丹参酮ⅡA对损伤肝细胞的保护作用及活化肝星状细胞的抑制作用  

Tanshinone ⅡA:protection against damage in cultured hepatocytes and inhibition of activated hepatic stellate cells

作　　者：郭晓红[1] 刘立新[1] 张东梅[1] 张骞骞[1] 

机构地区：[1]山西医科大学第一医院科研实验中心,太原030001

出　　处：《中国药物与临床》2009年第1期13-17,共5页Chinese Remedies & Clinics

基　　金：国家教育部留学归国人员科研启动基金(2005383);山西省高等学校青年学术带头人资助项目(2005017);山西省科技攻关基金项目(051092);太原市科技明星专项基金(070204004)

摘　　要：目的探索丹参酮ⅡA对体外培养肝细胞株HL-7702的安全使用剂量并观察丹参酮ⅡA对肿瘤坏死因子α(TNF-α)和过氧化氢(H2O2)所致体外培养肝细胞损伤的保护作用;同时探讨丹参酮ⅡA对活化肝星状细胞增殖的抑制作用。方法体外培养人肝细胞株HL-7702,加入不同浓度的丹参酮ⅡA,通过MTT比色法检测肝细胞存活率并检测培养上清液中丙氨酸转氨酶(ALT)和乳酸脱氢酶(LDH)含量的变化。建立TNF-α和H2O2所致肝细胞损伤模型,测定培养上清液中的ALT和LDH含量,同时用MTT比色法检测肝细胞存活率。体外培养大鼠肝星状细胞株HSC-T6,加入不同浓度的丹参酮ⅡA,通过MTT比色法检测肝星状细胞存活率。结果①丹参酮ⅡA在一定的剂量范围内对肝细胞无细胞毒性,超过该剂量时,其细胞毒性表现为细胞存活率下降和肝细胞合成分泌的ALT、LDH水平增高。②丹参酮ⅡA可改善TNF-α所致肝细胞存活率下降及ALT、LDH水平的增高。③丹参酮ⅡA可改善H2O2所致肝细胞存活率的下降。④丹参酮ⅡA可抑制活化肝星状细胞的增殖。结论①丹参酮ⅡA对于体外培养肝细胞株(HL-7702)的安全剂量范围为1～2μg/ml。②丹参酮ⅡA在安全剂量范围内能改善TNF-α和H2O2所致体外培养人肝细胞株的损伤。③丹参酮ⅡA在25～100μg/ml的剂量范围内可以有效抑制活化肝星状细胞的增殖。Objective To explore the safe dose range of Tanshinone Ⅱ A in cultured hepatocytes, the protective effect of Tanshinone Ⅱ A in TNF-α and H2O2 damage models, and the inhibitory action of Tanshinone Ⅱ A against activated hepatic stellate cells. Methods Human hepatocyte line HL-7702 was cultured in vitro and treated with different concentrations of Tanshinone Ⅱ A, then the survival of hepatocytes was detected by MTT assay and the changes in supernate level of ALT and LDH were studied. The same measurement was performed in established models of hepatocyte damage induced by tumor necrosis factor α （TNF-α） and H2O2. Rat HSC-T6 was cultured in vitro and treated with different concentrations of Tanshinone Ⅱ A. Cell survival of HSC was detected by MTT assay. Results ①Tanshinone Ⅱ A showed no cytotoxicity for hepatocytes within a certain dose range. Beyond certain dose limits, there was a reduction in cell survival of hepatocyte and increase in supernate levels of ALT and LDH.②Tanshinone Ⅱ A led to improvements in reduced hepatocyte survival and increased supernate levels of ALT and LDH as induced by TNF-α.③ Tanshinone Ⅱ A also led to improvements in reduced hepatocyte survival as induced by H2O2. ④Activated HSC could be inhibited with Tanshinone ⅡA. Conclusion ①The safe dose range of Tanshinone Ⅱ A in cultured hepatocyte （HL- 7702） is 1-2 mg/L. ②The damage induced TNF-α（20μg/L） and H2O2 （7.5-15 mmol/L） could be improved by Tanshinone Ⅱ A within the safe dose range. ③Activated HSC could be inhibited with 25-100 μg/ml Tanshinone Ⅱ A.

关 键 词：肿瘤坏死因子类 过氧化氢 肝细胞 丹参酮 

分 类 号：R285.5[医药卫生—中药学] R286.0[医药卫生—中医学]