亚致死剂量马拉硫磷导致小鼠肾损伤及内质网应激分析

The Kidney Injury and Endoplasmic Reticulum Stress Induced by Long-term Sublethal Dose of Malathion in Mice

[目的]探讨有机磷化合物对哺乳动物肾组织的毒效作用,为有机磷的非胆碱能毒理机制研究提供参考。[方法]选取马拉硫磷为有机磷代表,分别以1/3 LD50、1/10 LD50、1/25 LD50亚致死剂量马拉硫磷经口灌胃小鼠18 d,苏木精-伊红(HE)染色观察各组肾组织病理变化情况,荧光定量PCR和免疫组织化学染色法测定药物处理前后肾组织DDIT3基因的m RNA和蛋白表达情况。[结果]亚致死剂量马拉硫磷可以升高小鼠血液中的血尿素氮、肌酐、尿酸含量。HE染色显示,与对照组比较,1/3 LD50和1/10 LD50剂量组对小鼠肾小球、肾小囊腔内、肾静脉血管损伤显著。荧光定量PCR和IHC结果显示,马拉硫磷可显著升高小鼠肾组织中内质网应激的标志基因DDIT3的m RNA水平和蛋白表达。[结论]以上结果提示,亚致死剂量马拉硫磷可致肾组织损伤,增加肾细胞的内质网应激,诱导肾细胞凋亡可能是其产生损伤的原因之一。

[Aims]This study aims to explore the toxic effect of organophosphorus compounds on mammalian kidney tissue,and provide reference for the study of non-cholinergic toxic mechanism of organophosphorus compounds.[Methods]Malathion was selected as the representative of organophosphorus compounds,and 1/3 LD50,1/10 LD50and1/25 LD50sublethal doses of malathion were orally administered to mice for 18 days.HE staining was used to observe the pathological changes of renal tissue in each group.The m RNA and protein expression of DDIT3 gene in renal tissue before and after drug treatment were determined by fluorescence quantitative PCR and immunohistochemistry (IHC).[Results]Long-term sublethal dose of malathion could increase the urea nitrogen,creatinine and uric acid levels of blood in mice.HE staining showed that 1/3 LD50and 1/10 LD50dose of malathion had significant damage to the glomeruli,renal capsule cavity and renal vein blood vessels of mice.The results of fluorescence quantitative PCR and IHC showed that malathion could significantly increase the gene DDIT3 mRNA level and protein expression,which as one of the main gene of endoplasmic reticulum stress.[Conclusions]The above results suggested that malathion can cause renal tissue damage after long-term sublethal dose in mice,and increasing cellular endoplasmic reticulum stress and then inducing the renal cells apoptosis may be one of the reasons for its damage.