Wu Zhi-Ming, Wen Tao, Tan Yu-Fen, Liu Yan, Ren Feng, Wu Hao
Division of Hepatitis Institute, Beijing You-An Hospital Affiliated with Capital University of Medical Sciences, Beijing, China.
Basic Clin Pharmacol Toxicol. 2007 Feb;100(2):115-20. doi: 10.1111/j.1742-7835.2007.00020.x.
In the present study, we investigated the hepatoprotective effects of salvianolic acid A, a novel antioxidant, against oxidative stress and acute liver injury induced by carbon tetrachloride (CCl(4)) in rats, and the mechanisms underlying its protective effects. Administration of CCl(4) to rats caused severe hepatic damage, as demonstrated by the significant increase in the levels of serum alanine aminotransferase, aspartate aminotransferase and classic histological changes including hepatocyte necrosis or apoptosis, haemorrhage, fatty degeneration, etc. Co-treatment with salvianolic acid A (20 mg/kg, intraperitoneally), a water-soluble extract from a Chinese traditional drug, Radix Salvia miltiorrhiza, significantly decreased CCl(4)-induced hepatotoxicity. Salvianolic acid A not only decreased serum alanine aminotransferase, aspartate aminotransferas levels and ameliorated histopathological manifestations in CCl(4)-treated rats, but also reduced oxidative stress, as evidenced by decreased reactive oxygen species production and malondialdehyde concentrations in the liver tissues, combined with elevated hepatic superoxide dismutase activity and gluthathione content. In addition, salvianolic acid A treatment remarkably reduced intrahepatic tumour necrosis factor-alpha concentrations and caspase-3 activities as compared with the CCl(4)-treated rats. The results suggested that treatment with salvianolic acid A provides a potent protective effect against acute hepatic damage caused by CCl(4) in rats, which may mainly be related to its antioxidative effect.
在本研究中,我们调查了新型抗氧化剂丹酚酸A对大鼠四氯化碳(CCl₄)诱导的氧化应激和急性肝损伤的肝保护作用及其保护作用的潜在机制。给大鼠注射CCl₄会导致严重的肝损伤,血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶水平显著升高以及包括肝细胞坏死或凋亡、出血、脂肪变性等典型组织学变化可证明这一点。与一种来自传统中药丹参的水溶性提取物丹酚酸A(20 mg/kg,腹腔注射)共同处理,可显著降低CCl₄诱导的肝毒性。丹酚酸A不仅降低了CCl₄处理大鼠的血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶水平并改善了组织病理学表现,还减轻了氧化应激,这表现为肝组织中活性氧生成和丙二醛浓度降低,同时肝超氧化物歧化酶活性和谷胱甘肽含量升高。此外,与CCl₄处理的大鼠相比,丹酚酸A处理显著降低了肝内肿瘤坏死因子-α浓度和半胱天冬酶-3活性。结果表明,丹酚酸A处理对大鼠CCl₄诱导的急性肝损伤具有强大的保护作用,这可能主要与其抗氧化作用有关。