局部应用氨磷汀对顺铂所致食管粘膜化学性损伤的保护作用

发布时间：2018-03-14 21:32

本文选题：DDP　切入点：食管癌　出处：《河北医科大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的:氨磷汀(Amifostine,AMI)是一种可选择性保护正常组织免受放化疗损伤的广谱细胞保护剂,但由于其全身用药毒副作用较大,限制了临床应用,探讨新的给药方式已成为当前的热门课题之一。本研究采用特制的食管局部给药装置,观察了食管局部应用氨磷汀对顺铂(Cisplstin,DDP)所致食管化学性损伤的保护作用,以期达到降低氨磷汀的副反应,增加患者耐受性的目的,为临床应用氨磷汀提供理论依据。方法:1给药方法麻醉成功后,将兔仰卧固定于工作台上,将自制食管局部给药装置经口腔插入食道,该装置由上、下球囊,骨架导管及管道等组成。用泛影葡胺造影剂将上、下球囊膨胀,这样,就在食管上、下球囊之间形成一个腔隙,然后向腔隙内灌注DDP和(或)氨磷汀药液。2食管腔内局部灌注化疗药对食管粘膜的影响36只大白兔随机分为3组,每组12只。对照组:食管局部灌注生理盐水,作用时间40min;0.25mg/ml DDP组:食管局部灌注0.25mg/ml DDP药液,作用时间40min;0.5mg/ml DDP组:食管局部灌注0.5mg/ml DDP药液,作用时间40min。观察各组动物食管局部灌注后6及14天食管组织学变化(每个时间点6只兔子)。3氨磷汀对DDP所致食管粘膜化学性损伤的保护作用24只新西兰大白兔随机分为四组:对照组、单纯氨磷汀组、单纯DDP组和氨磷汀+DDP联合组,每组6只。对照组:食管腔隙局部灌注生理盐水,作用40min;单纯DDP组:给药前食管腔隙局部先灌注生理盐水20min,然后吸出再灌注0.5mg/mL DDP药液,作用20min;单纯氨磷汀组:给药前食管腔隙局部先灌注生理盐水20 min,然后吸出再灌注0.2mg/mL氨磷汀药液,作用20min;联合组:给药前食管腔隙局部先灌注0.2mg/mL氨磷汀药液20min,然后吸出氨磷汀药液,再灌注0.5mg/mL DDP药液,作用20min。于给药后第6天处死兔子取标本行病理学检测。结果:1食管腔内局部灌注化疗药对食管粘膜的影响对照组兔食管灌注后不同时间,食管粘膜上皮正常。0.25mg/mlDDP组兔食管灌注后6及14天,食管粘膜上皮各层结构正常,仅见黏膜下层有炎细胞浸润,表皮角化层逐渐增厚;0.5mg/mlDDP组兔食管灌注后6天,食管粘膜上皮受损明显,并伴大片表皮脱落,粘膜下层及肌层有大量炎细胞浸润,之后受损食管黏膜上皮逐步恢复,14天食管粘膜上皮及各层结构基本正常。2氨磷汀对DDP所致化学食管粘膜损伤的保护作用肉眼观,对照组、氨磷汀组无明显变化,单纯DDP组灌注部位食管明显增粗、水肿,切开食管见粘膜表面有灰白色“伪膜”覆盖,粘膜糜烂。联合用药组灌注部位食管轻度增粗,无“伪膜”形成,粘膜表面光滑。光镜下,单纯DDP组食管粘膜层大部或全部脱落,粘膜下血管扩张充血,粘膜下层有大量炎细胞浸润,以中性粒细胞为主,深度达中肌层;联合用药组,食管粘膜上皮部分脱落,粘膜层有大量炎细胞浸润,粘膜下层及肌层见少到中度炎细胞浸润。实验动物的一般情况:24只兔子进食、水及精神可,于处理后第6天,兔子体重无明显下降。结论:1自制给药装置可实现食管腔内的局部给药,可为晚期食管癌提高一种姑息性的治疗手段。2食管癌腔内DDP浓度应控制在0.25-0.5mg/mL之间,浓度大于0.5mg/mL时,会对该部位食管粘膜上皮造成明显的可逆性损伤。3化疗前食管癌腔内局部给予氨磷汀可明显降低DDP所致食管粘膜的化学性损伤,可能为氨磷汀防治放射性食管炎提供了新的途径。
[Abstract]:Objective: amifostine (Amifostine, AMI) is a kind of selective protection of normal tissues from the broad-spectrum cytoprotective agent chemotherapy injury, but due to the systemic administration of toxic side effects, limiting the clinical application, explore the new mode of administration has become a hot topic of the current one. This research adopts special esophagus local drug delivery device, observe the esophageal topical application of amifostine on cisplatin (Cisplstin, DDP) protective effect caused by esophageal chemical injury, in order to reduce the side effects of amifostine, increase the tolerance of patients to use of amifostine to provide a theoretical basis for clinical medication. Methods: 1 after successful anesthesia, the rabbits were fixed on the table, will be made for local delivery of oral esophageal device inserted into the esophagus, the device is composed of a balloon catheter, and skeleton, piping and other components. With diatrizoate contrast agents, balloon expansion, such as. In esophageal, a lacuna formed by balloon, and then to the lacuna of infusion of DDP and (or) effect of amifostine liquid.2 esophageal cavity local infusion chemotherapy of esophageal mucosa of 36 rabbits were randomly divided into 3 groups, 12 rats in each group. The control group: local esophageal perfusion with normal saline, 40min time 0.25mg/ml; group DDP: 0.25mg/ml DDP esophageal perfusion liquid, reaction time 40min; group DDP: 0.5mg/ml 0.5mg/ml DDP esophageal perfusion liquid, reaction time 40min. to observe the change of 6 and 14 days of esophageal histology of each animal esophagus after local infusion (6 rabbits each time).3 protective effect of amifostine on DDP induced esophageal mucosal chemical