| 摘要: | 非酒精性脂肪肝疾病(Non-Alcoholic Fatty Liver Diseases, NAFLD)在全球及台灣盛行率逐漸增加，許多研究表示腸道損傷在NAFLD之疾病發展也扮演關鍵角色。米麴(rice koji)是米經Aspergillus Oryzae發酵之產物，經研究發現對於高血糖、高血脂等具有改善的效果，並且含有較多的γ-胺基丁酸 (gamma-Aminobutyric acid, GABA)。經研究表示GABA具有改善代謝疾病的效果，因此推斷GABA可能具有改善NAFLD之潛力。本實驗將由Aspergillus Oryzae發酵之米麴與具有GABA之乳酸菌發酵液共同培養所得之高GABA含量米麴粉末(GABA-enriched koji powder, GK)介入以高脂飼料(high fat diet) 誘導NAFLD之大鼠，並以腸肝軸之觀點探討其對於NAFLD之改善效果。本實驗為期8週，飼養36隻Sprague Dawley(SD)雄性6週齡大鼠，經1週飼養期後，隨機分為6組，分別為正常飼料對照組(normal control diet, NC)、正常飼料GK低劑量組(NCLGK)、正常飼料GK高劑量組(NCHGK)、高脂飼料組(HF)、高脂飼料 GK低劑量組(HFLGK)以及高脂飼料GK高劑量組(HFHGK)，每週換食三次，且每週紀錄體重兩次。實驗於第8週進行犧牲，將樣品收集後進行肝臟氧化壓力、肝臟發炎反應指標、肝臟脂質代謝相關蛋白質表現與mRNA含量、脂肪組織發炎反應指標、胰島素阻抗、腸道通透性、腸道菌相分佈以及短鏈脂肪酸含量之分析。SD大鼠經實驗期8週後相較正常飼料之組別，高脂飼料之組別體重、肝臟NAFLD score與氧化壓力指標顯著增加，另外，腸道菌相分佈改變，而高GABA含量米麴粉末可能透過改變腸道菌相組成影響代謝物而改善肝臟內脂質堆積，表示高GABA含量米麴粉末對於NAFLD之改善效果仍具有一定潛力。
Non-Alcoholic Fatty Liver Disease (NAFLD) is becoming increasingly prevalent both globally and in Taiwan. Many studies suggest that intestinal damage plays a crucial role in the development of NAFLD. Rice koji is a product fermented by Aspergillus Oryzae, and research has found that it has beneficial effects on hyperglycemia and hyperlipidemia, and it contains a higher amount of γ-Aminobutyric acid (GABA). Studies indicate that GABA has the potential to improve metabolic diseases, leading to the hypothesis that GABA might have the potential to ameliorate NAFLD. In this experiment, the GABA-enriched koji powder (GK), obtained from co-culturing rice koji fermented by Aspergillus Oryzae and GABA-producing lactic acid bacteria fermentation broth, will be used to intervene in NAFLD induced by a high-fat diet in rats. The study will explore its effects on NAFLD from the perspective of the gut-liver axis. This 8-week experiment will involve 36 six-week-old male Sprague Dawley (SD) rats. After a one-week feeding period, the rats will be randomly divided into six groups: normal control diet (NC), normal control diet with low dose GK (NCLGK), normal control diet with high dose GK (NCHGK), high-fat diet (HF), high-fat diet with low dose GK (HFLGK), and high-fat diet with high dose GK (HFHGK). Food will be changed three times a week, and body weight will be recorded twice a week. At the end of the 8th week, samples will be collected to analyze liver oxidative stress, liver inflammatory cytokines, liver lipid metabolism-related protein expression and mRNA levels, adipose tissue inflammatory cytokines, insulin resistance, intestinal permeability, gut microbiota distribution, and short-chain fatty acid (SCFA) content. After the 8-week experimental period, compared to the normal control diet groups, the high-fat diet groups showed significant increases in body weight, hepatic NAFLD score, and oxidative stress. Additionally, gut microbiota distribution was altered. The GABA-enriched koji powder might ameliorate liver lipid accumulation by altering gut microbiota composition and influencing metabolites, suggesting that GABA-enriched koji powder still holds potential for improving NAFLD. |
