本文選題：DDP　切入點(diǎn)：食管癌　出處：《河北醫(yī)科大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：目的:氨磷汀(Amifostine,AMI)是一種可選擇性保護(hù)正常組織免受放化療損傷的廣譜細(xì)胞保護(hù)劑,但由于其全身用藥毒副作用較大,限制了臨床應(yīng)用,探討新的給藥方式已成為當(dāng)前的熱門課題之一。本研究采用特制的食管局部給藥裝置,觀察了食管局部應(yīng)用氨磷汀對(duì)順鉑(Cisplstin,DDP)所致食管化學(xué)性損傷的保護(hù)作用,以期達(dá)到降低氨磷汀的副反應(yīng),增加患者耐受性的目的,為臨床應(yīng)用氨磷汀提供理論依據(jù)。方法:1給藥方法麻醉成功后,將兔仰臥固定于工作臺(tái)上,將自制食管局部給藥裝置經(jīng)口腔插入食道,該裝置由上、下球囊,骨架導(dǎo)管及管道等組成。用泛影葡胺造影劑將上、下球囊膨脹,這樣,就在食管上、下球囊之間形成一個(gè)腔隙,然后向腔隙內(nèi)灌注DDP和(或)氨磷汀藥液。2食管腔內(nèi)局部灌注化療藥對(duì)食管粘膜的影響36只大白兔隨機(jī)分為3組,每組12只。對(duì)照組:食管局部灌注生理鹽水,作用時(shí)間40min;0.25mg/ml DDP組:食管局部灌注0.25mg/ml DDP藥液,作用時(shí)間40min;0.5mg/ml DDP組:食管局部灌注0.5mg/ml DDP藥液,作用時(shí)間40min。觀察各組動(dòng)物食管局部灌注后6及14天食管組織學(xué)變化(每個(gè)時(shí)間點(diǎn)6只兔子)。3氨磷汀對(duì)DDP所致食管粘膜化學(xué)性損傷的保護(hù)作用24只新西蘭大白兔隨機(jī)分為四組:對(duì)照組、單純氨磷汀組、單純DDP組和氨磷汀+DDP聯(lián)合組,每組6只。對(duì)照組:食管腔隙局部灌注生理鹽水,作用40min;單純DDP組:給藥前食管腔隙局部先灌注生理鹽水20min,然后吸出再灌注0.5mg/mL DDP藥液,作用20min;單純氨磷汀組:給藥前食管腔隙局部先灌注生理鹽水20 min,然后吸出再灌注0.2mg/mL氨磷汀藥液,作用20min;聯(lián)合組:給藥前食管腔隙局部先灌注0.2mg/mL氨磷汀藥液20min,然后吸出氨磷汀藥液,再灌注0.5mg/mL DDP藥液,作用20min。于給藥后第6天處死兔子取標(biāo)本行病理學(xué)檢測。結(jié)果:1食管腔內(nèi)局部灌注化療藥對(duì)食管粘膜的影響對(duì)照組兔食管灌注后不同時(shí)間,食管粘膜上皮正常。0.25mg/mlDDP組兔食管灌注后6及14天,食管粘膜上皮各層結(jié)構(gòu)正常,僅見黏膜下層有炎細(xì)胞浸潤,表皮角化層逐漸增厚;0.5mg/mlDDP組兔食管灌注后6天,食管粘膜上皮受損明顯,并伴大片表皮脫落,粘膜下層及肌層有大量炎細(xì)胞浸潤,之后受損食管黏膜上皮逐步恢復(fù),14天食管粘膜上皮及各層結(jié)構(gòu)基本正常。2氨磷汀對(duì)DDP所致化學(xué)食管粘膜損傷的保護(hù)作用肉眼觀,對(duì)照組、氨磷汀組無明顯變化,單純DDP組灌注部位食管明顯增粗、水腫,切開食管見粘膜表面有灰白色“偽膜”覆蓋,粘膜糜爛。聯(lián)合用藥組灌注部位食管輕度增粗,無“偽膜”形成,粘膜表面光滑。光鏡下,單純DDP組食管粘膜層大部或全部脫落,粘膜下血管擴(kuò)張充血,粘膜下層有大量炎細(xì)胞浸潤,以中性粒細(xì)胞為主,深度達(dá)中肌層;聯(lián)合用藥組,食管粘膜上皮部分脫落,粘膜層有大量炎細(xì)胞浸潤,粘膜下層及肌層見少到中度炎細(xì)胞浸潤。實(shí)驗(yàn)動(dòng)物的一般情況:24只兔子進(jìn)食、水及精神可,于處理后第6天,兔子體重?zé)o明顯下降。結(jié)論:1自制給藥裝置可實(shí)現(xiàn)食管腔內(nèi)的局部給藥,可為晚期食管癌提高一種姑息性的治療手段。2食管癌腔內(nèi)DDP濃度應(yīng)控制在0.25-0.5mg/mL之間,濃度大于0.5mg/mL時(shí),會(huì)對(duì)該部位食管粘膜上皮造成明顯的可逆性損傷。3化療前食管癌腔內(nèi)局部給予氨磷汀可明顯降低DDP所致食管粘膜的化學(xué)性損傷,可能為氨磷汀防治放射性食管炎提供了新的途徑。
[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.

【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R735.1

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