湿热环境暴露对氰化钠毒性和组织氧化应激反应的影响

摘要

目的 探讨湿热环境下氰化物毒性作用变化规律及其对组织氧化应激反应的影响.方法 以小动物湿热环境试验箱模拟高温高湿环境,测定不同温、湿度[温度(Ta)(20±0.5)℃、相对湿度(50±5)%,温度36℃及38℃、相对湿度(RH)(60±3)%]条件下氰化钠经腹腔注射KM小鼠的LD50.另将30只SD大鼠随机分为常温对照、常温中毒、湿热对照、湿热中毒及药物预防组,各组受试动物分别按以下因素单一或联合处理:(1)湿热应激:模拟箱内[温度(38±0.5)℃,相对湿度(60±3)%]60 min;(2)氰中毒:动物腹腔注射氰化钠3.6 mg/kg;(3)药物预防:给予谷胱甘肽、维生素C灌胃5 d.各组受试动物于热应激后60 min和(或)中毒30 min后测定脑、肝组织匀浆超氧化物歧化酶(superoxide dismutase,SOD)活性和丙二醛(malondialdehyde,MDA)含量.结果 与20℃,RH 50%时KM小鼠氰化钠中毒LD50(4.77 mg/kg)相比,(36±0.5)℃或(38±0.5)℃,RH 60%湿热环境中毒动物的LD50分别下降至4.66 mg/kg(P>0.05)及4.17 mg/kg(P<0.05).20℃ RH 50%条件下NaCN中毒后肝、脑组织SOD活力下降(P<0.01),MDA含量增加(P<0.01),而38℃RH 60%环境下NaCN中毒所致氧化应激改变更明显(P<0.01).药物预防可缓解相同条件下上述指标的改变(P<0.01).结论 暴露于湿热环境下,小鼠氰化纳中毒的LD50可随环境温度的升高而降低.湿热环境和(或)氰化钠中毒两因素均可导致氧化应激指标的明显改变,二者同时作用可能具有联合效应.服用抗氧化药物可提高组织抗氧化应激能力.%Objective To investigate the impact of heat-humid environment (HHE) on sodium cyanide ( NaCN ) toxicity and tissue responses to oxidative stress. Methods An animal experimental chamber with adjustable internal temperature and relative humidity(RH) was used to simulate HHE. The LD50 value of mice exposed to 20℃ air temperature (Ta) with 50% RH, or Ta 36℃; and 38℃; with RH 60% was determined by injecting NaCN intraperitoneally after pre -exposure for 1 hour. Another 30 rats were randomly divided into 5 groups, i. e. , control group, intoxication group, HHE stress group, HHE combined intoxication group and preventive drug group . Each group of test animals was treated with the following sin -gle or combined treatment. (1 ) HHE conditions in the chamber were (38 ±0. 5)℃ with RH 60% . (2) NaCN intoxication was created by intraperitoneally injecting NaCN (3.6 mg/kg, i. p. ). (3) Drug preventive treatment was intragastric administration of reduced glutathione (GSH) and vitamin C (VitC) for 5 d. The activities of superoxide dismutase (SOD) and the content of malondialdehyde ( MDA) in the liver and brain were determined biochemically 60 min after HHE and/ or 30 min after intoxication stress respectively. Results Compared with the LD50 (4.77 mg/kg) of mice exposed to the normal ambient condition[ (20 ±1)℃ with RH (50 ±10)%], the LD50 of mice exposed to Ta (36 ±0.5)℃ or (38 ±0.5)℃ with RH60% was decreased to 4.66 mg/kg (P>0.05) and 4.17 mg/kg (P<0.05). The MDA content was significantly increased (P <0.01 ) and the SOD activities were obviously decreased (P <0.01) in the liver and brain after NaCN injec-tion rnin the intoxication group (P <0. 01 ) ,especially in the HHE with intoxication group (P <0.01 ). Preventive drug administration could significantly reverse the changes in oxidative stress parameters ( P < 0. 01 ). Conclusion The LD50 of NaCN intoxication in mice is reduced with the increase in the ambient temperature when exposed to a heat -humid environment. HHE and/or NaCN administration can significantly weaken the tissue response to oxidative stress . Pretreatment with Vit C and GSH may restore tissue anti -oxidative ability under the same condition.