新型重组人肿瘤坏死因子对大鼠肝细胞及小鼠肝组织中钙稳度的影响  

Effect of rhTNF-NC on calcium homeostasis in cultured rat hepatocytes and mouse livers

作　　者：颜天华[1] 袁伯俊[2] 刘俊平[2] 张淑英[2] 吴浩[2] 

机构地区：[1]南京军医学院药理学教研室,南京210049 [2]第二军医大学基础医学部卫生毒理学教研室,上海200433

出　　处：《第二军医大学学报》2000年第1期20-23,共4页Academic Journal of Second Military Medical University

基　　金：国家新药研究基金!资助项目(96-90154

摘　　要：目的：研究新型重组人肿瘤坏死因子（ｒｈＴＮＦ－ＮＣ）对培养大鼠肝细胞内游离Ｃａ２＋ 浓度（［Ｃａ２＋ ］ｉ）及小鼠肝组织中Ｃａ２＋ 含量的影响。方法：以Ｆｕｒａ－２／ＡＭ 为Ｃａ２＋ 荧光检测，荧光分光光度法测定培养大鼠肝细胞内［Ｃａ２＋ ］ｉ；原子吸收分光光度法测定小鼠肝组织中Ｃａ２＋ 含量。结果：在加入ｒｈＴＮＦ－ＮＣ３ ｈ 后，可剂量依赖性地引起培养大鼠肝细胞内［Ｃａ２＋ ］ｉ 显著升高；ｒｈＴＮＦ－ＮＣ可使Ｄ－ＧａｌＮ 致敏小鼠出现严重肝损伤，肝组织中Ｃａ２＋ 含量明显增加，钙通道阻滞剂维拉帕米、硝苯地平能显著降低肝组织中Ｃａ２＋ 含量，同时减轻肝损伤程度。结论：ｒｈＴＮＦ－ＮＣ可引起培养大鼠肝细胞及小鼠肝组织中钙稳度失调，钙通道阻滞剂通过减少Ｃａ２＋Objective: To investigate the effect of rhTNF NC on free cytosolic Ca 2+ concentration ([Ca 2+ ] i) in cultured rat hepatocytes and Ca 2+ contents in mouse livers. Methods: [Ca 2+ ] i was measured by fluorescence spectrophotometer with Ca 2+ detector Fura 2/AM and Ca 2+ contents in mouse livers were examined by atomic absorption spectrophotometer. Results: rhTNF NC dose dependently and significantly increased [Ca 2+ ] i 3 h after it was added into culture medium. rhTNF NC also dramatically increased Ca 2+ contents in mouse livers and induced serious liver injury in mice previously sensitized with D GalN. Calcium antagonists verapamil and nifedipine obviously decreased Ca 2+ contents and attenuated liver injury. Conclusion: Ca 2+ homeostasis in cultured rat hepatocytes and mouse livers is disordered by rhTNF NC. Verapamil and nifedipine can attenuate liver injury induced by rhTNF NC by decreasing Ca 2+ accumulation.

关 键 词：肿瘤坏死因子 肝损伤 钙稳度 rhTNF-NC 

分 类 号：R575.02[医药卫生—消化系统]