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血卟啉注射介导的胸部光动力疗法对小鼠Lewis肺癌播散性胸膜恶性肿瘤的疗效及机制

The efficacy and mechanism of thoracic photodynamic therapy mediated by hematoporphyrin injection on disseminated pleural malignancies of Lewis lung carcinoma in mice.

作者信息

Pu Wenjuan, Xue Lei, Han Ziqi, Yang Lei, Wang Yubao, Wan Nansheng, Feng Jing

机构信息

Department of Respiratory and Critical Care Medicine, General Hospital of Tianjin Medical University Tianjin 300052, China.

Department of Respiratory and Critical Care Medicine, Tangdu Hospital, Air Force Military Medical University Xi'an 710038, Shaanxi, China.

出版信息

Am J Cancer Res. 2022 Apr 15;12(4):1502-1510. eCollection 2022.

PMID:35530280
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9077060/
Abstract

In order to avoid the problems of long exposure time and high incidence of photosensitivity by intravenous injection of photosensitizer, our study explore the safety, efficacy, and possible mechanisms of photodynamic therapy (PDT) by intrathoracic administration of hematoporphyrin injection in the treatment of disseminated pleural malignancies of Lewis lung carcinoma in mice to provide a theoretical basis for thoracic PDT in the clinic. Hematoporphyrin was administered into the thoracic cavity of tumor-bearing mice, and the concentrations of hematoporphyrin in normal and tumor pleural tissues were detected by high-performance liquid chromatography. The tumor-bearing mice were randomly divided into four groups: model control, pure laser irradiation, PDT low-dose, and PDT high-dose groups. Hematoxylin and eosin (H&E) staining was used to observe the histological changes in normal pleural tissue. H&E and DNA in situ nick end-labeling staining were used to detect necrosis and apoptosis in the tumor tissues. The tumor volume in each group from high to low was as follows: model control group > pure laser irradiation group > PDT low-dose group > PDT high-dose group. Inflammatory cells infiltrated the normal pleural tissue of the PDT group. Necrosis was observed to different extents in the tumor tissues of the PDT group. The apoptosis index of each group from high to low was as follows: PDT high-dose group > PDT low-dose group > pure laser irradiation group > model control group. The differences were statistically significant (P<0.05). Hematoporphyrin selectively accumulated in tumor pleural tissues. PDT with intrathoracic administration of hematoporphyrin injection could inhibit the thoracic implant tumors in mice by inducing necrosis and apoptosis.

摘要

为避免静脉注射光敏剂时暴露时间长和光敏反应发生率高的问题,本研究探讨胸腔内注射血卟啉注射液的光动力疗法(PDT)治疗小鼠Lewis肺癌弥漫性胸膜恶性肿瘤的安全性、有效性及可能机制,为临床胸腔PDT提供理论依据。将血卟啉注入荷瘤小鼠胸腔,采用高效液相色谱法检测正常和肿瘤胸膜组织中血卟啉的浓度。将荷瘤小鼠随机分为四组:模型对照组、单纯激光照射组、PDT低剂量组和PDT高剂量组。采用苏木精-伊红(H&E)染色观察正常胸膜组织的组织学变化。采用H&E染色和DNA原位缺口末端标记染色检测肿瘤组织中的坏死和凋亡情况。各组肿瘤体积从大到小依次为:模型对照组>单纯激光照射组>PDT低剂量组>PDT高剂量组;PDT组正常胸膜组织有炎性细胞浸润;PDT组肿瘤组织均有不同程度坏死;各组凋亡指数从高到低依次为:PDT高剂量组>PDT低剂量组>单纯激光照射组>模型对照组,差异有统计学意义(P<0.05)。血卟啉能选择性地在肿瘤胸膜组织中蓄积,胸腔内注射血卟啉注射液的PDT可通过诱导坏死和凋亡抑制小鼠胸腔种植瘤。

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