dl-扁桃酸阴道热敏凝胶剂对小型猪阴道黏膜刺激性的研究

Study on Vaginal Irritation of dl-Mandelic Acid Thermosensitive in situ Gel in Miniature Pig

目的研究dl-扁桃酸阴道热敏凝胶剂对小型猪阴道黏膜的刺激性。方法将9只雌性小型猪按体质量随机分为空白胶组、讲．扁桃酸阴道热敏凝胶剂组和市售壬苯醇醚凝胶（N-9凝胶）组，肌肉注射苯甲酸雌二醇400μg／kg（促发情），12d后建立小型猪阴道刺激性试验模型，阴道给予5mL凝胶，每日一次，连续给药7d，在给药前和末次给药后的24h与72h，收集阴道灌流（CVL）液，流式细胞仪计数炎性细胞和中性粒细胞数目；末次给药72h后处死小型猪，取阴道组织，观察阴道黏膜组织病理学改变。结果dl-扁桃酸阴道热敏凝胶剂组CVL液中炎性细胞、中性粒细胞数目明显低于N-9凝胶组（P〈0．05）。小型猪阴道黏膜组织HE染色显示，dl-扁桃酸阴道热敏凝胶剂处理组阴道黏膜无明显上皮破损、血管充血以及炎症细胞浸润，其刺激性评分（5．10±0．47），与空白胶组（3．30±1．60）比较无显著性差异（P〉0．05），明显低于N-9凝胶组（20．50±3．50）（P〈0．05）。结论dl-扁桃酸阴道热敏凝胶剂对小型猪阴道黏膜刺激性较小。

Objective To study the vaginal irritation of dl-Mandelic acid thermosensitive in situ Gel （dl-Mandelic acid-TISG） in miniature pigs. Methods Nine miniature pigs injected with estradiol benzoate （400 μg/kg） were randomly divided into three groups： control group, dl-Mandelic acid -TISG group and nonoxynol-9 gel （N-9 gel） group. Each miniature pig was administrated with 5 mL gel through vagina once daily for 7 days. Cervicovaginal lavage （CVL） fluids were collected before administration and at the 24 h and 72 h after the last administration. The number of inflammatory cells and neutrophilic granulocytes in the CVL were detected by the flow cytometry. The miniature pigs were sacrificed at 72 h after the last administration. Histopathological changes of the vaginal mucosa were observed under light microscope. Results The number of inflammatory cells and neutrophilic granulocytes in the dl- Mandelic acid-TISG group were significantly lower than that in the N-9 group （P〈0.05）. Histological scoring of vaginal mucosa showed that there were no obvious mucosal epithelium damage, vascular congestion and inflammatory cell infiltration （5.10 ± 0.47） in the dl-Mandelic acid-TISG group.There was no significant difference （3.30 ± 1.60, P〉0.05） compared with the control group （P〉0.05） but significant difference compared with the N-9 group （20.50 ± 3.50, P〈0.05）. Conclusion The vaginal irritation of dl-Mandelic acid-TISG in miniature pigs is mild.