恩拉霉素对大鼠的慢性毒性试验

Chronic toxicity test of enramycin on rats

  • 摘要: 目的评估恩拉霉素对大鼠的慢性毒性作用,为其科学合理使用提供依据.方法选用240只SPF级Wistar大鼠为试验动物进行恩拉霉素的慢性毒性试验,根据其半数致死剂量(LD50)分别设高剂量组(1000 mg/kg)、中剂量组(200 mg/kg)、低剂量组(10 mg/kg)及空白对照组,按高、中、低剂量分别将恩拉霉素添加至大鼠饲料中加工成定制饲料,每天饲喂1次,连续饲喂6个月,通过临床观察、血液学分析、血清生化检测、脏器系数和病理学检查等评估恩拉霉素对大鼠的慢性毒性作用.结果在整个试验周期(6个月)内,各恩拉霉素剂量组的大鼠饮食饮水、大小便均正常,精神状况良好,被毛光泽,未出现死亡.与对照组相比,各恩拉霉素剂量组大鼠体重均无显著变化(P>0.05,下同);随着药物剂量的增加及给药时间的延长,恩拉霉素仅对大鼠中性粒细胞数有一定影响,对碱性磷酸酶、谷草转氨酶及白蛋白等血清生化指标有轻微影响.在脏器系数方面,连续给药6个月后,仅高剂量组大鼠肝脏和脾脏的脏器系数较对照组显著降低(P<0.05),其他的脏器系数均无显著变化.随着药物剂量的增加及给药时间的延长,恩拉霉素对大鼠的肝脏、肺脏、肾脏和心脏等器官组织会产生轻微影响,主要表现为:高剂量组大鼠肝脏组织中央静脉周围的细胞呈轻微肿胀;肺脏组织有一定程度的淤血,肺间质轻微增宽;肾脏组织轻微充血,且肾小管上皮细胞轻微肿胀;心肌纤维轻度萎缩,心肌间质增宽.结论恩拉霉素的毒性极低,随着药物剂量的增加及给药时间的延长,其对大鼠的慢性毒性作用非常轻微,即恩拉霉素的临床用药安全性极高.

     

    Abstract: ObjectiveThe study aimed to evaluate the chronic toxicity of enramycin on rats and provide scientific ba-sis for its rational use.MethodA total of 240 SPF-grade Wistar rats were selected to test the chronic toxicity of enramy-cin. High-dose group(1000 mg/kg),medium-dose group(200 mg/kg),low-dose group(10 mg/kg)and blank control group were divided according to enramycin half lethal dose(LD50). Enramycin was added to rat feedstuff in high,medium and low doses to be processed into customized feedstuff. The rats were fed once a day,continuously fed for six months. Then,the chronic toxicity of enramycin in rats was evaluated through clinical observations,hematology analysis,blood serum biochemical examination,organ coefficient and pathological examination.ResultDuring the entire test period(six months),rats in every treatment group were normal in drinking and urination,and were in good spirits with glossy coat, no rat was dead. Compared with the control group,there was no significant change in the body weight of each enramycin dose group(P>0.05,the same below). With the increase of drug dosage and prolongation of administration time,enramycinonly had certain effects on the number of neutrophils in rats,and it slightly affected blood serum indexes of alkaline phos-phatase,aspartate aminotransferase and albumin. In terms of organ coefficient,only six months after continuous medica-tion,the organ coefficients of liver and spleen only in high-dose group rats was significantly lower than that of the control group(P<0.05),and there was no significant change in other organ coefficients. With the increase of drug dose and pro-longation of administration time,enramycin slightly affected the liver,lung,kidney and heart of rats. The main manifes-tations were:in high-dose group,the cells around its central vein of liver tissue were slightly swollen;lung tissue had cer-tain degree of congestion,and the interstitial space was slightly widened;renal tissue was slightly congested,and renal tubular epithelial cells were slightly swollen;myocardial fibers were slightly atrophied,and myocardial interstitials were widened.ConclutionEnramycin has very low toxicity. With increase of drug dosage and prolongation of medication time,its chronic toxicity effects on rat is very slight,that is,the safety of enramycin in clinical medication is very high.

     

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