Lowering of sodium deoxycholate-induced nasal ciliotoxicity with cyclodextrins  

环糊精降低脱氧胆酸钠诱导的鼻纤毛毒性(英文)

作　　者：张奕[1] 蒋新国 姚洁 

机构地区：[1]复旦大学药学院药剂学研究室,上海中国200032

出　　处：《Acta Pharmacologica Sinica》2001年第11期1045-1050,共6页中国药理学报（英文版）

基　　金：Project supported by the National Natural Science Foundation of China,No 39770883

摘　　要：AIM: To lower the nasal ciliotoxicity of sodium deoxycholate (SDC) in combination with cyclodextrins (CD). METHODS: The erythrocyte hemolysis test was carried out to evaluate the damaging effect of SDC on the erythrocyte membrane. The in situ toad palate model and scanning electron microscope technique were used to investigate the nasal ciliotoxicity of SDC solution in combination with CD. The inclusion effect between SDC and β-cyclodextrin (β-CD) was studied by differential thermal analysis ( DTA ) and X-ray diffractometry. RESULTS: The hemolysis test showed that β-CD and dimethyl-β-cyclodextrin (DM-β-CD) could effectively protect the erythrocyte membrane against damage by SDC at the molar ratios of 1: 1 and 2: 1. When SDC combined with β-CD or DM-β-CD at a molar ratio of 1:2 or 1:3, the ciliotoxicity of SDC was greatly alleviated and the percent lasting time of the ciliary movement increased to 50 % or above. Scanning electron microscope investigations showed that SDC combined with 3-CD at a molar ratio 1; 2 had no marked damage on the rat nasal mucosa after nasal administration thrice a day for a week. DTA and X-ray diffractometry investigations showed that SDC formed an inclusion with β-CD. CONCLUSION: Combining β-CD or DM-β-CD with SDC can greatly lower the hemolytic effect and ciliotoxicity of SDC and the optimal molar ratio of SDC to CD is 1:2. Such protection provided by CD is due to the inclusion effect between SDC and CD.目的:用环糊精改善鼻腔吸收促进剂去氧胆酸钠(SDC)的鼻纤毛毒性。方法:分别用红细胞溶血实验、蟾蜍上腭模型和扫描电镜观察环糊精对SDC细胞膜破坏作用和鼻纤毛毒性的影响。SDC和β-环糊精(β-CD)之间的包合作用采用差示热分析法和X-衍射法进行验证。结果:当SDC与β-CD或二甲基-β-环糊精(DM-β-CD)的摩尔比为1:1和1:2时能完全掩盖SDC的溶血作用。用蟾蜍上腭模型评价时,加入摩尔比1:2或1:3的SDC与β-CD或DM-β-CD的混合液使SDC的相对纤毛持续运动时间由原来的0％提高至50％以上。大鼠鼻腔连续给予1:2摩尔比的SDC-β-CD溶液一周后,扫描电镜显示粘膜纤毛无明显改变。差示热分析法和X-衍射结果显示SDC能与β-CD形成包合物。结论:加入β-CD或DM-β-CD能显著降低SDC的溶血作用和鼻纤毛毒性,两者的最佳比例是SDC与环糊精摩尔比1:2。环糊精的这种保护作用与形成包合物有关。

关 键 词：deoxycholic acid cyclodextrins erythrocyte membrane nasal mucosa mucociliary clearance differential scanning calorimetry 

分 类 号：R94[医药卫生—药剂学]