Objective To study the effect of amifostine on lung uptake of PQ, and its preventive effect against lung injury. Methods 75 rats were randomly divided into the normal control group (n=S), the model group (n=10, further divided into 8h-model group and 24h- model group according to the samplingtime of 8h and 24h after poisioning, with 5 in each group), and the drug intervention group (n=60). Based on the dosage of amifostine [30mg/kg, 60mg/kg and lOOmg/kg (labelled as L, M and H)], interval time [0.7Sh and l.Sh (labelled with 1 and 2)] and sampling time (8h and 24h). The intervention group was divided into 12 groups: 8h-Ll, 8h-Ml, 8h-Hl, 8h-L2, 8h-M2, 8h-H2, 24h-Ll, 24h-Ml, 24h-Hl, 24h-L2, 24h-M2 and 24h-H2, with 5 rats in each group. Except the normal control group, these rats were poisoned by injecting 3Smg/kg of PQ; After lh, amifostine was injected three times into the rats of the drug intervention groups at different doses and interval time. All the 75 rats were sacrificed at 8h or 24h after poisioning, and lung tissue was harvested, and PQconcentration in the plasma and the lung tissue was determined. The contents of SOD and MDA were assayed. Results The PQ concentration of L drug intervention groups in the lung tissue was significantly lower than that of M and H drug intervention groups and model groups. The PQ_ concentration in the plasma in the drug intervention groups was not different from that in the model groups. Except for the H drug intervention groups, there was no significant change in SOD. Both SOD and MDA contents in the lung tissue were significantly different in the other drug intervention groups (SOD increased obviously while MDA was reduced obviously). SOD in the groups of 0.75h interval time was higher than that in the l.Sh interval time groups. Conclusion Repeated administration of low-dose of amifostine after poisioning can inhibit lung uptake of PQ in rats, and significantly reduce the oxidative damage induced by the PQ_poisoning.%目的 探讨氨磷汀对百草枯(PQ)染毒大鼠肺组织摄取的影响及其对肺损伤的保护作用.方法 雄性Wistar大鼠75只,随机分为正常对照组(n=5)、模型组(n=10)和药物干预组(n=60).模型组按染毒后8h、24h采样再分为8h-模型组和24h -模型组,每组5只；药物干预组根据氨磷汀的使用剂量[30、60、100mg/kg(分别以L、M和H表示)]和用药间隔时间[0.75h和1.5h(分别以1和2表示)]及采样时间(染毒后8h和24h)分为8h-L1、8h-M1、8h-H1、8h-L2、8h-M2、8h-H2、24h-LI、24h-M1、24h-H1、24h-L2、24h-M2和24h-H2组,共12个亚组,每组5只.除正常对照组外,其余各组大鼠均经腹腔注射PQ35mg/kg.染毒后1h,各药物干预组按上述给药剂量及间隔时间腹腔注射氨磷汀各3次,在不同时间(染毒后8h和24h)处死所有动物采样,测定血浆和肺组织中PQ浓度并检测肺组织匀浆超氧化物歧化酶(SOD)和丙二醛(MDA)含量.结果 低剂量药物干预组肺组织PQ含量明显低于模型组及中、高剂量药物干预组(P＜0.05),但不同时间间隔组之间无统计学差异(P＞0.05).各药物干预组血浆PQ农度与模型组比较无统计学差异,各剂量组和各时间间隔组之间比较亦无统计学差异(P＞0.05).与正常对照组比较,模型组肺组织SOD含量显著降低,MDA含量显著升高(P＜0.01).与模型组比较,除高剂量组SOD变化不明显外,其余各剂量药物干预组肺组织SOD和MDA含量均存在统计学差异,即SOD显著升高,MDA显著降低(P＜0.01).各药物干预组之间比较,0.75h间隔组SOD含量明显高于1.5h间隔组(P＜0.01).结论 短期内多次重复给予一定剂量氨磷汀可显著减少PQ肺组织摄取,减轻PQ毒大鼠肺组织的氧化损伤.
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