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α-(8-喹啉氧基)酞菁锌介导的光动力疗法治疗银屑病的效果及机制

Anti-Psoriasis Effects and Mechanisms of Α-(8-Quinolinoxy) Zinc Phthalocyanine-Mediated Photodynamic Therapy.

作者信息

Liu Han-Qing, Wang Ying-Ming, Li Wan-Fang, Li Chao, Jiang Zhi-Huan, Bao Jie, Wei Jin-Feng, Jin Hong-Tao, Wang Ai-Ping

机构信息

Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

Shenzhen Key Laboratory for Drug Addiction and Medication Safety, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Guangdong, China.

出版信息

Cell Physiol Biochem. 2017;44(1):200-214. doi: 10.1159/000484647. Epub 2017 Nov 9.

Abstract

BACKGROUND/AIMS: The aim of this study was to determine the anti-psoriasis effects of α-(8-quinolinoxy) zinc phthalocyanine (ZnPc-F7)-mediated photodynamic therapy (PDT) and to reveal its mechanisms.

METHODS

HaCaT cells were used to observe the influence of ZnPc-F7-PDT on cell proliferation in vitro. The in vivo anti-psoriasis effects of ZnPc-F7-PDT were evaluated using a mouse vagina model, a propranolol-induced cavy psoriasis model and an imiquimod (IMQ)-induced nude mouse psoriasis model. Flow cytometry was carried out to determine T lymphocyte levels. Western blotting was performed to determine protein expression, and a reverse transcription-polymerase chain reaction test was performed to determine mRNA expression.

RESULTS

The results showed that ZnPc-F7-PDT significantly inhibited the proliferation of HaCaT cells in vitro; when the light doses were fixed, changing the irradiation time or output power had little influence on the inhibition rate. ZnPc-F7-PDT significantly inhibited the hyperproliferation of mouse vaginal epithelium induced by diethylstilbestrol and improved propranolol- and IMQ-induced psoriasis-like symptoms. ZnPc-F7-PDT inhibited IMQ-induced splenomegaly and T lymphocyte abnormalities. ZnPc-F7-PDT did not appear to change T lymphocytes in the mouse vagina model. ZnPc-F7-PDT down-regulated the expression of proliferating cell nuclear antigen (PCNA), B-cell lymphoma-2 (Bcl-2), interleukin (IL)-17A mRNA and IL-17F mRNA, and up-regulated the expression of Bax.

CONCLUSION

In conclusion, ZnPc-F7-PDT exhibited therapeutic effects in psoriasis both in vitro and in vivo and is a potential approach in the treatment of psoriasis. Potential mechanisms of these effects included the inhibition of hyperproliferation; regulation of PCNA, Bcl-2, Bax, IL-17A mRNA and IL-17F mRNA expression; and immune regulation.

摘要

背景/目的:本研究旨在确定α-(8-喹啉氧基)锌酞菁(ZnPc-F7)介导的光动力疗法(PDT)的抗银屑病作用并揭示其机制。

方法

使用HaCaT细胞观察ZnPc-F7-PDT对体外细胞增殖的影响。使用小鼠阴道模型、普萘洛尔诱导的豚鼠银屑病模型和咪喹莫特(IMQ)诱导的裸鼠银屑病模型评估ZnPc-F7-PDT的体内抗银屑病作用。进行流式细胞术以确定T淋巴细胞水平。进行蛋白质印迹以确定蛋白质表达,并进行逆转录-聚合酶链反应试验以确定mRNA表达。

结果

结果表明,ZnPc-F7-PDT在体外显著抑制HaCaT细胞的增殖;当光剂量固定时,改变照射时间或输出功率对抑制率影响很小。ZnPc-F7-PDT显著抑制己烯雌酚诱导的小鼠阴道上皮细胞过度增殖,并改善普萘洛尔和IMQ诱导的银屑病样症状。ZnPc-F7-PDT抑制IMQ诱导的脾肿大和T淋巴细胞异常。ZnPc-F7-PDT在小鼠阴道模型中似乎未改变T淋巴细胞。ZnPc-F7-PDT下调增殖细胞核抗原(PCNA)、B细胞淋巴瘤-2(Bcl-2)、白细胞介素(IL)-17A mRNA和IL-17F mRNA的表达,并上调Bax的表达。

结论

总之,ZnPc-F7-PDT在体外和体内均对银屑病表现出治疗作用,是治疗银屑病的一种潜在方法。这些作用的潜在机制包括抑制过度增殖;调节PCNA、Bcl-2、Bax、IL-17A mRNA和IL-17F mRNA的表达;以及免疫调节。

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