For topical application of ALA-Me,a cream with a concentration of 25 mg/cm^(2) was smeared on the top of tumor tissue.The tumor was irradiat-ed by an LED red light with an energy density of90 mW/cm2 and 50 J/cm^(2).After PDT,when the tumor growth in nude mice was significantly lower than that in the control group,the spleen cells of the nude mice were extracted and measured by flow cytometers.Results A significant increase in the number of immune natural killer(NK)cells with immunoregulatory functions was observed in the spleens of T-cell-deficient nude mice treated with ALA-Me-PDT.NK cells play a vital role in the immune system,which can recognize and eliminate virus-infected cells and tumor cells.At the same time,the number of B cells decreased,which may be correlated with the increase in NK cells,given the complex interactions and regulatory mechanisms among cells in the immune system.This finding not only reveals a novel role for ALA-Me-PDT in immune regulation,but also suggests its potential to promote the sup-pression of immune responses to melanoma.This provides important experimental data support and theoretical basis for further researches on photodynamic therapy in the field of tumor therapy,openning up new possibilities for fu-ture clinical applications.
作者 李安鑫 任婕 小普布卓玛 Li Anxin;Ren Jie;XiaoPubu Zhuoma(School of Ecological Environment,Xizang University,Lhasa 850000,China;School of Science,Xizang University,Lhasa 850000,China)
出处 《西藏科技》 2025年第4期17-25,共9页 Xizang Science And Technology
基金 国家自然科学基金项目(12164045)。
关键词 光动力疗法 黑色素瘤 免疫反应 NK细胞 B细胞 Photodynamic therapy Melanoma Immune response NK cells B cells
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