石房蛤毒素暴露对F1代小鼠肝损伤及脂质代谢的影响  

Effects of Saxitoxin Exposure on Liver Injury and Lipid Metabolism in the F1 Generation of Mice

作　　者：陈妹 黄海燕[2] 任晓虎[2] 陈效 刘云岗[1] 刘建军[2] CHEN Mei;HUANG Hai-yan;REN Xiao-hu;CHEN Xiao;LIU Yun-gang;LIU Jian-jun(School of Public Health,Southern Medical University,Guangzhou 510515,China;Shenzhen Center for Disease Control and Prevention,Shenzhen Key Laboratory of Modern Toxicology,Shenzhen Medical Key Discipline of Health Toxicology,Shenzhen 518055,China)

机构地区：[1]南方医科大学公共卫生学院,广州510515 [2]深圳市疾病预防控制中心深圳市现代毒理学重点实验室深圳市卫生毒理学医学重点学科,深圳518055

出　　处：《伤害医学(电子版)》2024年第4期31-38,共8页Injury Medicine(Electronic Edition)

基　　金：深圳市基础研究学科布局项目(JCYJ20180508152311822);深圳市医学重点学科建设经费资助项目(SZXK069);深圳市医疗卫生三名工程项目(SZSM202211010)。

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。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,0.20μg/kg,and 2.00μg/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 2.00μg/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 0.02μg/kg,0.20μg/kg,and 2.00μg/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.

关 键 词：石房蛤毒素 脂质组学 肝损伤 

分 类 号：R28[医药卫生—中药学]