【摘要】 目的 研究HIV阻断母婴传播(prevention of mother to child transmission, PMTCT)联合药物方案齐夫多定(zidovudine, AZT)+拉米夫定(lamivudine, 3TC)+克力芝(lopinavir/ritonavir, LPV/r)(简称联合药物)对大鼠的亚急性毒性效应。方法 将72只成年SD大鼠随机分为联合药物高、中、低剂量组和对照组，每组18只大鼠(9♀+9♂),分别给予浓度为2.00、0.65、0.22g/kg(以有效成分计)的药物及纯水，每天给大鼠灌胃受试物1次，连续28 d;观察大鼠的一般情况、行为表现和体重变化，实验结束进行血常规、生化指标和淋巴细胞凋亡率检测，并对主要脏器进行病理组织学检查。结果 给予联合药物后，高、中、低剂量雄鼠及高剂量雌鼠总增重小于对照组(P<0.01)。与对照组比较，三个联合药物组雄雌鼠的肝脏/体重增大(P<0.01或0.05),高剂量组雄雌鼠肾脏、脾脏及脑/体重比值均大于对照组(P<0.01),而高、中剂量雌鼠胸腺/体重比值则减小(P<0.05)。高、中剂量组雄雌鼠的HGB及高、中剂量组雄鼠的RBC均低于对照组(P<0.01或0.05);高、中剂量组雄雌鼠的WBC高于对照组(P<0.01或0.05);3个剂量组雄鼠外周血淋巴细胞凋亡率均高于对照组(P<0.01或0.05)。与对照组比较，3个剂量组雌雄鼠的ALP、高剂量组雌雄鼠的ALT和LDH、高、中剂量组雄鼠的GGTP及高剂量组雄鼠Glu均升高(P<0.01或0.05);3个剂量组大鼠血清TP和Alb均低于对照组(P<0.01)。高剂量组雄雌大鼠BUN及高、低剂量组雄鼠Cr高于对照组(P<0.05)。3个剂量组大鼠血清Ca水平下降(P<0.01或0.05)。病理学检查发现，联合药物组部分大鼠的甲状腺滤泡增生，胶质减少，脾脏脾窦内RBC增多而淋巴细胞减少。结论 在本实验条件下，AZT+3TC+LPV/r联合药物对于大鼠具有潜在的亚急性毒性。更多还原

【Abstract】 Objective To study the subacute toxic effects of prevention of mother to child transmission(PMTCT) of human immunodeficiency virus(HIV) combined drugs of zidovudine(AZT) + lamivudine(3TC) + lopinavir/ritonavir(LPV/r) on rats. Methods Seventy two adult SD rats were randomly divided into the high, medium and low dose groups and the control group, with 18 rats in each group(9 males and 9 females). The rats were given drugs by gavage with the concentrations of 2.00, 0.65 and 0.22 g/kg(based on active ingredients) and pure water, once a day for 28 days, respectively. The rats’ general condition, behavior and weight changes were observed. At the end of the experiment, blood routine, biochemical indexes and lymphocyte apoptosis rate were detected, and the main organs were examined by histopathology. Results After administration of the combined drugs, the total weight gain of male rats in the high, medium and low dose groups and female rats in the high dose group was less than that of the control group(P<0.01). Compared with the control group, the liver/body weight of male and female rats in the three combined drug groups increased(P<0.01 or 0.05). The ratios of kidney/body weight, spleen/body weight and brain/body weight of male and female rats in the high dose group were all higher than those in the control group(P<0.01), while the ratio of thymus/body weight of female rats in the high and medium dose groups decreased( P<0.05). HGB of male and female rats in the high and medium dose groups and RBC of male rats in the high and medium dose groups were all lower than those in the control group( P<0.01 or 0.05). WBC of male and female rats in the high and medium dose groups was higher than that in the control group( P< 0. 01 or 0. 05). The apoptosis rate of peripheral blood lymphocytes in male rats of the three dose groups was higher than that in the control group( P< 0. 01 or 0. 05). Compared with the control group,these indicators increased,including ALP of male and female rats in the three dose groups,ALT and LDH of male and female rats in the high dose group,GGTP of male rats in the high and medium dose groups and Glu of male rats in the high dose group( P<0.01 or 0.05). Serum TP and Alb in the three dose groups were lower than those in the control group( P<0.01). BUN of male and female rats in the high dose group and Cr of male rats in the high and low dose groups were higher than those in the control group( P < 0. 05). Serum Ca of rats in three dose groups decreased( P<0.01 or 0.05). Pathological examination showed that some rats in the combined drug group had follicular hyperplasia and decreased glia in the thyroid gland as well as increased red blood cells and decreased lymphocytes in the splenic sinuses of spleen. Conclusion Under the experimental conditions,AZT + 3TC +LPV/r combination drug has potential subacute toxicity to rats.更多还原