damage of 24 New Zealand white rabbits were randomly divided into four groups: control group, simple amifostine group, DDP group and +DDP combined with amifostine group, 6 rats in each group. The control group: saline perfusion esophageal lacuna, 40min; D DP group: before administration of esophageal perfusion with normal saline 20min local lacuna first, then aspiration reperfusion 0.5mg/mL DDP liquid, 20min; simple amifostine group: before administration of esophageal Lacuna with 20 min of normal saline local first, then aspiration reperfusion 0.2mg/mL amifostine liquid, 20min; combination group: before drug the first local perfusion 0.2mg/mL esophageal cavity amifostine solution 20min, and then suck the amifostine liquid, reperfusion 0.5mg/mL DDP 20min. liquid, on the sixth day after administration, the rabbits were sacrificed and the specimens of pathological examination. Results: 1 esophageal cavity perfusion chemotherapy drug effects on esophageal mucosa in control group at different time esophageal perfusion in rabbits after the normal esophageal mucosa in group.0.25mg/mlDDP after 6 and 14 days of perfusion of esophagus, esophageal mucosal epithelial layers of normal structure, only submucosal infiltration of inflammatory cells, epidermal keratinization gradually thickening; 0.5mg /mlDDP group of rabbit esophageal perfusion After 6 days, esophageal mucosa was damaged, and with a large lower epidermis, and muscularis mucosa with infiltration of inflammatory cells, after injury of esophageal mucosa epithelium gradually restored, the protective effect of naked eye 14 days of esophageal mucosa and normal.2 structure of amifostine on esophageal mucosa injury caused by DDP chemical control concept. Group, amifostine group had no obvious change, simple esophageal DDP group perfused site obvious thickening, edema, and esophageal mucosal surface see gray pseudo membrane covering, mucosal erosion in combination group. Esophageal perfusion part of mild thickening, no pseudo membrane formation, the mucosal surface smooth. Under light microscope. Group of DDP esophageal mucosal layer most or all off, submucous hyperemia and submucosal infiltration of inflammatory cells, mainly neutrophils, depth of muscle layer; combination group, esophageal mucosa on the skin mucous layer is part of the loss, A large number of inflammatory cell infiltration, submucosa and muscular layer to see less moderate infiltration of inflammatory cells. The general situation of experimental animal: 24 rabbit food, water and the spirit, on the sixth day after treatment, the rabbit body weight did not decrease obviously. Conclusion: 1 homemade drug delivery device can realize the esophageal cavity local administration, for advanced esophageal cancer to improve a palliative treatment of esophageal cancer.2 cell DDP concentration should be controlled between 0.25-0.5mg/mL, the concentration is greater than 0.5mg/mL, will cause irreversible damage to.3 chemotherapy significantly before esophageal cancer cavity local administration of amifostine can significantly reduce the chemical damage caused by DDP on the site of the esophageal mucosa of esophageal mucosa, may provides a new way for Amifostine for prevention and treatment of radiation esophagitis.

【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R735.1

【参考文献】