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低劑量粒線體抑制劑對於非酒精性脂肪肝疾病形成之影響

低劑量粒線體抑制劑對於非酒精性脂肪肝疾病形成之影響.

charissa-boone
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低劑量粒線體抑制劑對於非酒精性脂肪肝疾病形成之影響

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  1. 低劑量粒線體抑制劑對於非酒精性脂肪肝疾病形成之影響低劑量粒線體抑制劑對於非酒精性脂肪肝疾病形成之影響 • 非酒精性脂肪肝疾病 (nonalcoholic fatty liver disease, NAFLD) 包含單純脂肪變性、肝炎 (nonalcoholic steatohepatitis, NASH) 、纖維化、壞死及硬化之肝傷害。NASH進展過程還未完全明瞭，其病理進展有二次傷害假說，主要指胰島素抗性與氧化性傷害，而在這二次傷害假說中，粒線體功能失常可能扮演著重要角色。本次實驗目的主要在瞭解低劑量粒線體抑制劑對於非酒精性脂肪肝疾病形成之影響。以雄性Sprague Dawley (SD) 大鼠隨機分成五組，餵食AIN-93飲食或能量百分比為59%高脂飲食予以自由攝取。另以粒線體抑制劑rotenone (0.51 μmol) 經腹腔每週三次給予，以誘發粒線體功能失常之實驗模式。14週高脂飲食介入後無論是否給予rotenone，皆發展為脂肪肝，其肝臟中三酸甘油酯、總膽固醇及游離脂肪酸顯著高於控制組 (p<0.05)，但血漿中三酸甘油酯濃度則相反 (p<0.05)。肝臟硫代巴比妥酸反應物質於五組中皆無顯著差異。另外，肝臟腫瘤壞死因子-α則顯著低於控制組 (p<0.05)。餵食大鼠59%高脂飲食有無介入rotenone之組別其琥珀酸細胞色素c還原酶活性顯著高於其他組別 (p<0.05)。此外，高脂飲食介入生理食鹽水或rotenoen之大鼠肝臟中粒線體DNA套數皆高於餵食AIN-93M飲食之大鼠，但於大鼠肝臟細胞核DNA轉錄轉譯之flavoprotein蛋白質表現以及粒線體DNA轉錄轉譯之cytochrme c oxidase subunit II蛋白質表現量於四組間無顯著差異 (p<0.05)。本實驗結果顯示，餵食高脂飲食合併介入rotenone之大鼠已誘導為單純脂肪肝，但無誘導為非酒精性脂肪肝炎 (NASH)。 因此推測，低劑量粒線體抑制劑無法加速NAFLD之進程。

  2. Effect of Low Concentration of Mitochondrial Inhibitor on Nonalcoholic Fatty Liver Disease • Nonalcoholic fatty liver disease (NAFLD) includes simple steatosis, steatohepatitis (NASH), fibrosis, necrosis and cirrhosis. Pathogenesis of NASH is still incompletely understood. A double hit hypothesis, insulin resistance and oxidative stress, was proposed for the development of NASH. Mitochondrial dysfunction may play a central role in NAFLD development. The aim of this study was to determine the relationship between NAFLD and low concentration of mitochondrial inhibitor, rotenone. Male Sprague Dawley (SD) rats were randomly distributed to five groups. Rats fed 59% high fat diet (energy from fat) or AIN-93M diet ad libitum for 14 weeks. Rotenone (0.51 μmol) was given intraperitoneally three times a week. Rats fed high fat diet for 14 weeks developed steatosis. Liver contents of triglyceride (TG), total cholesterol and non-esterified fatty acid in rats fed high fat diet with or without rotenone treatment were higher than rats fed AIN-93M diet (p < 0.05). However, plasma TG concentration showed opposite results (p < 0.05). There was no significantly differences of thiobarbituric acid-reactive-substance (TBARS) between five groups. Tumor necrosis factor-α in rats fed high fat diet with or without rotenone treatment were lower than rats fed AIN-93M diet (p < 0.05). The succinate cytochrome c reductase (SCCR) activity in liver of rats which fed high fat diet with or without rotenone treatment were higher than other groups (p < 0.05). Mitochondrial DNA (mtDNA) copy number in liver of rats which fed high fat diet with normal saline or rotenone was higher than rats fed AIN-93M. Nucleic DNA encode protein, flavoprotein, and mitochondrial DNA encode protein, cytochrme c oxidase subunit II, were not significant differences between four groups. These results showed the high fat diet with low concentration of rotenone treatment may induce simple steatosis but not induce NASH. These studies suggest low mitochondrial inhibitor does not accelerate progression of NAFLD.

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