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紅麴萃取物對Ang II 誘發H9c2心肌母細胞肥大的預防作用
心血管疾病是全球的主要死因之一，而心血管疾病最明顯的後發症之一即是心肌肥厚。心肌肥厚主要是因為高血壓、心肌梗塞、瓣膜性心臟疾病以及擴張型心肌病等因素使心臟長期承受超負荷所導致的。許多研究顯示，心肌肥厚的病理過程是經由腎素-血管緊張素系統 (rennin-angiotensin system, RAS) 促使活性氧自由基 (reactive oxygen species, ROS) 的生成增加所致。血管收縮II (angiotensin II, Ang II) 是RAS的主要胜肽，Ang II會使nicotinamide adenine dinucleotide phosphate (NADPH) 氧化酶活性增加，進而啟動絲裂原活化蛋白激 (mitogen activated protein kinase, MAPK) 導致心肌肥厚。近幾年紅麴米 (red mold rice, RMR) 成為一種熱門的保健食品，RMR主要是使用紅麴菌 (Monascus species) 以米為發酵基質所製得，在亞洲應用已有數千年，主要用以提高食物的顏色和味道。RMR中monacolin K (MK)、monascin (MS)、總酚及黃酮類化合物，被認定具有抗氧化，降低膽固醇和預防癌症的效果。RMR-E降低膽固醇的作用主要是MK，也稱為洛伐他汀 (lovastatin, LOV)。我們的研究目在探討紅麴萃取物 (RMR-E) 對Ang II誘發H9c2心肌母細胞肥厚的預防作用。我們在H9c2心肌母細胞中事先給予RMR-E、MS及LOV，再添加Ang II誘發，測定RMR-E、MS、LOV對心肌肥厚的抑制作用。我們使用MTT assay、Bradford assay、流式細胞儀、DCF assay及西方墨點法檢測細胞的存活率、細胞大小、蛋白質濃度、ROS 的含量及MAPKs (JNK, ERK1/2和P38) 蛋白表現。我們發現H9c2心肌母細胞對RMR-E可承受的濃度為75 慊/mL。結果顯示，RMR-E (75 μg/mL) 會降低Ang II誘發H9c2心肌母細胞肥厚的蛋白質含量，也會減少ROS的產生以及減少MAPKs活化。結論是RMR-E能經由減少細胞內ROS及MAPKs來抑制Ang II所誘發H9c2心肌母細胞的肥大。
Cardiovascular diseases are the leading cause of death worldwide. Cardiac hypertrophy is one of the most significant sequelae of cardiovascular diseases which is the principal response of the heart to overload from any cause, including hypertension, myocardial infarction, valvar heart disease, and dilated cardiomyopathy. Numerous studies have shown that generation of reactive oxygen species (ROS) induced by the renin-angiotensin system (RAS) is involved in this hypertrophy pathological process. Angiotensin II (Ang II) is considered the main effector peptide of the RAS. Ang II induced hypertrophy is mediated via NADPH oxidase activation through MAPKs activation. In recent years, red mold rice (RMR) products become a popular health supplement, RMR is prepared by Monascus species with rice as their fermentation substrate and used in Asian to enhance food color and flavor for centuries. RMR contain monacolin K (MK), monascin (MS), total phenols, and flavonoids and considered to have antioxidation, lower cholesterol and cancer prevention effects. The cholesterol-lowering effect of RMR is thought to be due to Monacolin K, also known as Lovastatin. The aim of our study investigates the prevents effect of Red mold rice extract (RMR-E) on Ang II induced cardiac hypertrophy in H9c2 cells. We divide H9c2 cells into five groups (control, Ang II , RMR-E, MS and LOV). We pretreat with RMR-E, MS and LOV in H9c2 cells and then add Ang II to detect resistance of cardiac hypertrophy. We use MTT assay, Bradford assay, flow cytometry, DCF assay and Western bolt to detect cell viability, cell size, protein concentration, intracellular reactive oxygen species (ROS) and MAPKs protein (JNK, ERK, and P38) expression level. We find that H9c2 cells can tolerance RMR-E concentraction reach to 75 g/mL. Results showed that RMR-E (75 /mL) show obvious total protein downregulation and significantly attenuate ROS generate and reduce MAPKs activity in Ang II-induced H9c2 cells hypertrophy. In conclusion, RMR-E attenuated Ang II-induced H9c2 cardiomyoblast cells hypertrophy via decreasing intracellular ROS levels and MAPKs expression.