輔酶Q10與冠狀動脈心臟病人的抗氧化能力及發炎狀態的關係

台灣衛生署公告101年國人死亡原因心臟、腦血管及高血壓等心血管疾病在十大死因中，為第2位僅次於惡性腫瘤。已知造成心血管疾病的原因主要來自血管的病變和動脈粥狀硬化，嚴重時會引發血管狹窄、缺血，續引發冠狀動脈心臟病（coronary artery disease; CAD）、心臟衰竭、中風等致死等的併發症。動脈粥狀硬化為CAD主要成因，形成過程複雜，其致病機轉涉及脂質代謝異常、氧化壓力及炎症反應。因此預防及治療動脈粥狀硬化為醫療上很重要的議題。輔酶Q10（coenzyme Q10 亦稱為Ubiquinone）為一種內生性親脂溶性的抗氧化物質，是參與粒線體氧化磷酸反應及電子傳遞鏈（electron transport chain）產生能量－ATP之必須輔助因子（essential cofactor）。已有臨床實驗證實對罹患高血壓、心臟衰竭及心臟手術病人，使用補充輔酶Q10可以顯著改善其心臟功能， 增進運動耐受性及縮短手術後恢復時間。本研究探討CAD之病人其抗氧化活性、發炎狀態與輔酶Q10血中濃度之關係，輔酶Q10濃度與罹患CAD之相關性，並接受高劑量輔酶Q10補充劑後，對於抗氧化酵素活性與發炎反應之效應。以期提供積極預防及治療CAD之依循。此研究共募集51位CAD病人及102位健康受試者，測量其血壓、血中脂質、脂質過氧化物（MDA丙二醛）、抗氧化酵素 [ 超氧化物歧化酶( SOD )、過氧化氫酶( CAT )及麩胱甘肽過氧化酶 (GPx）] 活性與發炎指標[ 超敏感C-反應性蛋白腫( hs-CRP )、介白素-6 ( IL-6）、同半胱胺酸]。追蹤51位CAD病人受試者接受隨機分派後，分別給予輔酶Q10補充劑 (60mg/天，n = 19) 或高輔酶Q10補充劑(150mg/天，n = 18)，持續3個月。結果顯示CAD病人之輔酶Q10、CAT、SOD、GPx濃度皆比健康受試者有顯著下降，MDA濃度顯著高於健康受試者。但調整CAD 危險因子後，SOD 活性對血漿輔酶Q10濃度有顯著之負相關性。當血漿輔酶Q10(≧0.52 μM)時會顯著降低罹患CAD 之危險對比值( OR, 0.08; 95% CI,0.02-0.36)。完成研究43位CAD之受試者，在輔酶Q10補充劑組（150 mg/d）之血漿輔酶Q10濃度於第4週起持續顯著上升 (P < 0.01）。在第8週MDA濃度有顯著降低(P = 0.03）。在第12週CAT、SOD濃度有顯著上升（P = 0.03；SOD，P = 0.03），及IL-6濃度顯著降低（P = 0.03）。同時輔酶Q10與GPx和同型半胱氨酸之間無相關性。此研究結果顯示血漿輔酶Q10≧0.52 μM 可顯著降低罹患CAD 之風險，高劑量的輔酶Q10補充劑（150毫克/天）介入可以減少CAD病人的MDA濃度和提高SOD、CAT活性， 並減少發炎指標IL-6。因此高劑量的輔酶Q10補充劑可促進CAD病人者的抗氧化與抗發炎等反應。

According to the statistics of Department of Health, R.O.C. (TAIWAN), cardiovascular disease rate of the standardized mortality, has been the second cause-of-death behind cancer among the top 10 in 2012. Cardiovascular disease (CVD) including coronary artery disease (CAD), congestive heart failure, cardiomyopathy, stroke and other fatal complications. Atherosclerosis is the main cause of CAD, The pathogenesis of atherosclerosis involves a complex series of events, as abnormal lipid metabolism, oxidative stress and chronic inflammatory process, with the formation of atherosclerotic plaque as the end result. Therefore the prevention and treatment of atherosclerosis is important topics in medical healthcare.Coenzyme Q10 (ubiquinone) is a lipid-soluble anti-oxidant with cell protective effect, also plays as an essential cofactor in mitochondrial oxidative phosphorylation and ATP production. In clinical trial, the supplementation of Q10 as an adjunct to conventional therapy in patients with congestive heart failure, cardiomyopathy and ishemic cardiac surgery shows that it can afford significant clinical benefit in exercise tolerance, heart function and reducing recovery period.The aim of this study was to investigate the relationship of antioxidant enzyme activities and inflammatory status with CQ10 concentration in patient with coronary artery disease, and calculate the odds ratio of coronary artery disease with the CQ10 concentration. Furthermore, this study was to investigate the effects of CoQ10 supplementation in response to antioxidant enzyme activity and inflammatory status in patients with coronary artery disease. Patient who were identified by cardiac catheterization as having at least 50% stenosis of one major coronary artery were assigned to case group (n = 51) and healthy participated was assigned to the control group (n = 102) in this study. Hematologic profiles, plasma CoQ10, malondialdehyde (MDA), antioxidant enzyme activity: superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) and inflammatory markers [ High-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6) and homcysterine] were measured. Fitty-one subjects with CAD (47 males/ 4 females) were randomly assigned to one of three groups: a placebo group (n = 14), or one of two CoQ10 groups (60 mg/d, n = 19 [Q10-60] group; 150 mg/d, n = 18 [Q10-150]) group] and intervention for 12 weeks. Forty-three subjects with CAD completed the intervention study. The result showed that CoQ10 concentration, CAT, SOD and GPx enzyme activities were significantly lower than healthy participants, MDA was significantly higher than healthy participant. The Plasma Q10 concentration and SOD had statistically significant negative correlation after adjusted CAD confounders. Plasma Q10 concentration (≧0.52 μM) had a significant association with decreased risk of CAD (OR, 0.08; 95% CI, 0.02-0.36). After 12 week of Q10 supplementation, the results show plasma CoQ10 concentration were significantly increased after supplementation in the Q10-150 group (P < 0.01) at week 4. The MDA levels were significantly lower than placebo at week 8 (P = 0.03). At the week 12, the antioxidant enzyme activities of CAT (P = 0.03) and SOD (P = 0.03) were significantly higher than placebo but also the inflammatory marker IL-6 (P = 0.03) were significantly lower than the placebo, too. However, there was not relationship between CoQ10 concentration and GPx activity or homocysteine. In conclusion, Plasma Q10 concentration (≧0.52 μM) had a significantly association with lower risk of CAD. In addition, high dose of CoQ10 supplementation ( 150 mg / day) intervention have a significantly increase CoQ10 concentration and anti-oxidant enzyme activities (SOD, CAT ) and have a significantly lower MDA and IL-6 concentration, Therefore higher dosage of Q10 supplementation may benefit patients with CAD by anti-oxidative and anti-inflammatory activities.