二甘醇腹腔注射与灌胃引起大鼠急性中毒比较

Comparison of acute poisoning induced by intraperitoneal injection or gavage of diethylene glycol in rats

目的比较不同给药途径(腹腔注射和灌胃)引起大鼠二甘醇(DEG)急性中毒的差异。方法30只SD大鼠随机分成两组,分别腹腔注射(IP组)和灌胃(PO组)DEG8ml/kg,于暴露前和暴露后第1,4,7和14天采血测CO2结合率(CO2CP)、肌酐(Scr)、尿素氮(BUN)、丙氨酸氨基转氨酶(ALT)和总胆红素(TBI),收集死亡大鼠及第14天处死大鼠的肾和肝脏组织进行病理检查。结果IP组的死亡率26.7%(4/15),PO组无死亡。在暴露后第1天,IP组的BUN,Scr和ALT水平分别为PO组的2.28,2.91和3.25倍(均P<0.01),其CO2CP下降也显著(13.33±5.97vs22.23±1.37,P<0.01)。第4天,IP组的TBI水平显著高于PO组(89.76±45.48vs44.63±7.59,P<0.05)。第14天,IP组和PO组存活大鼠的各生化指标均恢复到暴露前水平。IP组死亡大鼠的病理改变主要为急性肾小管坏死和肝细胞溶解坏死,而第14天处死的两组大鼠肾和肝脏病理损害均不明显。结论DEG腹腔注射比等剂量灌胃能引起大鼠更严重的中毒反应,提示在进行毒理试验研究和处理临床上的中毒病例时应考虑DEG暴露途径的影响。

Objective To compare the difference in acute poisoning of diethylene glycol （DEG） exposed intraperitoneally and orally in rats. Methods Thirty male SD rats were randomly divided into two equal groups, Groups IP and PO Rats in both groups were given DEG at the dose of 8 ml/kg body weight either intraperitoneally or orally. The level of serum CO2 combining power （ CO2CP） , alanine aminotransferase （ALT） , total bilirubin （TBI） , blood urea nitrogen （BUN） and serum creatinine （Scr） were tested before and 1, 4, 7 and 14 days after exposure. The kidney and liver tissue of all dead or sacrificed rats on 14th day were taken for pathological examinations. Results The mortality of Group IP was 26.7% （4/15） and no death was found in Group PO. On the 1st day after exposure, the levels of BUN, Scr and ALT in Group IP were 2. 28, 2. 91 and 3.25 times higher than that in Group PO, respectively （ P 〈 0. 01 of all items）. Compared to Group PO, the level of CO2CP significantly decreased in Group IP （ 22. 23 ± 1.37 vs 13.33 ± 5.97, P 〈 0. 01 ）. On the 4th day, the level of TBI in Group IP was significantly higher than that in Group PO （ 89. 76 ± 45.48 vs 44. 63 ± 7. 59, P 〈 0. 05 ）. On the 14th day, all biochemical indicators of the survived rats in both Groups returned to the baseline levels. Acute renal tubular and liver cell necrosis were found in dead rats from Group IP. However, no obvious lesions in kidney or liver tissues from the sacrificed rats on the 14th day were found in either groups. Conclusion DEG is more toxic when given intraperitoneally than orally at the same dose in rats, indicating that additional attention should be paid to the route of exposure in toxicological researches and clinical treatment of DEG.