防治放射性肠炎的口服龙油制剂研究

Oral Long oil for prevention and treatment of radiation enteritis

放射性肠炎(radiation enteritis,RE)是腹盆腔恶性肿瘤患者放疗常见并发症,严重影响生活质量,临床无专门防治药物。龙油(Long oil,LO)由海螵蛸、红花、核桃油、菜籽油中油脂成分组成,临床用于创伤修复。本研究将口服LO用于RE防治并探讨机制。所有动物实验经军事科学院军事医学研究院辐射医学研究所伦理委员会批准且实验均按照相关指导原则和规定进行。小鼠腹部经13 Gy的γ射线照射,成功建立RE模型。辐照前1 h给小鼠灌胃LO(8 mL·kg^(-1)),与模型组比较,辐照后第3.5日口服LO组小肠新生隐窝数量明显增多,小肠绒毛更长;第7日粪便肠道菌群丰度显著增加,特别是Eubacterium、Lactobacillus等益生菌的数量;第7日旷场实验显示口服LO组小鼠的运动总路程延长、不动时间变短、速度加快;第14日口服LO组小鼠的小肠组织中的促炎因子包括肿瘤坏死因子-α和白介素-6水平显著降低,接近正常水平。因此,口服LO可减轻RE症状,促进小肠损伤组织修复。荧光标记法证明口服LO组小鼠肠黏膜渗透性明显减小,达到正常水平。口服LO可通过改善肠道微环境、减轻炎症反应、促进组织修复等作用,保护肠黏膜,防治RE。

Radiation enteritis(RE)is a common syndrome in the radiotherapy of abdominal and pelvic malignant tumors,heavy influencing living quality,but no specific clinical regimens are available.Long oil(LO)is composed of the fat components from cuttlebone,safflower,walnut oil and rapeseed oil and has been clinically used for wound healing.In this study,oral LO was applied for the prevention and treatment of RE and the mechanisms were explored.Animal experiments were approved by the Ethics Committee of the Beijing Institute of Radiation Medicine,Academy of Military Medical Sciences,and the experiments were conducted in accordance with relevant guidelines and regulations.An RE mouse model was established after single whole abdominalγ-ray radiation of 13 Gy.LO(8 mL·kg^(-1))was intragastrically administered to the mice 1 h pre-radiation.Compared to the models,the mice of the LO group had more regenerated intestinal crypts and longer villus on day 3.5,and remarkable increase in the abundance of gut microbiota on day 7,especially the amounts of probiotics including Eubacterium and Lactobacillus.Moreover,the mice of the LO group showed longer total movement distance,shorter immobility time,and higher speed than the model mice on day 7.On day 14,the mice of the LO group showed the high descending of proinflammatory factors including tumor necrosis factor-αand interleukin-6,close to the normal levels.Therefore,oral LO can alleviate the inflamed syndromes of RE and improve the repair of damaged intestinal tissues.Moreover,the mice of the LO group had highly low permeability of intestinal mucosa according to the fluorescence labeling experiment,which was close to the normal level.Oral LO can protect intestine mucosa and prevent RE by modification of the intestinal microenvironment,alleviation of the inflammatory response,and promotion of tissue repair.