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(10g/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10d.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 ofdl-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.
