复方奥硝唑甲磺酸培氟沙星牙周缓释制剂对大鼠睾丸毒性的机制研究

摘要

目的：：观察复方奥硝唑甲磺酸培氟沙星( COPM)牙周缓释制剂对大鼠睾丸毒性的作用机制。方法：将40只SD雄性大鼠随机分为阴性对照组和低、中、高剂量组( n=10),每日分别按1、4、8 g/kg-1的剂量灌服COPM牙周缓释制剂,阴性对照组每日按体质量灌服相应体积的双蒸水,连续42 d。所有大鼠处死后,分别计算附睾系数,检查精子计数、活动率和畸形率；透射电镜观察生精细胞的超微结构；考马斯亮蓝法测定睾丸组织中乳酸脱氢酶( LDH)、碱性磷酸酶( ALP)、酸性磷酸酶( ACP )、γ-谷氨酰转肽酶(γ-GT)的活力；RT-PCR检测睾丸组织中雄激素结合蛋白( ABP)、抑制素-α( inhibin-α)基因的mRNA表达水平。结果：高剂量组睾丸、附睾系数减小,精子活力降低、计数减少、畸形率增加(P<0.05),生精细胞超微结构出现不同程度损害；高剂量组睾丸组织中的LDH、LAL、ACP和高、中剂量组的γ-GT活力降低；高剂量组睾丸组织中的ABP和inhibin-α mRNA表达水平下降(P<0.05)。结论：高剂量COPM牙周缓释制剂对大鼠睾丸有一定的毒性；睾丸组织中LDH、ALP、ACP、γ-GT的活力下降,ABP和inhibin-αmRNA的表达减少可能是其毒性作用机制之一。%AIM: To observe the testicular influence of compound ornidazole and pefloxacin mesylate ( COPM) of periodontal sustained release preparation on male rats and related mechanism. METHODS:40 male SD rats were divided into negative control, low, medium and high dose groups by random digit table(n=10) and were fed daily with COPM of the preparation at 1,4 and 8 g. kg-1 respectively, those in the negative group were fed daily by distilled water, continuously for 42 d. The coefficient of testis and epididymis, motility, count and deformity of sperm were exam-ined, ultrastructural examination on sperm atogenic cells were respectively observed;LDH, ALP, ACP,γ-GT in testicu-lar tissue were determined respectively, the mRNA expression of ABP and inhibin - α in testis was examtned. RESULTS:In high dose group the coefficient of testis and epididymis, motility, count and deformity of sperm were all decreased (P<0. 05);ultrastructure was changed; LDH, ALP, ACP, γ-GT, ABP and inhibin-α were all decreased (P<0. 05). CONCLUSION:COPM of periodontal sustained release preparations at high dose has toxicity on testis of male SD rats, the reduction of LDH, ALP, ACP,γ-GT, ABP and inhibin-αin testis may be the cause of mechanisms.