【摘要】 目的 探讨石房蛤毒素(saxitoxin,STX)暴露对F1代小鼠肝损伤及脂质代谢的影响,为长期STX暴露引起肝毒性机制研究提供依据。方法 60只雌性和30只雄性SPF级C57BL/6J小鼠,雌鼠和雄鼠按照2:1的比例进行合笼,将孕鼠随机分配至对照组以及0.02μg/kg、0.20μg/kg、2.00μg/kg组,经自由饮水方式暴露,每4天更换一次染毒液。待F1代小鼠离乳后将其数量调整为每组8只(雌雄各半),继续经自由饮水染毒。F1代小鼠从孕哺期及发育期持续STX暴露180天后处死,取肝组织进行HE染色及脂质组学分析。结果 长期STX暴露F1代小鼠肝组织HE染色结果 显示,3个剂量染毒组皆出现肝细胞空泡变性,实质内淋巴细胞浸润和出血等组织病理学异常,与对照组相比,2.00μg/kg组肝炎性细胞浸润增多(P=0.009)。脂质组学结果 显示,与对照组相比,0.02μg/kg、0.20μg/kg、2.00μg/kg组甘油二酯(diglyceride,DG)、磷脂酰胆碱(phosphatidylcholine,PC)类脂质水平均呈下调趋势,差异具有统计学意义(P=0.012,P=0.046,P=0.015)。结论 长期STX暴露可引起F1代小鼠肝组织DG、PC类脂质水平的下调,从而诱导肝损伤,其作用机制可能与增加氧化应激反应或炎性细胞浸润增加有关。更多还原

【Abstract】 Objective To investigate effects of saxitoxin(STX) exposure on hepatic injury and on lipid metabolism in the F1generation of mice and to provide information for studying mechanisms of hepatotoxicity.Methods Sixty female and thirty male SPF-grade C57BL/6J mice were mated in a 2:1 ratio.Pregnant mice were randomly divided into 4 groups:the 0.02μg/kg,0.20 μg/kg,and 2.00 μg/kg treatment groups and the control group which was treated with water freely.The treatment solutions were changed every 4 d.After the F1 generation mice were weaned,the number of mice was 8(half male and half female) in each group,and the exposure was continued by free drinking.The F1 mice were exposed to STX for 180 d from gestation and then sacrificed.Liver tissues were extracted and analyzed using HE staining and lipidomics.Results HE staining of liver tissues from the treated F1 mice showed histopathological abnormalities:vacuolar degeneration of hepatocytes,lymphocytic infiltration within the parenchyma,and hemorrhage in all dose groups.The 2.00 μg/kg group showed a significant increase in hepatitis cell infiltration compared to the control group(P=0.009).Lipidomics results showed that,compared with the control group,the levels of diglyceride(DG) and phosphatidylcholine(PC) lipids were significantly down-regulated in the 0.02 μg/kg,0.20 μg/kg,and 2.00 μg/kg groups(P=0.012,P=0.046,P=0.015).Conclusion Chronic exposure to STX in the F1 generation mice led to a downregulation of DG and PC lipid levels in hepatic tissues,which is indicative of hepatic injury.The underlying mechanism of this injury may involve increased oxidative stress or enhanced inflammatory cell infiltration.更多还原