丙酸氟替卡松对豚鼠鼻粘膜辐射性损伤的防护作用形态学观察及机制初探
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摘要
目的 (1)动态观察辐射及丙酸氟替卡松(fluticasone propionate，FP)应用后豚鼠鼻粘膜的组织病理学变化，(2)运用ELISA法检测辐射及应用FP后豚鼠血清IL-1、IL-6、TNF-α的含量变化，以初步探讨FP在鼻粘膜辐射性损伤中的防护作用机制。
方法 选用健康豚鼠100只，随机分为四组，即正常对照组(Ⅰ)，正常喷药组(Ⅱ)，单纯照射组(Ⅲ)，照射喷药组(Ⅳ)。每组25只，均在同样条件下喂养。照射组(Ⅲ、Ⅳ)照射剂量为5Gy，每周一次，共三次，总剂量15Gy。喷药用丙酸氟替卡松鼻喷雾剂(fluticasone propionate nasal spray，FPNS，商品名：辅舒良喷剂)，同时于照射结束后第二天开始喷豚鼠鼻腔，每天一次，喷双侧鼻腔，一侧一喷。分别于照射后1周、1月、2月、3月、4月处死动物各5只，在光镜及电镜下动态观察鼻黏膜的病理学变化，并进行图像学分析，动物处死前行心脏穿刺采血，离心后取血清，检测细胞因子IL-1、IL-6、TNF-α的含量变化。
结果 (1)正常喷药组 豚鼠鼻腔粘膜组织结构未出现异常变化，纤毛柱状上皮结构正常，无纤毛脱落，鼻腔粘膜完整，粘膜下腺体完整，功能正常。(2)单纯照射组 照射后鼻粘膜早期主要表现为急性炎症反应，鼻粘膜上皮变性明显，部分坏死脱落，粘膜下中性粒细胞及其它炎性细胞浸润，杯状细胞增多，分泌增强，粘膜下腺体排列紊乱。电镜下上皮细胞变性，有些区域上皮细胞缺失，残存上皮排列不齐，细胞连接间隙增宽，部分区域纤毛消失，胞膜部分溶解，胞质突出变形。扫描电镜下部分粘膜上皮脱落，纤毛倒伏、零乱，排列紊乱并失去正常形态结构，部分纤毛脱落。一个月后损伤上皮开始逐渐修复，但修复后大部分细胞失去正常纤毛柱状上皮形态，部分
Objective (1) To observe histopathologic changes of irradiated guinea pigs' nasal mucosa treated with fluticasone propionate (FP) , (2) To detect concentration of IL-1、IL-6 and TNF-α in serum of irradiated guinea pigs after using FP with ELISA and to study FP's radioprotective mechanism.
Methods 100 health guinea pigs were used and divided into 4 groups randomly: the control group(I),the administration group(II),the irradiated group(III) and the administration group after irradiation(IV), 25 guinea pigs for each group.the I and II group did not be irradiated,the III and IV group were performed irradiation by the WDVE-6MeV linear accelerator, giving 5Gy one time a week for three weeks through X-ray irradiating to establish the animal irradiation injury model.the II and IV group received fluticasone propionate nasal spray on the second day after three weeks irradiation, spraying double nasal cavities, one time every day and one spray each side. 5 animals per one group were sacrificed randomly at 1week, 1,2,3,4 month after irradiation, the histopathologic changes were observed under optical, scanning electron and transmission electron microscope. At the same time, blood were drawn from the heart and the concentration of IL-1,IL-6 and TNF-α in the serum were measured by ELISA.
