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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 observe the reproductive toxicity of compound ornidazole mesylate pefloxacin periodontal sustained release preparations in male rats. Methods 100 SD male rats were randomly divided into negative control group, low, medium and high dose groups and intervention group, with 20 rats in each group. The rats in low, medium and high dose groups were fed daily with body weight Nifedipine mesylate pefloxacin periodontal sustained-release preparations (1,4,8 g / kg), the negative control group according to the body weight of double distilled water, continuous 42d; intervention group according to the body weight of intraperitoneal injection of cyclophosphamide CP, 40 mg / kg) for 5 days. During the administration, we observed the general situation, the changes of the body weight, recorded the mating and reproduction, and killed them after the mating was successful. The general organs were observed, the testis and epididymal coefficient were calculated, the sperm motility, count and morphology were observed, The levels of E2, testis and epididymis were determined by immunohistochemistry. The expressions of proliferating cell nuclear antigen (PCNA) and Bcl-2 protein (Bax) were detected by immunohistochemistry. Results The animals were generally in good condition during the administration. One death occurred in each of the intervention group, the high dose group and the negative control group at the 2nd, 3rd, and 4th weeks. The body weight of the high dose group (from the 4th week), testis and epididymis There was significant difference between sperm motility and counting, spermatozoa morphology and negative control group (P <0.05), while high dose group (T) and high and middle dose group (E2) decreased, compared with the negative control group (P <0.05). The results of routine pathological examination showed that the thinning of seminiferous epithelium, the irregular arrangement of luminal cells and the increase of gap were observed in the high-dose group. The output tubules and epididymal tube epithelium were significantly thinner and the cells were reduced. Loose and gap increased. The expression of PCNA in high-dose group decreased and the expression of Bax increased. Compared with the negative control group, the difference was statistically significant (P <0.05). Conclusions High doses of compound ornidazole mesylate pefloxacin sustained-release periodontal preparations have some toxic effects on male rats’ reproductive performance. The serum levels of T and E2 decrease, the expression of PCNA and the expression of Bax may be their reproductive toxicity One of the mechanisms.