α-萘异硫氰酸酯致小鼠胆汁淤积肝损伤作用的研究  

Effects and mechanisms of α-naphthalene isothiocyanate on liver in mice

作　　者：罗琳[1] 梁烨莹[1] 王蓬波[2] 窦志华[3] 张琳[3] 王凯[1] 张伟[1] 

机构地区：[1]南通大学医学院药理系,江苏南通226001 [2]南通瑞慈医院 [3]南通大学附属南通市第三人民医院

出　　处：《毒理学杂志》2012年第5期340-343,共4页Journal of Toxicology

基　　金：江苏省高校自然科学基础研究基金资助项目(08KJB360009);南通市应用研究计划基金资助项目(K2009029);江苏高校优势学科建设工程资助项目;南通大学大学生实践创新训练计划项目

摘　　要：目的研究α-萘异硫氰酸酯(ANIT)对小鼠肝脏的作用,并探讨其可能的作用机制。方法将ICR小鼠随机分成正常对照组和ANIT组(以112 mg/kg剂量的ANIT灌胃给予小鼠),比较两组小鼠的胆汁分泌量,血清TBIL、DBIL、TBA、ALT、AST和ALP值,并观察小鼠肝组织的病理切片和UDPG-T的活性,同时Western blot检测肝组织中NOX4和NTCP的蛋白表达。结果与正常对照组比较,ANIT组血清学指标均明显升高(P<0.01或P<0.05);胆汁分泌量虽较正常对照组略有升高,但差异无统计学意义(P>0.05);肝组织病理切片显示有肝细胞变性坏死、淤胆、炎症细胞与汇管区胆管增生均十分明显;肝组织UDPG-T活性也明显低于正常对照组(P<0.01),而NOX4蛋白表达明显增加,NTCP则表达降低。结论 ANIT能导致小鼠肝脏胆汁淤积和肝功能损伤,该作用可能与肝细胞变性坏死,组织氧化损伤,胆盐代谢和转运能力降低有关。Objective To study the effects and mechanisms of α-naphthalene isothiocyanate on liver in mice. Methods The ICR mice were randomly divided into normal control group and ANIT group, a-naphthalene isothiocyanate （ANIT）in dose of 112 mg·kg-1 was given to mice of ANIT group. Capacity of bile secretion, serum indices such as TBIL, DBIL, TBA, ALT, AST, and ALP, uridine diphosphoglucuronyl transferase （UDPG-T） activity of liver tissue, the pathological changes of liver tissues and the expression of NOX4, NTCP were observed on the 12th day of gestation. Results Compared with normal control group, all serum indices of the ANIT group were significantly increased（ P 〈 0.01 or P 〈 0.05 ）. Capacity of bile secretion of ANIT group was also increased but without statistical significance （ P 〉 0. 05）. UDPG-T activity of liver tissue of ANIT group decreased significantly （ P 〈 0.01 ） , the expression of protein NOX4 increased and NTCP decreased. Pathological examination showed hepatocytes necrosis, cholestasis, inflammatory cell infiltration and bile duct hyperplasia after ANIT administration. Conclusion ANIT can induce cholestasis and liver injury on mice and its mechanism might be related with its effect of impairing hepatocytes, oxidative damage,and decreasing activiy of the bile metabolism and transport.

关 键 词：Α-萘异硫氰酸酯 胆汁淤积 小鼠 

分 类 号：R965[医药卫生—药理学]