探討小檗鹼調控肝臟脂肪代謝機制

Abstract

全球人類在日漸過重以及肥胖的趨勢之下，非酒精性脂肪肝已經成為了普遍的肝臟疾病之一。從廣泛的定義來說，當肝臟細胞中以三酸甘油脂為主要成份組成的脂肪累積重量超出了細胞總重量的百分之五時，就稱為非酒精性脂肪肝。非酒精性脂肪肝的疾病演變從初期細胞內病態性的脂肪與油滴累積，造成不同程度的發炎導致肝臟發炎與纖維化，在臨床病理學上肝纖維化會進一步惡化成肝硬化、肝癌、肝機能受損且伴隨著極高的死亡風險。然而，由於目前並無標準藥物亦沒有專一性的治療方法可以逆轉脂肪肝的發生。現今揭開肝臟中脂肪堆積的過程和預防脂肪肝的產生，已成為科學家的研究的課題。 小檗鹼是一種可以從諸多藥用植物如黃連中萃取出的異喹啉類生物鹼，具有廣泛的藥用效果:抗癌、抗菌、抗發炎與保肝。自從指出小檗鹼為新的降膽固醇藥物，研究小檗鹼與膽固醇、脂肪代謝是有趣且重要議題。更有研究相繼指出小檗鹼具有降血糖、降血脂與降低密度膽固醇的功能，甚者在動物實驗中的證據也說明了小檗鹼可以降低肝臟中的脂肪含量。

Nonalchoholic fatty liver disease (NAFLD) is rapidly becoming one of the most common liver disease because of growing prevalence of overweight and obesity. NAFLD is defined by fat accumulation, mainly triglycerides, in hepatocytes exceeding 5% of its weight. The term NAFLD includes a wide spectrum of liver abnormalities from simple steatosis, with intrahepatic lipid accumulation and growth of lipid droplets, to nonalcoholic steatohepatitis (NASH), with different degrees of inflammation and fibrosis. As the clinical pathologic spectrum, NASH may progress from steatohepatitis, to advanced cirrhosis, hepatocellular carcinoma, hepatic decompensation, and have increased all-cause mortality. Because of there are no standard drug treatment or specific therapy to reverse fatty liver disease. Nowadays, researchers are ongoing to uncover what processes may trigger fat build-up in the liver and how to prevent and treat the fatty liver disease. Berberine (BBR), an isoquinoline alkaloid isolated from many medicinal herbs such as Coptidis Rhizoma, has a wide range of pharmacological effects. Previous studies have found that pharmacological effects including anti-cancer, anti-microbial, anti-inflammatory, and hepatoprotective effects. Since BBR has been reported as a novel cholesterol lowing drug, recent studies have focused on cholesterol and lipid metabolism related pharmacological effects of berberine. Some reports have shown that berberine has hypoglycemic, hypolipidemic and LDL-lowing effects. Increasingly evidences prove that berberine reduces the liver fat content in vivo, however, the detailed molecular mechanisms have not been systemic elucidated.