浙江医学2016，Vol.38Issue(15)：1230-1233,1245,5.
对氧磷酶1过表达对敌敌畏急性中毒小鼠肝损伤保护作用的研究
Over-expression of PON1 protects mice from dichlorvos poisoning-induced liver injury
摘要
Abstract
Objective To investigate the effect of over expression of paraoxonase 1 gene(PON1) on inflammation and liver injury induced by dichlorvos (DDVP) poisoning in mice. Methods Ninety six Balb/c mice were randomly divided into 4 groups:normal control group, the dichlorvos poisoning group (9 mg/kg dichlorvos), blank lentivirus group (Lv- GFP + dichlorvos) and PON1 recombinant lentivirus group (Lv- PON1+dichlorvos) with 24 mice in each group. The Lv- GFP, Lv- PON1 were transfected to mice via tail vein in Lv- GFP and Lv- PON1 groups and 9 mg/kg dichlorvos solution were intraperitoneal injected to mice 3 days after transfection, while same amount of saline solution was given to normal control group. At 6 h, 12 h, 24 h, 48 h after dichlorvos injection, 6 mice were sacrificed in batch. Serum acetylcholinesterase (AChE), alanine aminotransferase (ALT) and aspartate transaminase (AST) were measured with chemical colorimetry. The levels of tumor necrosis- α(TNF- α) and interleukin 1β(IL-1β) in liver tissue were determined by enzyme- linked immunosorbent (ELISA). The expression of NF- κBp65 in liver tissue was detected by Western blot. The pathological changes of liver tissue were observed with HE staining. Results Compared with normal control group, the AChE activity decreased and ALT, AST activity increased at 6 h, 12 h, 24 h after dichlorvos injection (P<0.05). Compared to dichlorvos group at corresponding time points, the AChE activity of Lv- PON1+dichlorvos group was significantly increased, and ALT, AST activity significantly decreased(P<0.05). Compared with normal control group, the TNF- α, IL- 1β, and NF- κBp656 levels in dichlorvos group at 6 h, 12 h, 24 h, 48 h were elevated (P<0.05). Compared with dichlorvos group at corresponding time points, the TNF- α, IL- 1βlevels and NF- κBp65 expression in Lv- PON1+dichlorvos group were significantly decreased (P<0.05), expect the IL- 1β expression in 48h. Compared with the Lv- PON1+dichlorvos group, liver injury in dichlorvos group at 12h were significantly severe. Conclusion Over expression of PON1 can reduce inflammation and protect the liver injury induced by acute dichlorvos poisoning in mice, which is associated with down- regulation of NF- κBp65 expression and reduced TNF- α, IL- 1βlevels.关键词
敌敌畏/对氧磷酶1/肝损伤/炎症Key words
Dichlorvos/PON1/Liver injury/Inflammation引用本文复制引用
陈晓宇,郭瑞娟,王菲,吴斌,洪广亮,赵光举,李萌芳,邱俏檬,卢中秋..对氧磷酶1过表达对敌敌畏急性中毒小鼠肝损伤保护作用的研究[J].浙江医学,2016,38(15):1230-1233,1245,5.基金项目
浙江省“十二五”重点学科建设计划资助；浙江省中医药重点学科建设计划（2012- XK- A28）；浙江省医学创新学科建设计划 （）
