亚硫酸氢钠穿心莲内酯对小鼠和家兔的肾毒性作用

目的观察亚硫酸氢钠穿心莲内酯(ASB)的肾毒性作用。方法 30只ICR小鼠随机分为正常对照组、ASB150和1000mg.kg-1组,ASB组小鼠尾静脉iv给予ASB,每天1次,连续7d,正常对照组iv给予等体积生理盐水,检测体重、肾脏系数、血常规、血清尿素氮和肌酐浓度,观察肾脏组织病理变化等指标。18只新西兰家兔,随机分为对照组、ASB125和500mg.kg-1组,麻醉后单次经耳缘静脉iv给予ASB,导尿管法收集尿液并测定尿量及尿常规指标。结果与正常对照组比较,ASB1000mg.kg-1可使小鼠血清肌酐和尿素氮浓度分别从124±19和18±3升高至197±35和(35±10)mmol.L-1(P<0.05),并使外周血白细胞从(10.5±2.0)×109L-1升高至(13.7±3.4)×109L-1,血小板从(666±122)×109L-1降低至(451±207)×109L-1,淋巴细胞比例从(0.83±0.03)降低至(0.68±0.11)(P<0.05),7/10小鼠肾脏出现间质性肾炎,伴轻度纤维化,部分肾小管有蛋白,近曲小管浊肿;与正常对照组比较,ASB150mg.kg-1对小鼠上述指标无明显影响。ASB500mg.kg-1可引起家兔尿蛋白和酮体阳性检出率一过性增加,给药后120min总尿量明显增加(P<0.05);与正常对照组比较,ASB125mg.kg-1对家兔上述指标无明显影响。结论 ASB1000mg.kg-1和500mg.kg-1时分别对小鼠和家兔肾脏具有毒性作用。

Toxic actions of andrographolide sodium bisulfite on kidneys of mice and rabbits

OBJECTIVE To observe the renal toxicity of andrographolide sodium bisulfite (ASB). METHODS Thirty ICR mice were randomly divided into normal control, ASB 150 and 1000 mg·kg^-1 groups, with 10 mice in each group. Mice in ASB groups were iv given ASB 150 and 1000 mg·kg^-1 by tail vein, once daily, for 7 d. The body weight, renal index, blood routine, serum urea nitrogen and creatinine were assessed, and histopathological changes in renal tissues were detected. Eighteen New Zealand rabbits were randomly divided into normal control, ASB 125 and 500 mg·kg^-1 groups, with 6 rabbits in each group. Rabbits in ASB 125 and 500 mg·kg^-1 groups were iv given ASB slowly by ear vein only once after anesthesia. Using catheter method to collect urine, the urine volume and urinalysis were determined. RESULTS Compared with normal control group, serum creatinine and urea nitrogen concentrations in ASB 1000 mg·kg^-1 group increased from 124±19 and 18±3 to 197±35 and (35±10)mmol·L^-1, respectively, and white blood cells elevated from (10.5±2.0)×10⁹ L^-1 to (13.7±3.4)×10⁹ L^-1, platelets reduced from (666±122)×10⁹ L^-1 to (451±207)×10⁹ L^-1, the proportion of lymphocytes reduced from (0.83±0.03) to (0.68±0.11), and 7/10 mice in this group exhibited interstitial nephritis with mild fibrosis, some protein in some tubules, and cloudy swelling of proximal convoluted tubules. While compared with normal control group, ASB 150 mg·kg^-1 had no significant effect on these indicators. ASB 500 mg·kg^-1 also increased significantly the total urine volume of rabbits and the positive rate of protein and ketobody indicators in urine. Compared with normal control group, ASB 125 mg·kg^-1 showed no significant impact on these indicators. CONCLUSIONASB has toxic actions on kidneys of mice and rabbits when ASB is 1000 mg·kg^-1 for mice and 500 mg·kg^-1 for rabbits.