口服埃洛石纳米管对小鼠大肠的亚急性毒性及其恢复情况

Oral halloysite nanotubes-induced subacute toxicity in the large intestine of mice and recovery

天然埃洛石纳米管(HNTs)具有空心腔结构,它作为传统中药、药物载体、化妆品、饲料添加剂、抗菌材料、污水处理剂等广泛地应用于许多领域.然而目前人们对埃洛石纳米管诱导的肠道毒性仍不清楚.本文研究口服HNTs对小鼠大肠亚急性毒性及其恢复情况.结果表明,小鼠连续30天口服低剂量(5 mg/kg)HNTs,未对其大肠造成明显的Al和Si聚集和损伤.小鼠连续30天口服高剂量(50 mg/kg)HNTs,导致其大肠中Al和Si聚集和氧化应激反应,表现为大肠中谷胱甘肽过氧化物酶活性和超氧化物歧化酶活性显著降低,以及脂质氧化产物丙二醛含量显著升高.该氧化应激导致大肠细胞炎症反应,表现为大肠组织中一氧化氮合酶和环氧化酶-2的表达水平升高以及炎细胞浸润病变.这说明口服高剂量HNTs能引起由一氧化氮合酶参与的大肠损伤.高剂量组小鼠口服给药30天后再经过30天恢复期,未发现其大肠组织有明显损伤,说明口服高剂量HNTs引起的小鼠大肠的急性毒性是可逆的和可以恢复的.

Natural halloysite nanotubes(HNTs)with a hollow lumen have been widely applied in many fields,such as traditional Chinese medicines,drug carriers,cosmetics,feed additives,antibacterials and water purification.However their toxicity in the gastrointestinal tract is still unclear.The aim of this study is to evaluate subacute oral toxicity of HNTs in the large intestines of mice and their recovery from it.Oral HNTs at low dose(5 mg/kg)for 30 days had no obvious adverse effect on the large intestine.Oral HNTs at high dose(50 mg/kg)for 30 days induced Al and Si accumulation and oxidative stress in the large intestine as indicated by the significant decreases in GSH-Px and SOD activities and the significant increase in MDA level in the large intestine,which caused significant increases in COX-2 and iNOS levels and inflammatory response and iNOS-mediated damages in the large intestine.Oral HNTs-induced changes at high dose described above were not observed after a 30 days recovery period,suggesting that oral HNTs-induced subacute toxicity in the large intestine was reversible.