摘要: | 本研究第一階段以四氯化碳誘導大鼠急性肝炎動物模式,探討五種清熱藥--秦皮(Fraxini Cortex)、知母(Anemarrhenae Rhizoma)、地榆(Sanguisorbae Radix)、地骨皮(Lycii Chinense Cortex)與翻白草(Potentillae Discoloris Herba)之 乙醇粗抽物對於四氯化碳誘導急性肝損傷之肝保護作用。評估指標包括-- 肝功能試驗相關之血清生化值(GOT、GPT)檢測、肝臟中抗氧化酵素catalase、superoxide dismutase(SOD)、glutathione reductase (GR)、glutathione peroxidase(GPx)測定。
結果顯示口服五種清熱藥對於四氯化碳引起GOT、GPT升高現象,具有顯著的降低作用。抗氧化酵素方面,秦皮可提升catalase、GR、SOD、GPx酵素活性,其他清熱藥可亦提升抗氧化酵素性。由以上結果顯示,秦皮保肝效果最顯著。
第二階段以氯化碳誘導大鼠慢性肝損傷八週模式,探討秦皮乙醇粗抽物及其成分esculetin之功效及作用機轉。功效評估指標包括血清GOT、GPT、TG、total cholsterol及肝臟抗氧化酵素(catalase、SOD、GPx、GR)、nitrite oxide(NO)與細胞轉化因子(transforming growth factor-β1; TGF-β1)之檢測。
結果發現秦皮(1.0 /kg)及其成分esculetin(500 mg/kg)明顯降低血清GOT、GPT值、增加SOD、GPx、GR之活性、降低肝臟NO及TGF-β1含量。肝臟組織切片圖可發現秦皮及其成分esculetin,可降低四氯化碳對大鼠誘發之肝細胞腫脹、淋巴球浸潤、細胞空泡化、肝細胞壞死及結締組織增生之情況。
綜合以上結果,五種清熱藥對於急性肝損傷皆具有保護作用,但以秦皮效果最顯著,其作用機轉可能與提升抗氧化酵素活性有關。秦皮(1.0 g/kg)及其成分esculetin(500 mg/kg)對於慢性肝損傷保護作用最顯著,其機轉可能與提升抗氧化酵素活性、降低肝臟NO含量與降低TGF-β1之含量有關。
At the first stage of this study we investigate the effects of five heat-clearing drugs (Fraxini Cortex, Anemarrhenae Rhizoma, Sanguisorbae Radix, Lycii Chinense Cortex and Potentillae Discoloris Herba) on the carbon tetrachloride (CCl4)-induced experimental hepatic damage in rats were investigated. The hepatoprotective activity of five heat-clearing drugs was evaluated by measuring the activities of serum marker enzymes like serum glutamate oxaloacetate transaminase (sGOT),glutamate pyruvate transaminase (sGPT),and antioxidant enzymes superoxide dismutase (SOD),catalase, glutathione peroxides (GPx), glutathione reductase (GR). The results shown that the five-clearing drugs possessed a significant protective effect by lowering the serum GOT and GPT. Fraxini Cortex significant increased catalase, SOD, GPx and GRx activities,the most effective in hepatoprotection was Fraxini Cortex.
In the second stage, the effect of Fraxini Cortex and esculetin on the CCl4 induced chronic liver damage was investigated.The hepatoprotective activity of Fraxini Cortex and esculetin was evaluated by measuring the activities of serum marker (sGOT, sGPT), the levels of TG and cholesterol, the activities of antioxidant enzymes( catalase, SOD, GR, GPx), and nitrite oxide (NO)and transforming growth factor-β1. (TGF-β1). The result shown that, Fraxini Cortex (1.0g/kg) and esculetin (500mg/kg) significantly by lowering the sGOT and sGPT. Fraxini Cortex (1.0g/kg) and esculetin (500mg/kg) significant increased the activities of catalase, SOD, GPx and GR. By the way, Fraxini Cortex and esculetin (500mg/kg) decreased in the levels of nitrite oxide and TGF-β1.Histopathological study showed that Fraxini Cortex and esculetin reduced the incidence of liver lesions including hepatic cells cloudy swelling, lymphocytes infiltration, cytoplasm vacuolization hepatic necrosis and fibrous connective tissue proliferated induced by CCl4 in rats.
Generally, the five heat-clearing drugs possessed hepatoprotective effect against CCl4-induced acute liver injury. Fraxini Cortex(1.0g/kg) and esculetin (500mg/kg) can counteract the acute or chronic liver injury through activated antioxidant enzymes and decreaed of nitrite oxide and TGF-β1 levels. |