| 引用本文: | 陆珍,田芳,王玉柱,夏敏杰,孙冰,黄超,丁训诚,李卫华,陈华.采用优化家兔阴道刺激模型评价乙酸阴道热敏凝胶剂的阴道免疫炎症毒性研究[J].中国现代应用药学,2016,33(11):1372-1377. |
| LU Zhen,TIAN Fang,WANG Yuzhu,XIA Minjie,SUN Bing,HUANG Chao,DING Xuncheng,LI Weihua,CHEN Hua.Study on Using the Optimized Vaginal Irritation Model of the Rabbit to Evaluate the Vaginal Mucosal Immuno-inflammatory Toxicity of the Acetic Acid Vaginal Thermosensitive in Situ Gel[J].Chin J Mod Appl Pharm(中国现代应用药学),2016,33(11):1372-1377. |
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| 采用优化家兔阴道刺激模型评价乙酸阴道热敏凝胶剂的阴道免疫炎症毒性研究 |
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陆珍1, 田芳1, 王玉柱1, 夏敏杰1, 孙冰1,2, 黄超1, 丁训诚1, 李卫华1, 陈华3
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1.上海市计划生育科学研究所, 国家计划生育药具重点实验室, 上海 200032;2.复旦大学公共卫生学院, 上海 200032;3.复旦大学附属妇产科医院, 上海 200011
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| 摘要: |
| 目的 采用优化家兔阴道刺激模型评价乙酸阴道热敏凝胶剂（acetic acid vaginal thermosensitive in situ gel，Acid-TISG）对家兔阴道黏膜的免疫炎症毒性。方法 将24只♀家兔随机分为空白凝胶组、Acid-TISG组（12.11 mg·mL-1）、壬苯醇醚（nonoxynol-9，N-9）凝胶组（5.6 mg·mL-1），阴道给予3 mL凝胶，每天1次，连续10 d，给药前和给药后24 h收集家兔阴道灌洗液（cervicovaginal lavages，CVLs），检测CVL中白介素6（interleukin-6，IL-6）和肿瘤坏死因子α（tumor necrosis factor α，TNF-α）的含量。家兔处死后取阴道组织做病理学检查，HE染色观察家兔阴道黏膜组织损伤并进行评分。运用免疫组化技术检测阴道黏膜内白细胞共同抗原-CD45RB和核增殖抗原（proliferating cell nuclear antigen，PCNA）的表达。结果 与空白凝胶组相比，Acid-TISG组黏膜上皮完整，无明显炎症浸润、充血和水肿，N-9凝胶组黏膜上皮出现脱落，固有层炎性细胞明显增多（P<0.05）；空白凝胶组和Acid-TISG组阴道黏膜无明显CD45RB阳性表达，N-9凝胶组阴道黏膜固有层出现较多的CD45RB阳性表达细胞。与空白凝胶组相比，Acid-TISG组的阴道黏膜PCNA表达增多，但无显著性差异，N-9凝胶组的阴道黏膜PCNA阳性表达细胞明显增多（P<0.05）。与给药前相比，给药后24 h时CVL中IL-6和TNF-α含量在空白凝胶组和Acid-TISG组无明显改变，N-9凝胶组明显升高（P<0.05）。结论 Acid-TISG对家兔阴道黏膜无明显免疫炎症毒性，优化的家兔阴道刺激模型可用来评价生殖道外用药物对阴道黏膜的免疫炎症毒性。 |
| 关键词: 乙酸 热敏凝胶 阴道黏膜 免疫炎症毒性 CD45RB PCNA |
| DOI：10.13748/j.cnki.issn1007-7693.2016.11.005 |
| 分类号:R965.3 |
| 基金项目:上海市科委项目（13431900801，1514091200）；上海市环境卫生和劳动卫生学重点学科建设项目（15GWZK0201）；国家科技部中青年科技创新领军人才项目（万人计划） |
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| Study on Using the Optimized Vaginal Irritation Model of the Rabbit to Evaluate the Vaginal Mucosal Immuno-inflammatory Toxicity of the Acetic Acid Vaginal Thermosensitive in Situ Gel |
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LU Zhen1, TIAN Fang1, WANG Yuzhu1, XIA Minjie1, SUN Bing1,2, HUANG Chao1, DING Xuncheng1, LI Weihua1, CHEN Hua3
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1.State Key Labs of Family Planning Devices, Shanghai Institute of Planned Parenthood Research, Shanghai 200032 China;2.School of Public Health, Fudan University, Shanghai 200032, China;3.Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China
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| Abstract: |
| OBJECTIVE To evaluate the immuno-inflammatory toxicity of vaginal mucosa of acetic acid vaginal thermosensitive in situ gel(Acid-TISG) by using the optimized vaginal irritation model in the rabbits. METHODS Twenty-four rabbits were divided randomly into the blank gel group, Acid-TISG group (12.11 mg·mL-1) and positive nonoxynol-9 (N-9) group (5.6 mg·mL-1). Gel was administered through vagina to rabbits at 3 mL per day for 10 d. Cervicovaginal lavages (CVLs) were collected at pre-administration and 24 h after the last administration. The concentrations of interleukin-6 (IL-6) and tumor necrosis factor-α(TNF-α) in the CVLs were detected. The pathological examination of the vaginal tissues was conducted, and the vaginal irritation was assessed and scored. The expression of leukocyte common antigen-CD45RB and proliferating cell nuclear antigen (PCNA) in the vaginal mucosa was detected by the immuno-histochemistry (IHC) assay. RESULTS The vaginal mucosal epithelium in the rabbits of the Acid-TISG group was intact with no obvious inflammation infiltration, congestion and edema; while the exfoliation of mucosal epithelium cells and the increase of the inflammatory cells were obviously observed in N-9 gel group(P<0.05). There was no obvious positive expression of CD45RB cells both in the blank gel group and the Acid-TISG group, but the positive expression of CD45RB cells increased significantly in the N-9 gel group(P<0.05). The concentrations of IL-6 and TNF-α in CVLs, were significantly increased in the N-9 gel group(P<0.05) 24 h after administration while there were no significantly increase in both blank gel group and the Acid-TISG group compared with predose. CONCLUSION Acid-TISG is unlikely to cause vaginal mucosal irritation in the rabbits. The optimized rabbit vaginal irritation model can be used to evaluate the topical toxicity of the candidate vaginal drugs. |
| Key words: acetic acid thermosensitive in situ gel vaginal mucosa immuno-inflammatory toxicity CD45RB PCNA |
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