Lee Tzung-Yan, Mai Lee-Ming, Wang Guei-Jane, Chiu Jen-Hwey, Lin Yun-Lian, Lin Han-Chieh
Institute of Traditional Medicine, National Yang-Ming University School of Medicine, Taiwan.
J Pharmacol Sci. 2003 Mar;91(3):202-10. doi: 10.1254/jphs.91.202.
The purpose of this study was to investigate the possible mechanisms of Salvia miltiorrhiza (Sm) in carbon tetrachloride (CCl(4))-induced acute hepatotoxicity in rats. Male Wistar rats received a single dose of CCl(4) (2 ml/kg in corn oil, intraperitoneally). Three hours after CCl(4) intoxication, rats received either Sm (100 mg/kg) or silymarin (100 mg/kg) by gastrogavage twice a day for 2 consecutive days. CCl(4)-induced liver damage was shown by significant elevation of serum aminotransferase levels. Additionally, a significant decrease was observed in hepatic microsomal P450 2E1 protein content and hepatic concentrations of antioxidant enzymes. In contrast, rats given both Sm and silymarin supplement had less elevation of serum aminotransferase concentrations associated with less severe lobular damage of hepatocytes than rats receiving CCl(4) alone. Sm administration restored the reduction of hepatic microsomal P450 2E1 protein content as well as inducing an increase in hepatic glutathione concentration. On the other hand, administration of silymarin resulted in an elevation of hepatic superoxide dismutase levels. Moreover, both Sm and silymarin treatment inhibited the elevation of hepatic inducible nitric oxide (iNOS) protein content and nitrite concentration in liver homogenate 24 h after CCl(4) intoxication. We concluded that administration of Sm is effective in amelioration of CCl(4)-induced hepatotoxicity. This effect may be due to its ability to decrease the metabolic activation of CCl(4) by an increase in P450 2E1 protein content and its antioxidant activity associated with less increase in hepatic iNOS protein content.
本研究旨在探讨丹参（Sm）对四氯化碳（CCl₄）诱导的大鼠急性肝毒性的可能作用机制。雄性Wistar大鼠腹腔注射单次剂量的CCl₄（2 ml/kg玉米油）。CCl₄中毒3小时后，大鼠每天经口灌胃给予Sm（100 mg/kg）或水飞蓟宾（100 mg/kg），连续2天。血清转氨酶水平显著升高表明CCl₄诱导了肝损伤。此外，肝微粒体P450 2E1蛋白含量和抗氧化酶的肝脏浓度显著降低。相比之下，给予Sm和水飞蓟宾补充剂的大鼠血清转氨酶浓度升高幅度较小，肝细胞小叶损伤程度也比仅接受CCl₄的大鼠轻。给予Sm可恢复肝微粒体P450 2E1蛋白含量的降低，并诱导肝脏谷胱甘肽浓度增加。另一方面，给予水飞蓟宾可导致肝脏超氧化物歧化酶水平升高。此外，Sm和水飞蓟宾治疗均抑制了CCl₄中毒24小时后肝脏匀浆中肝诱导型一氧化氮（iNOS）蛋白含量和亚硝酸盐浓度的升高。我们得出结论，给予Sm可有效改善CCl₄诱导的肝毒性。这种作用可能是由于其通过增加P450 2E1蛋白含量降低CCl₄代谢活化的能力及其与肝脏iNOS蛋白含量增加较少相关的抗氧化活性。
