姜黄素温度敏感型原位凝胶治疗霉菌性阴道炎的研究  

Curcumin temperature-sensitive in situ hydrogels for treatment of vaginal candidiasis

作　　者：陈晓[1,2] 谌文元 麻培培 邱海莹 郝文艳 张丽花 金义光[2] 杜丽娜[1,2,3] 

机构地区：[1]山东中医药大学药学院,济南250355 [2]军事医学科学院放射与辐射医学研究所,北京100850 [3]潍坊医学院药学院,潍坊261053

出　　处：《国际药学研究杂志》2017年第10期947-952,共6页Journal of International Pharmaceutical Research

基　　金：国家自然科学基金应急管理项目(81441095)

摘　　要：目的考查姜黄素原位凝胶对霉菌性阴道炎的治疗效果。方法以泊洛沙姆188、407为基质,制备原位凝胶,测定其胶凝温度、胶凝时间及流变学性质。建立小鼠霉菌性阴道炎模型,分为正常组、模型组、阳性对照组(酮康唑乳膏)、0.025、0.10、0.20 g/ml姜黄素原位凝胶组。在第1次给药前、第4次及末次给药后,分别取小鼠阴道分泌物涂片、镜检;取阴道冲洗液测定乳酸杆菌DNA及白色念珠菌计数。末次给药后处死动物,取阴道组织进行病理检查。结果泊洛沙姆原位凝胶胶凝温度为29℃,胶凝时间为2′30″。流变学性质表明其体内滞留性良好。与模型组相比,姜黄素凝胶能明显抑制白色念珠菌生长、阴道黏膜水肿及炎性增生,且降低炎性因子TNF-α及IL-1β表达(P<0.01)。姜黄素原位凝胶不影响阴道内乳酸杆菌状态,说明其不通过调节乳酸杆菌发挥作用。结论姜黄素原位凝胶能抑制白色念珠菌生长、减轻阴道黏膜水肿、抑制炎性增生、降低炎性因子表达,为临床霉菌性阴道炎的治疗提供新选择。Objective To investigate the therapeutic effect of curcumin in situ hydrogels for treatment of vaginal candidiasis.Methods In situ hydrogels were prepared using poloxamer 407 and 188 as the gel matrix. Gelation temperature,gelation time and rheological characteristics were determined. Mice models with vaginal candidiasis were established. The animals were divided into six groups：the healthy mice group,the model group,the positive control group（ketoconazole cream）,curcumin-loaded in situ hydrogels of 0.025,0.10 and 0.20 g/ml. Before treatment and after the fourth and eighth treatments,the vaginal smears were collected and Gramstained. The vagina washings fluid of mice were collected to determine DNA of Lactobacillus. On 8 thday,the mice were sacrificed and the vaginal tissues were excised for pathological detection. Results The gelation temperature and time of in situ hydrogels were 29℃and 2′30″,respectively. Rheological profiles demonstrated that it showed good retention effect in vivo. Compared with the model group,curcumin hydrogels of 0.025,0.10 and 0.20 g/ml could inhibit the growth of Candida albicans,inhibit vaginal mucosal edema,inflammatory hyperplasia,and decrease the expression of inflammatory factors including TNF-α（P〈0.01）and IL-1β（P〈0.01）. However,curcumin hydrogels could not influence the growth of lactobacillus in the vagina. It indicated that curcumin hydrogels did not depend on lactobacillus to treat fungal vaginitis. Conclusion Curcumin in situ hydrogels could inhibit candidiasis growth,decrease edema of vaginal mucosa and inflammatory hyperplasia,and reduce the expression of inflammatory factors. It provides a novel choice for the treatment of clinical vaginal candidiasis.

关 键 词：姜黄素 原位凝胶 白色念珠菌 乳酸杆菌 霉菌性阴道炎 

分 类 号：R965[医药卫生—药理学]