dl-扁桃酸热敏凝胶对兔阴道黏膜炎症反应的研究  

Vaginal mucosa immune inflammatory response of dl-mandelic acid thermosensitive in situ gel in rabbits

作　　者：夏敏杰 王玉柱 田芳 杨明俊 杨威 丁训诚 李卫华 胡晶莹 Xia Minjie;Wang Yuzhu;Tian Fang;Yang Minjun;Yang Wei;Ding Xuncheng;Li Weihua;Hu Jingying(NHC Key Lab.of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research),Fudan University,Shanghai 200032,China;School of Public Health,Fudan University,Shanghai 200032,China)

机构地区：[1]复旦大学生殖与发育研究院上海市计划生育科学研究所,国家卫生健康委员会计划生育药具重点实验室,200032 [2]复旦大学公共卫生学院,上海200032

出　　处：《中华生殖与避孕杂志》2018年第11期898-904,共7页Chinese Journal of Reproduction and Contraception

基　　金：国家重点研发计划(2016YFC1000905)国家科技重大专项(2018ZX10301403-005-001);上海市卫生和计划生育委员会重点学科建设项目(15GWZK0201);上海市科委实验动物专项(1514091200);上海市科委生物医药科技支撑项目(18431900200);SIPPR攀登计划(PD2017-8).

摘　　要：目的探讨dl-扁桃酸热敏凝胶(dl-mandelic acid thermosensitive in situ gel,MA Gel)对兔阴道黏膜的刺激性及炎症反应情况。方法将40只雌兔随机分为基质对照组、MA Gel低剂量组(10 g/L)、MA Gel中剂量组(20 g/L)、MA Gel高剂量组(40 g/L)和市售壬苯醇醚凝胶(nonoxynol 9,N-9 Gel)组,每组8只,阴道给药2.5 mL,qd,连续10 d。在给药前、给药第4日以及末次给药后24 h与72 h,收集基质对照组、MA Gel高剂量组和N-9 Gel组阴道灌流(cervicovaginal lavage,CVL)液,流式细胞仪计数CVL中炎性细胞和中性粒细胞数目,并对CD45^+细胞进行分析。取阴道组织做组织病理切片,免疫组织化学检测阴道黏膜内CD45的表达。结果 MA Gel高剂量组CVL液中炎性细胞、中性粒细胞以及CD45^+细胞数目显著低于N-9 Gel组(P=0.036)。MA Gel各剂量组与基质对照组相比,阴道黏膜CD45^+表达无显著上升,主要表达在黏膜上皮层。结论 dl-扁桃酸热敏凝胶仅引起家兔阴道黏膜较轻微的炎症反应,未诱导局部炎性细胞的明显活化,安全性较好,具有研发成为阴道外用避孕药的前景。Objective To study the vaginal mucosal irritation and inflammatory response of dl-mandelic acid thermosensitive in situ gel (MA Gel) in rabbits.Methods Forty female rabbits were randomly divided into 5 groups: matrix control group, MA Gel low-dose group (10 g/L), MA Gel middle-dose group (20 g/L), MA Gel high-dose group (40 g/L), and nonoxynol 9 (N-9) Gel group. Gels were administered to rabbits through vagina at 2.5 mL once a day for 10 consecutive days. Cervicovaginal lavage (CVL) fluid of matrix control group, MA Gel high-dose group and N-9 Gel group was collected at 4 different time-points (before administation, 4th day of administration, 24 h and 72 h after last administration). The number of inflammatory cells, neutrophilic granulocytes, and CD45+ cells in CVL was detected by flow cytometry. The vaginal tissue was taken for histopathological slices and immunohistochemistry was used to detect CD45+ cells in vaginal mucosa.Results The number of inflammatory cells, neutrophilic granulocytes and CD45+ cells of MA Gel high dose group was significantly lower than that of N-9 Gel group (P=0.036). Compared with the matrix control group, the number of CD45+ cells in all MA Gel groups showed no significant increase, and the CD45+ cells mainly located in the vaginal epithelium.Conclusion MA Gel caused far lower vaginal mucosal irritation in rabbits than N-9 Gel, and it was not likely to induce significant local activation of inflammatory cells. Owing to its promising pharmaceutical effects and safety profile, MA Gel has the potential to be developed as a novel spermicide.

关 键 词：dl-扁桃酸 流式细胞术 阴道灌流液 炎症细胞 CD45 

分 类 号：R711.31[医药卫生—妇产科学]