目的 探讨对氧磷酶3（PON3）对急性中毒肝损伤的保护作用及作用机制。 方法 将40只Balb/c小鼠随机分为4组，正常对照（NC）组、敌敌畏（DDVT）对照组、绿色荧光蛋白慢病毒（Lv-GFP）组和重组PON3慢病毒（Lv-PON3）组，每组10只。LV-GFP组和Lv-PON3组小鼠经尾静脉分别注射2×10⁷ TU的Lv-GFP、Lv-PON3慢病毒，3 d后腹腔注射敌敌畏（DDVT）溶液9 mg/kg，DDVT组只需腹腔注射同等剂量DDVT，NC组注射同等剂量生理盐水。各组于DDVT染毒后12 h麻醉处死10只小鼠取肝组织，ELISA法检测各组血清乙酰胆碱酯酶（AChE）、肝功能指标谷丙转氨酶（ALT）和谷草转氨酶（AST）和肝组织氧化应激指标丙二醛（MDA）、过氧化氢酶（CAT）、超氧化物歧化酶（SOD）和谷胱甘肽（GSH），HE染色法观察肝组织形态学改变，Real-time PCR检测肝组织Kelch样环氧氯丙烷相关蛋白-1（Keap1）、血红蛋白加氧酶（HO-1）和转录因子NF-E2相关因子2（Nrf2） mRNA的表达。 结果 与NC组比较，DDVT组和Lv-GFP组肝组织MDA、ALT、AST水平，HO-1和Nrf2 mRNA表达量明显升高，AChE、CAT、SOD、GSH水平和Keap1 mRNA表达量均明显降低（P<0.05）。与DDVT组比较，Lv-PON3组肝组织MDA、ALT、AST水平，Keap1 mRNA表达量降低，AChE、CAT、SOD和GSH水平均明显著升高，HO-1和Nrf2 mRNA表达量显著上升（P<0.05）。正常对照组肝细胞结构清晰，未出现肝细胞坏死和脂肪病变的情况，DDVT组和Lv-GFP组出现肝细胞坏死和脂肪变性等病理改变，Lv-PON3组肝脏病变组织肝细胞坏死和脂肪变性细胞数有一定的减少。 结论 PON3可通过Keap1-Nrf2/HO-1途径缓解氧化应激反应，改善肝功能，对敌敌畏急性中毒小鼠肝损伤有一定的保护作用。

Objective To investigate the protective effect and mechanism of oxidative sulfasalase 3 on acute poisoned liver injury. Methods Forty Balb/c mice were randomly divided into 4 groups: normal control (NC) group, dichlorvos (DDVT) control group, green fluorescent protein lentivirus (Lv-GFP) group, and recombinant paraoxonase 3(PON3) lentivirus (Lv-PON3) group, 10 in each group.Mice in Lv-GFP and Lv-PON3 group were injected with 2×10⁷ TU of Lv-GFP and Lv-PON3 lentiviruses via the tail vein respectively. After 3 days, they were intraperitoneally injected with a solution of dichlorvos (DDVT) 9 mg/kg.The same dose of DDVT was injected intraperitoneally into the DDVT group, and the same dose of saline was injected into the NC group.In each group, 10 mice were killed by anesthesia 12 hours after DDVT exposure to take liver tissue. ELISA was used to detect serum acetylcholinesterase(AChE), liver function indexes alamine aminotransferase(ALT) and aspartate aminotransferase(AST) and oxidative stress indexes malondialdehyde(MDA), catalase(CAT), superoxide dismutase(SOD) and glutathione(GSH) in liver tissues of each group. HE staining was used to observe the morphological changes of liver tissues. Results Compared with the NC group, the levels of MDA, ALT, AST, hemoglobin oxygenase 1(HO-1) and Nrf2 mRNA expression were significantly increased in DDVT group and Lv-GFP group, and AChE, CAT, SOD, GSH levels and Kelch-like epichlorohydrin-associated protein 1(Keap1)mRNA were significantly decreased (P<0.05). Compared with the DDVT group, the levels of MDA, ALT, AST and Keap1mRNA expression in liver tissue were significantly decreased in Lv-PON3 group, and AChE, CAT, SOD, GSH levels and HO-1 and Nrf2 mRNA expression were significantly increased (P<0.05). The structure of hepatocytes in the normal control group was clear, no hepatocyte necrosis and fat lesions were seen. Pathological changes such as hepatocyte necrosis and fatty degeneration under light microscope in DDVT and Lv-GFP groups, the number of hepatocyte necrosis and steatosis cells in the liver lesions of the Lv-PON3 group were reduced. Conclusion PON3 can alleviate oxidative stress and improve liver function through Keap1-Nrf2/HO-1 pathway, which has a certain protective effect on liver damage induced by acute poisoning of dichlorvos in mice.