A novel gene therapy for radiation enteritis using HGF expressing plasmid chitosan complex

目的.放射性肠炎是许多恶性肿瘤放射治疗的主要副作用。本研究旨在探讨肝细胞生长因子（HGF）表达质粒壳聚糖复合物对放射性肠炎的保护作用。方法.产生HGF或LacZ表达质粒壳聚糖复合物。通过将表达HGF或LacZ的质粒壳聚糖复合物口服给药到C57 BL/6小鼠中进行基因转导。通过X-gal检测转导效率。用15戈伊全身照射法建立小肠放射损伤模型，TUNEL法检测小肠上皮细胞凋亡。通过组织学检查评估形态学分析。结果在上消化道粘膜中可实现有限和微弱的基因转导。HGF表达质粒壳聚糖复合物组在细胞凋亡和形态学分析方面均未表现出对放射性肠炎的保护作用。结论.本研究表明，表达HGF的质粒壳聚糖复合物对电离辐射所致的肠道损伤有一定的预防作用。

Purpose. Radiation enteritis is a major side effect of radiation treatment for many malignancies. This study investigated whether HGF (Hepatocyte Growth Factor) expressing plasmid chitosan complex would exert protective effects on the radiation enteritis. Methods. HGF or LacZ expressing plasmid chitosan complex were generated. Gene transduction was performed by oral administration of HGF or LacZ expressing plasmid chitosan complex into C57BL/6 mice. Transduction efficiency was examined by X-gal. Radiation-induced injury of the small intestine was induced by whole body irradiation (15 Gy) Apoptotic epithelial cells were visualized by TUNEL assay. Morphological analysis was assessed by histological examination. Results. A limited and weak gene transduction could be achieved in the upper gastro-intestinal mucosa. The HGF expressing plasmid chitosan complex group did not demonstrated the protective effects on the radiation enteritis in terms of both apoptotic and morphological analyses. Conclusions. This study indicates that HGF expressing plasmid chitosan complex has a powerless effect on preventing intestinal injuries caused by ionizing radiation.