回復尋常飲食比低劑量銀杏葉萃取物對大白鼠非酒精性脂肪肝炎的進展更具有抑制效果

Return to ordinary diet has a better inhibition than low dose of Ginkgo biloba extract on the progression ofnon-alcoholic steatohepatitis in rat

陳 永 發(Yung-Fa Chen)

指導教授 ： 陳盛煊

臺北醫學大學/醫學院/臨床醫學研究所/碩士(2010年)

https://doi.org/10.6831/TMU.2010.00239

摘要

非酒精性脂肪肝病（non-alcoholic fatty liver disease, NAFLD）在西方國家盛行率大約10 ~24%，其中約2~3%是以慢性肝炎為表現，文獻指出在5~13年的追蹤中，約三分之一的病患，其肝臟纖維化程度會加劇，最終可能會演變成肝硬化或產生肝癌，目前對於非酒精性脂肪肝炎（non-alcoholic steatohepatitis, NASH）的治療，除減重、運動來減少胰島素抗性外，並無特定療效的藥物。銀杏葉萃取物是保健的中草藥，在以往使用上並無明顯或重大的副作用，近年來發現它具有很強的清除自由基能力及抗氧化能力，所以本研究目的在於觀察銀杏葉萃取物是否對大白鼠非酒精性脂肪肝炎的進展具有預防效果。在餵食雄性Wistar大白鼠十六週液態高油脂飲食，經病理切片證實誘發NASH後，隨機分為三組：繼續液態高油飲食組（H組）、繼續液態高油飲食加銀杏葉萃取物組（HG組）及恢復尋常固型飼料組（N組），再飼養六週後犧牲，銀杏葉萃取物是採腹腔內注射，劑量為每天每公斤體重25毫克。結果發現在生化檢驗方面，HG組與H組相比只有血清三酸甘油酯及血糖為有意義的下降（P<0.05），其餘如肝功能指數、總膽固醇和血清胰島素均無差別。在肝臟生化檢驗方面，除了游離脂肪酸（free fatty acid, FFA）為有意義的下降外（P<0.01），glutathione reductase、 glutathione peroxidase（GPx）、 superoxide dismutase（SOD）、 lipid peroxidation、myeloperoxidase及tumor necrosis factor-α (TNF-α)也均無差別。另外血清TNF-α、hyaluronic acid及FFA雖有下降的趨勢，但其差別無達到統計上的意義。最後病理組織結果顯示所有HG組其NAS ( NAFLD activity score )都大於或等於五分，持續NASH的病理診斷。相反的，所有N組其NAS都小於五分，病理組織顯示脂肪堆積（P<0.01）及小葉發炎（P<0.05）與H組相比具有統計意義的下降，其次血糖、血清胰島素、肝臟FFA及血清TNF-α的下降和肝臟GPx、SOD的上昇與H組相比，亦具有統計上的差別（P<0.05）。由研究結果顯示補充六週低劑量的銀杏葉萃取物，無法明顯地減少大白鼠的氧化壓力，連帶著也無法防止大白鼠NASH的持續進展，不過經由減少飲食內脂肪的比例，來達到總熱量攝取的減少，是可以逆轉大白鼠NASH的進展。所以是否改變藥物的投予方式（例如改為口服）或延長給藥期間來增加總劑量，而達到實驗成功，是值得我們再去探討的一個議題，另外經由這實驗也證實了飲食、熱量的控制是改善NASH的首要且有效的措施。

關鍵字

非酒精性脂肪肝炎 ； 銀杏葉萃取物 ； 氧化壓力 ； 動物模式

並列摘要

The prevalence of non-alcoholic fatty liver disease (NAFLD) is about 10~24% in the West. Approximately 2~3% of the presentations about this disease were chronic hepatitis and eventually liver cirrhosis or hepatocellular carcinoma may develop. Because lack of specific efficacy of drugs except weight loss, exercise and improvement of insulin resistance, non-alcoholic steatohepatitis (NASH) will surely become an important issue in the future. Strong free radical scavenging ability and antioxidant capacity of Ginkgo biloba extract（EGb 761）has been found in recent years, so the purpose of this study is to observe whether the EGb 761 has the preventive effect on the progression of NASH. NASH confirmed by liver pathology after liquid high-fat diet feeding 16 weeks, these male Wistar rats were randomly divided and fed as following 3 groups for more 6 weeks : liquid high-fat diet group (H group), liquid high-fat diet plus EGb 761 group ( HG group) and ordinary solid diet group (N group). EGb761 was delivered by intra-peritoneal injection with the daily dose of 25 mg/ kg of body weight. Only serum triglyceride and glucose significantly decreased in HG group compared with H group in blood biochemistry（P<0.05）. Others, including liver function test, total cholesterol and serum insulin had no difference between these 2 groups. Except for a significant decline of hepatic free fatty acid concentration in HG group（P<0.01）, the glutathione reductase, glutathione peroxidase, superoxide dismutase, lipid peroxidation, myeloperoxidase and tumor necrosis factor-α had no difference in the liver biochemistry. Although there was a downward trend about the serum concentration of tumor necrosis factor-α, hyaluronic acid and free fatty acid in HG group compared with H group, they still can not reach significant differences. The liver pathologic results showed that the NAS (NAFLD activity score) was more than or equal to five points in all HG group. On the contrary, the NAS of rats in N group were all less than 5 points. The final results showed that the six-week supplement of low dose of EGb 761 can not significantly reduced oxidative stress and prevent the progression of NASH in rats. But it can be achieved by decreasing total calories intake with less fat content in diet. So it is worthy to investigate how to increase the total dose of EGb 761 by changing the route of delivery or extending the duration of experiment. Meanwhile this study proved that restriction of calories intake should be the first task and the most effective in management of NSAH.

並列關鍵字

non-alcoholic steatohepatitis ； Ginkgo biloba extract ； oxidative stress ； animal model

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