复方奥硝唑甲磺酸培氟沙星牙周缓释制剂对雄性大鼠的生殖毒性  

Reproductive toxicity of periodontal sustained release drug containing ornidazole and pefloxacin mesylate on SD male rats

作　　者：董正谋[1] 刘鲁川[1] 刘宁[1] 刘锐[1] 叶丽君[1] 李向杰[1] 敖琳[2] 

机构地区：[1]第三军医大学大坪医院野战外科研究所口腔科,重庆400042 [2]第三军医大学军事预防医学院卫生毒理学教研室,重庆400038

出　　处：《第三军医大学学报》2010年第22期2365-2369,共5页Journal of Third Military Medical University

基　　金：重庆市科技攻关计划项目(CSTC2009AC5019)~~

摘　　要：目的观察复方奥硝唑甲磺酸培氟沙星牙周缓释制剂对雄性大鼠的生殖毒性。方法 100只SD雄性大鼠采用随机数字表法分为阴性对照组,低、中、高剂量组和干预组,每组20只;低、中、高剂量组每日按体质量灌服复方奥硝唑甲磺酸培氟沙星牙周缓释制剂(1、4、8g/kg),阴性对照组按体质量灌服双蒸水,连续42d;干预组按体质量腹腔注射环磷酰胺(CP,40mg/kg),连续5d。给药期间观察一般情况、体质量变化,记录交配与生育情况,交配成功后处死,观察大体器官,计算睾丸、附睾系数,进行精子活动能力、计数和形态学观察,测定血清睾酮(T)、雌二醇(E2)水平,睾丸、附睾进行病理学检查,睾丸行细胞增殖核抗原(PCNA)、Bcl-2相关X蛋白(Bax)免疫组化分析。结果给药期间动物一般情况较好,干预组、高剂量组、阴性对照组在第2、3、4周时各死亡1只;高剂量组体质量(从第4周起)、睾丸及附睾系数、精子活动能力与计数、精子形态学与阴性对照组比较差异均有统计学意义(P<0.05);高剂量组T和高、中剂量组E2均降低,与阴性对照组比较差异均有统计学意义(P<0.05);常规病理检测结果示高剂量组出现生精上皮变薄,少数管腔细胞排列紊乱,间隙增大,输出小管、附睾管上皮明显变薄,细胞减少,管间疏松,间隙增大的现象;高剂量组免疫组化PCNA表达降低、Bax表达增多,与阴性对照组比较差异均有统计学意义(P<0.05)。结论高剂量的复方奥硝唑甲磺酸培氟沙星牙周缓释制剂对雄性大鼠生殖有一定的毒性作用;血清T、E2降低,PCNA表达减少与Bax表达增加可能是其生殖毒性的作用机制之一。Objective To explore the reproductive toxicity of a periodontal sustained release drug of compound ornidazole and pefloxacin mesylate on male rats. Methods A total of 100 male SD rats were randomly divided into negative control, low-, medium-and high-dose groups and intervention group by random digits table, with 20 animals in each group. The rats of low-, medium-and high-dose groups were fed daily with the the sustained release drug at 1, 4, and 8 g/kg respectively, and those of the negative group were fed daily distilled water, for continuously 42 d; and those of the intervention group were given cyclophosphamide （40 mg/kg） by intraperitoneal injection for continuously 5 d. During this period, general state and quality; mating and fertility, general organs, coefficient of testis and epididymis; sperm movement, count and morphology; serum T and E2 were determined respectively. Histopathological examination of testis and epididymis, and immunohistochemistry of testis for PCNA and Bcl-2 expressions were also respectively performed. Results The general state of these rats was good, except one was dead in the intervention group, high-dose and negative group respectively in 2, 3 and 4 weeks respectively. From the 4th week, the body weight, coefficient of testis and epididymis, and sperm mobility, counting and morphology in high-dose group were all statistically significant （P0.05）; pathological testis and epididymis in high-dose group were changed, T and E2 were also decreased, PCNA depressed, and Bcl-2 increased, with all these having significant difference with those of negative control （P0.05）. Conclusion There is certainly reproductive toxicity when our periodontal sustained release drug of compound ornidazole and pefloxacin mesylate is administered in a high dose for male rats. The mechanism underlying might be the reduced serum T and E2, decreased PCNA and increased Bax.

关 键 词：牙周缓释制剂 生殖毒性 精子 血清激素 免疫组化 

分 类 号：R944.9[医药卫生—药剂学] R965.3[医药卫生—药学]