天然物之護肝功能評估 第一部分：杜莎藻對四氯化碳誘發小鼠肝損傷的保護作用探討 第二部分：沙棘仔油對四氯化碳誘發小鼠肝損傷的保護作用探討

Hepatoprotective of natural products : Part I: Protective effects of Dunaliella salina — A carotenoids-rich alga, against carbon tetrachloride-induced hepatotoxicity in mice Part II: Protective effects of seabuckthorn (Hippophae rhamnoides L.) seed oil against carbon tetrachloride-induced hepatotoxicity in mice

許又文(Yu-Wen Hsu)

指導教授 ： 呂鋒洲

中山醫學大學/醫學院/醫學研究所/博士(2009年)

https://doi.org/10.6834/CSMU.2009.00066

摘要

第一部分
本實驗的目的在探討杜莎藻對四氯化碳誘發小鼠肝損傷的保護功效。實驗共分為六組，含正常飲食組(控制組)、四氯化碳負對照組、Silymarin正對照組及三個添加不同劑量之杜莎藻實驗組（71 mg/kg、355 mg/kg、710 mg/kg）。除正常飲食組外，其餘每組每週於星期二和星期四投予兩次四氯化碳(20%, 0.1 ml/mice)連續八週。不同劑量杜莎藻組每週餵食五次，分別於星期二、三、四、五、六餵食不同劑量之杜莎藻。Silymarin對照組餵食時間與杜莎藻組相同，餵食Silymarin (200 mg / kg)每週五次。評估指標包括小鼠體重和臟器重量比較、肝功能試驗相關之血液生化值(AST、ALT、ALP、TG和Cholesterol)及肝組織抗氧化指標(GSH、GSH-Rd、GSH-Px、catalase、SOD、MDA-TBA)。實驗結果顯示餵食不同劑量杜莎藻的實驗組之ALT，AST，TG和cholesterol均明顯(p < 0.05)比四氯化碳組低；杜莎藻可顯著(p < 0.05)提高肝臟組織中抗氧化酵素的活性(GSH-Px，GSH-Rd，SOD，catalase)及增加GSH的含量，同時也具有顯著(p < 0.05)降低四氯化碳引起肝臟之脂質過氧化的傷害(MDA-TBA)；在組織切片觀察上，杜莎藻組小鼠的肝臟組織病變及肝纖維化程度均明顯比四氯化碳組輕微(p < 0.05)。Silymarin正對照組所呈現之結果與杜莎藻組相似。由這些結果顯示，杜莎藻具有保護四氯化碳所誘發之小鼠肝損傷之能力。杜莎藻保護肝臟之作用可能是經由提高肝臟組織中的抗氧化酵素及降低肝臟中脂質過氧化的傷害。
第二部分
本實驗的目的在探討沙棘籽油對四氯化碳誘發小鼠肝損傷的保護功效。實驗共分為七組，含正常飲食組(控制組)、橄欖油控制組、四氯化碳負對照組、Silymarin正對照組及三個添加不同劑量之沙棘籽油實驗組（0.26, 1.30, and 2.60 mg/kg）。除正常飲食組外，其餘每組每週於星期二和星期四投予兩次四氯化碳(20%, 0.1 ml/mice)連續八週。不同劑量沙棘籽油組每週餵食五次，分別於星期二、三、四、五、六餵食不同劑量之沙棘籽油。Silymarin對照組餵食時間與沙棘籽油相同，餵食Silymarin (200 mg / kg)每週五次。評估指標包括小鼠體重和臟器重量比較、肝功能試驗相關之血液生化值(AST、ALT、SALP、total protein、total albumin、TG和Cholesterol)及肝組織抗氧化指標(GSH、GSH-Rd、GSH-Px、catalase、SOD、MDA-TBA)。實驗結果顯示餵食不同劑量沙棘籽油的實驗組之ALT，AST，TG和cholesterol均明顯(p < 0.05)比四氯化碳組低；沙棘籽油可顯著(p < 0.05)提高肝臟組織中抗氧化酵素的活性(GSH-Px，GSH-Rd，SOD，catalase)及增加GSH的含量，同時也具有顯著降低四氯化碳引起肝臟之脂質過氧化的傷害(MDA-TBA)；在組織切片觀察上，沙棘籽油組小鼠的肝臟組織病變及肝纖維化程度均明顯比四氯化碳組輕微(p < 0.05)。Silymarin正對照組所呈現之結果與沙棘籽油組相似。由這些結果顯示，沙棘籽油具有保護四氯化碳所誘發之小鼠肝損傷之能力。沙棘籽油保護肝臟之作用可能是經由提高肝臟組織中的抗氧化酵素及降低肝臟中脂質過氧化的傷害。

關鍵字

杜莎藻 ； 沙棘籽油 ； 護肝 ； 四氯化碳 ； 脂質過氧化 ； 抗氧化酵素

並列摘要

Part I
The protective effects of Dunaliella salina (D. salina) on liver damage were evaluated by carbon tetrachloride (CCl4)-induced hepatotoxicity in mice. Male ICR mice were orally treated with D. salina or silymairn daily with administration of CCl4 twice a week for 8 weeks. CCl4 induced liver damage and significantly (p < 0.05) increased the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) in serum and decreased the activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px), and GSH content in liver whereas increased hepatic malondialdehyde (MDA) content as compared with control group. Treatment with D. salina or silymarin could significantly (p < 0.05) decrease the ALT, AST, and ALP levels in serum and increase the activities of SOD, catalase, GSH-Px, glutathione reductase, and GSH content and decrease the MDA content in liver when compared with CCl4-treated group. Liver histopathology also showed that D. salina reduced the incidence of liver lesions induced by CCl4. The results suggest that D. salina exhibits potent hepatoprotective effects on CCl4-induced liver damages in mice, and that the hepatoprotective effects of D. salina may be due to both the increase of antioxidant enzymes activities and inhibition of lipid peroxidation.
Part II
The present study examined the protective effects of seabuckthorn (Hippophae rhamnoides L., SBT) seed oil on carbon tetrachloride (CCl4)-induced hepatic damage in male ICR mice. Our results showed that oral administration of SBT seed oil at doses of 0.26, 1.30, and 2.60 mg/kg for 8 weeks significantly reduced the elevated levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), triglyceride (TG) and cholesterol at least 13% in serum, and the level of malondialdehyde (MDA) in liver at least 22%, that was induced by CCl4 (1 ml/kg) in mice. Moreover, the treatment of SBT seed oil was also found to significantly increase the activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px), glutathione reductase (GSH-Rd) and GSH content in liver up to 134%. Our study found that the optimal dose of SBT seed oil was 0.26 mg/kg, as the minimum amount exhibiting the greatest hepatoprotective effects on CCl4-induced liver injury. Overall, the hepatoprotective effect of SBT seed oil at all tested doses was found to be comparable to that of silymarin (200 mg/kg) and have been supported by the evaluation of the liver histopathology in mice.

並列關鍵字

Dunaliella salina ； seabuckthorn seed oil ； hepatoprotective ； carbon tetrachloride (CCl4) ； lipid peroxidation ； antioxidant enzymes

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