Zhao Jinyan, Hu Haixia, Wan Yun, Zhang Yuchen, Zheng Liangpu, Hong Zhenfeng
Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
Fujian Key Laboratory of Integrative Medicine in Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
Exp Ther Med. 2017 May;13(5):1820-1826. doi: 10.3892/etm.2017.4174. Epub 2017 Mar 2.
Liver damage results from a variety of insults, including hepatitis and chemical toxicity from alcohol, drugs and other toxins. The present study evaluated the hepatoprotective effects and potential mechanisms of action of the Traditional Chinese Medicine Pien Tze Huang Gan Bao (GB) in a rat model of carbon tetrachloride (CCl)-induced liver injury. Sixty male Sprague-Dawley rats were randomly divided into six different groups: i) Control, ii) CCl injury model and groups treated with iii) silymarin as a positive drug control, iv) 150 mg/kg GB, v) 300 mg/kg GB and vi) 600 mg/kg GB. Control rats received no treatment, while the remaining ones were intraperitoneally injected with CCl (2 ml/kg) to induce acute liver disease. Silymarin or GB was orally administered prior to CCl treatment in various treatment groups for 7 days. Animals were sacrificed 24 h post-CCl injection. It was revealed that GB significantly reduced serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma glutamyl transpeptidase and total bilirubin levels in the serum induced by CCl. BG also prevented CCl-induced changes in liver tissues, as revealed by histopathological analysis. CCl-induced reductions in endogenous liver antioxidant enzyme activities of superoxide dismutase, glutathione and glutathione peroxidase as well as increases in malondialdehyde and thiobarbituric acid reactive substances were inhibited by GB treatment. Activated NF-κB in liver tissues was also significantly increased by CCl, which was attenuated by GB as indicated by immunohistochemical and PCR analysis. Furthermore, CCl-mediated increases in the inflammatory factors tumor necrosis factor-alpha and interleukin-1β secretion into the serum and their expression in liver tissues were reversed following GB treatment, as revealed by ELISA and PCR, respectively. These findings suggested that GB protects against CCl-induced hepatic injury, inflammation and oxidative damage in rats and may be useful in future clinical application of liver injury and disease.
肝损伤可由多种损伤因素引起，包括肝炎以及酒精、药物和其他毒素所致的化学毒性。本研究在四氯化碳（CCl₄）诱导的肝损伤大鼠模型中评估了中药片仔癀肝宝（GB）的保肝作用及其潜在作用机制。将60只雄性Sprague-Dawley大鼠随机分为6组：i）对照组；ii）CCl₄损伤模型组；iii）水飞蓟宾作为阳性药物对照组；iv）150 mg/kg GB组；v）300 mg/kg GB组；vi）600 mg/kg GB组。对照组大鼠不接受任何处理，其余大鼠腹腔注射CCl₄（2 ml/kg）以诱导急性肝病。在各治疗组中，于CCl₄处理前口服给予水飞蓟宾或GB，持续7天。在注射CCl₄后24小时处死动物。结果显示，GB显著降低了CCl₄诱导的血清中天冬氨酸转氨酶、丙氨酸转氨酶、碱性磷酸酶、γ-谷氨酰转肽酶和总胆红素水平。组织病理学分析表明，GB还可防止CCl₄诱导的肝组织变化。GB处理可抑制CCl₄诱导的肝脏内源性抗氧化酶超氧化物歧化酶、谷胱甘肽和谷胱甘肽过氧化物酶活性降低，以及丙二醛和硫代巴比妥酸反应性物质增加。免疫组织化学和PCR分析表明，CCl₄还可使肝组织中活化的NF-κB显著增加，而GB可使其减弱。此外，ELISA和PCR结果分别显示，GB处理后可逆转CCl₄介导的血清中炎症因子肿瘤坏死因子-α和白细胞介素-1β分泌增加以及它们在肝组织中的表达增加。这些结果表明，GB可保护大鼠免受CCl₄诱导的肝损伤、炎症和氧化损伤，可能对未来肝损伤和疾病的临床应用具有一定价值。