Results (1) The administration group(II): The abnomal change did not be observed in the guinea pigs nasal mucosa received FP without irradiation. the nasal mucosa was integrity, the submucosa glandular organ was integrity and the function was normal. The ciliary cylindrical epithelium construction could not be found any damage and ciliary exfoliation. (2) The irradiated group(III): The early
方法 选用健康豚鼠100只，随机分为四组，即正常对照组(Ⅰ)，正常喷药组(Ⅱ)，单纯照射组(Ⅲ)，照射喷药组(Ⅳ)。每组25只，均在同样条件下喂养。照射组(Ⅲ、Ⅳ)照射剂量为5Gy，每周一次，共三次，总剂量15Gy。喷药用丙酸氟替卡松鼻喷雾剂(fluticasone propionate nasal spray，FPNS，商品名：辅舒良喷剂)，同时于照射结束后第二天开始喷豚鼠鼻腔，每天一次，喷双侧鼻腔，一侧一喷。分别于照射后1周、1月、2月、3月、4月处死动物各5只，在光镜及电镜下动态观察鼻黏膜的病理学变化，并进行图像学分析，动物处死前行心脏穿刺采血，离心后取血清，检测细胞因子IL-1、IL-6、TNF-α的含量变化。
结果 (1)正常喷药组 豚鼠鼻腔粘膜组织结构未出现异常变化，纤毛柱状上皮结构正常，无纤毛脱落，鼻腔粘膜完整，粘膜下腺体完整，功能正常。(2)单纯照射组 照射后鼻粘膜早期主要表现为急性炎症反应，鼻粘膜上皮变性明显，部分坏死脱落，粘膜下中性粒细胞及其它炎性细胞浸润，杯状细胞增多，分泌增强，粘膜下腺体排列紊乱。电镜下上皮细胞变性，有些区域上皮细胞缺失，残存上皮排列不齐，细胞连接间隙增宽，部分区域纤毛消失，胞膜部分溶解，胞质突出变形。扫描电镜下部分粘膜上皮脱落，纤毛倒伏、零乱，排列紊乱并失去正常形态结构，部分纤毛脱落。一个月后损伤上皮开始逐渐修复，但修复后大部分细胞失去正常纤毛柱状上皮形态，部分
Objective (1) To observe histopathologic changes of irradiated guinea pigs' nasal mucosa treated with fluticasone propionate (FP) , (2) To detect concentration of IL-1、IL-6 and TNF-α in serum of irradiated guinea pigs after using FP with ELISA and to study FP's radioprotective mechanism.
Methods 100 health guinea pigs were used and divided into 4 groups randomly: the control group(I),the administration group(II),the irradiated group(III) and the administration group after irradiation(IV), 25 guinea pigs for each group.the I and II group did not be irradiated,the III and IV group were performed irradiation by the WDVE-6MeV linear accelerator, giving 5Gy one time a week for three weeks through X-ray irradiating to establish the animal irradiation injury model.the II and IV group received fluticasone propionate nasal spray on the second day after three weeks irradiation, spraying double nasal cavities, one time every day and one spray each side. 5 animals per one group were sacrificed randomly at 1week, 1,2,3,4 month after irradiation, the histopathologic changes were observed under optical, scanning electron and transmission electron microscope. At the same time, blood were drawn from the heart and the concentration of IL-1,IL-6 and TNF-α in the serum were measured by ELISA.
Results (1) The administration group(II): The abnomal change did not be observed in the guinea pigs nasal mucosa received FP without irradiation. the nasal mucosa was integrity, the submucosa glandular organ was integrity and the function was normal. The ciliary cylindrical epithelium construction could not be found any damage and ciliary exfoliation. (2) The irradiated group(III): The early
引文
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41、 Salib, Rami Jean; Howarth, Peter Hugo Safety and Tolerability Profiles of Intranasal Antihistamines and Intranasal Corticosteroids in the Treatment of Allergic Rhinitis. Drug Safety. 2003,26(12):863-893.
2、R F Mould, MSc, PhD and T H P Tai, FRCR, FRCPC. Nasopharyngeal carcinoma: treatments and outcomes in the 20th century. British Journal of Radiology 75 (2002),307-339.
3、Mendelsohn, Felicia A. BA; Divino, Celia M. MD; Reis, Ernane D. MD; Kerstein, Morris D. MD, FACS. Wound Care After Radiation Therapy. Advances in Skin & Wound care .15(5):216-224 September/October 2002.
4、顾之燕．新一代鼻腔局部应用类固醇药物—丙酸氟替卡松和糠莫米松的临床研究．中华耳鼻咽喉科杂志，2002，37：472-477．
5、张学光，朱建昆．细胞因子与急性辐射损伤的防护和治疗．中华放射医学与防护杂志，2001，21(6)：397-400．
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