摘要
目的 研究瘤体内注射不同浓度臭氧（O3）后兔VX2瘤组织超微结构的改变，以探讨臭氧用于实验研究/临床应用的安全有效浓度，并根据超微结构改变持续时间，推断重复治疗可能的间隔时间。方法 20只荷瘤大白兔分为4组，对照组2只，T20（20%臭氧）、T40（40%臭氧）和T60组（60%臭氧）治疗组各6只，直视下按瘤体积2倍量不同浓度的O2/O3混合气体用注射器直接注入瘤体内，对照组（仅模拟穿刺）及各治疗组取2只兔在实验完成后即刻取材，剩余兔分别于术后第4、8天各处死2只取材、制片，用透射电镜观察。结果 T20组注射臭氧后即刻可见肿瘤细胞有轻微的损伤改变，线粒体轻微嵴溶解，少许线粒体呈球状肿胀，内质网扩张，部分核周间隙增宽，细胞间隙正常。T40组和T60组注射臭氧后即刻均可见肿瘤细胞有明显损伤，表现为线粒体明显肿胀，内质网扩张，细胞核肿胀，核周间隙增宽，部分细胞膜崩裂，组织结构崩解，术后第4天，可见大片坏死，炎细胞浸润，肿瘤细胞膜不完整，溶酶体线粒体形成（呈新月形黑颗粒）或线粒体溶解，内质网扩张，部分胞质溶解，细胞核不规则，核周间隙扩张，T60组更明显。血管内皮细胞也有损伤改变。3组的细胞损伤在术后第8天仍可观察到，但呈逐渐修复状态。结论 兔VX2瘤内注射20% ～ 60%臭氧后，都会对肿瘤细胞、瘤内血管内皮细胞造成损伤甚至死亡，20%的损伤较轻微，40% ～ 60%的比较明显，但综合安全性及治疗效果， 40%臭氧可能更为明显。虽然有部分修复，但术后第8天仍可见较明确的细胞损伤改变，故治疗间隔以4 ～ 8 d为宜。
Objective To investigate the changes of uhra-microstructure of transplanted VX-2 tumor in rabbits caused by injeetion of different concentrations of ozone （03） into the tumor in order to determine the proper concentration of O3which ean be safely and effectively used in experimental study as well as in clinical practice, and based on the duration of the changes of uhra-microstructure to estimate the reasonable interval time for repeated injections of 03. Methods A total of 20 rabbits bearing VX-2 tumor on hind legs were randomly divided into four groups： control group （n = 2）, group T20 （n = 6, using 20% 03）, group T40（n = 6, using 40% 03） aml group T60 （n = 6, using 60% O3）. Under direct vision the mixed gas of O2 and O3 （20%, 40% or 60% O3 concentration） with twice the amount of tumor volume was injeeted into each study rabbit. Only imitation puncturing was performed in the two rabbits of control group. Ever7 two rabbits from each group were sacrificed immediately after the procedure, and the tumors were removed tor fixation. And evel7 two rabbits from the t＇emaining rabbits in each study group were sacrificed at 4 and 8 days after the procedure respectively. The specimens were collected, fixed, sectioned, and then sent for transnfission electron microscopic examination. Results In Group T20, mild injury of tumor cells was observed immediately after 03 injection, which was manifested as slight ridge lysis of mitoehondria and sporadic swelling of mitoehondria, dilation of endoplasmie retieulum, slight widening of peri-nuclear gap in some cells, but the intercellular space remained normal. In group T40 and group T60, obvious damage of tumor cells was observed immediately after O3 injection, which was characterized by pronounced swelling of mitoehondria, dilation of endoplasmic retieulum, swelling of nucleus, widening of peri-nuelear gap, a burst of cellular membrane and collapse of tissue structure in some tumor cells. On the 4th day, massive necrosis appeared with infiltration of inflammatory cells. Other changes included incomplete cellular membrane, mitoehondria-lysosome formation （presenting as black crescent particle of high electron-density） or lysis of mitoehondria, dilation of endoplasmic reticulum, partial lysis of cytoplasm, irregular nucleus and widening of peal-nuclear gap, etc., which were more significant and serious in group T60. Vascular endothelial cells appeared to be injured too. All these changes could be observed even on the 8th day after the treatment. The above mentioned changes could be gradually repaired. Conclusion After injection of 20% - 60% O3 into VX-2 tumor in rabbits, different degrees of damage or even death of the tumor cells and the vascular endothelial cells can be caused. The damage is slight when 20% O3 is used, while the damage is much remarkable when 40% or 60% O3 is employed. Taking both the safety and therapeutic effect into account the use of 40% O3 might be more suitable for both experimental and clinical use. The reasonable interval time for repeated injection of 03 should be 4 - 8 days as certain and definite cellular damage can still be observed at 8 days after the injection.（J Intervent Radiol, 2013, 22： 830-833）
出处
《介入放射学杂志》
CSCD
北大核心
2013年第10期830-833,共4页
Journal of Interventional Radiology
基金
国家自然基金资助项目(81071245)
作者简介
通信作者：杨继金、E-mail：jijinyang@sina.com
通信作者：熊源长、E-mail：jijinyang@sina.com
