摘要
目的分析不同剂型以及负荷剂量西罗莫司对大鼠生存效益和毒性作用的影响。方法选取雄性SD大鼠60只,随机分为A1组(片剂普通灌胃)、A2组(片剂缓释灌胃)、A3组(片剂缓释灌胃)、B1组(口服液普通灌胃)、B2组(口服液缓释灌胃)、B3组(口服液缓释灌胃),每组10只;A1、A2、B1、B2组负荷剂量为1 mg/kg,1/d;A3、B3组负荷剂量为0.5 mg/kg,1/d;实验持续30 d。观察6组大鼠的生存效益及毒性作用,包括饮食情况、体重、器官病变、死亡率和存活时间。结果第30天,A1、A2、A3组间体重比较差异具有统计学意义(P<0.01);B1、B2、B3组间体重比较差异具有统计学意义(P<0.01)。A1组死亡率显著高于A2组(P=0.025),A2组死亡率高于A3组(P=0.019)。B1组死亡率显著高于B2组(P=0.025),但B2组与B3组比较差异无统计学意义(P=0.06)。低负荷剂量组具有良好生存效益,生存时间显著延长,组间差异有统计学意义(P<0.01)。与高负荷剂量组相比,低负荷剂量组大鼠肝、肺、胃脏器的病变数目少,病变程度轻。结论低负荷剂量(0.5 mg/kg)缓释SRL干预可显著降低实验大鼠的死亡率、延长生存时间,毒性作用小,生存效益良好。
Objective To analyze effects of different dosage forms and loading doses of Sirolimus on survival efficiency and toxicity of rats. Methods A total of 60 male SD rats were randomly divided into group A1（ general gavage by tablet,1 mg/kg,1 time/d,n = 10）,group A2（ slow-release gavage by tablets,1 mg/kg,1 time/d,n = 10）,group A3（ slow-release gavage by tablets,0. 5 mg/kg,1 time/d,n = 10）,group B1（ general gavage by oral solution,1 mg/kg,1 time/d,n = 10）,group B2（ slow-release gavage by oral solution,1 mg/kg,1 time/d,n = 10） and B3 group（ slow-release gavage by oral solution,0. 5 mg/kg,1 time/d,n = 10）. The experiment was lasted for 30 d. Survival efficiency and toxic effects including diet condition,body weight,organ lesions,mortality rate and survival time were observed in 6 groups. Results At the 30 thday,the differences in body weight among group A1,A2 and A3 were statistically significant（ P〈0. 01）,and the differences in body weight among group B1,B2 and B3 were also statistically significant（ P〈0. 01）. Mortality rate in group A1 was significantly higher than that in group A2（ P = 0. 025）,and mortality rate in group A2 was significantly higher than that in group A3（ P = 0. 019）. Mortality rate in group B1 was significantly higher than that in group B2（ P = 0. 025）,but there was no significant difference in mortality rate between group B2 and B3（ P = 0. 06）. Low load groups had good survival efficiency and significantly longer survival time,and the differences among groups were statistically significant（ P〈0. 01）. Compared with those in high load groups,numbers of lesions in liver,lung and stomach viscera in low load groups were decreased,and lesion degrees were mild. Conclusion Low dosage slow-release intervention（ 0. 5 mg/kg） of Sirolimus may significantly reduce mortality rate and prolong survival time with less toxic and side-effect and good survival efficiency.
作者
孔祥瑞
李静
周林
肖漓
石炳毅
KONG Xiang-rui;LI Jing;ZHOU Lin;XIAO Li;SHI Bing-yi(Department of Organ Transplant Research,Beijing Key Laboratory of Organ Transplantation and lmmunoloregulation Organ Transplant Institutes of PLA,309 Hospital of PLA,Beijing 100091,China;Department of Health Service,Agency for Offices Administration of General Military Commission,Beijing 100034,China)
出处
《解放军医药杂志》
CAS
2018年第6期1-4,共4页
Medical & Pharmaceutical Journal of Chinese People’s Liberation Army
基金
解放军309医院院内课题(2016MS-003)
