Hubbard Ruth E, O'Mahony M Sinead, Calver Brian L, Woodhouse Ken W
Department of Geriatric Medicine, School of Medicine, Cardiff University, 3rd Floor, Academic Centre, Llandough Hospital, Penarth, UK.
Eur J Clin Pharmacol. 2008 Sep;64(9):895-900. doi: 10.1007/s00228-008-0499-1. Epub 2008 May 28.
Esterases are enzymes of drug metabolism known to be reduced in frail older people and during acute illness. The mechanism for this is unknown. The aim of this study was to examine esterase activity and inflammation in ageing and frailty.
Thirty frail patients (mean age 84.9 years) dependent on continuing inpatient care, 40 patients of intermediate frailty attending Day Hospital (84.2 years), 40 fit older controls (82.7 years) and 30 young controls (23.3 years) were studied. Frailty indicators, plasma esterase activities and markers of inflammation were measured.
With increasing patient frailty, C-reactive protein (CRP), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) increased significantly and esterase activity, with the exception of aspirin esterase, fell significantly (p < 0.005). There were significant negative correlations between log-transformed IL-6 and acetylcholinesterase (r = -0.354, p < 0.01), butyrylcholinesterase (r = -0.392, p < 0.01) and benzoylcholinesterase activity (r = -0.241, p < 0.05) and significant negative correlations between TNF-alpha and acetylcholinesterase (r = -0.223, p < 0.01), butyrylcholinesterase (r = -0.279, p < 0.01) and benzoylcholinesterase activity (r = -0.253, p < 0.01). Aspirin esterase activity did not correlate with IL-6 or TNF- alpha.
Frailty was associated with higher inflammatory markers and lower esterase activity. There was a weak but significant negative correlation between both IL-6 and TNF-alpha and the activity of three of four esterases. The negative correlation between esterase activity and inflammatory markers may have a causal basis, comparable to the inflammatory suppression of cytochrome P-450 enzymes.
酯酶是药物代谢酶,已知在体弱的老年人和急性疾病期间其活性会降低。其机制尚不清楚。本研究的目的是研究衰老和体弱过程中的酯酶活性及炎症情况。
对30名依赖持续住院护理的体弱患者(平均年龄84.9岁)、40名日间医院就诊的中度体弱患者(84.2岁)、40名健康老年对照者(82.7岁)和30名年轻对照者(23.3岁)进行了研究。测量了体弱指标、血浆酯酶活性和炎症标志物。
随着患者体弱程度增加,C反应蛋白(CRP)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)显著升高,除阿司匹林酯酶外,酯酶活性显著下降(p<0.005)。对数转换后的IL-6与乙酰胆碱酯酶(r = -0.354,p<0.01)、丁酰胆碱酯酶(r = -0.392,p<0.01)和苯甲酰胆碱酯酶活性(r = -0.241,p<0.05)之间存在显著负相关,TNF-α与乙酰胆碱酯酶(r = -0.223,p<0.01)、丁酰胆碱酯酶(r = -0.279,p<0.01)和苯甲酰胆碱酯酶活性(r = -0.253,p<0.01)之间也存在显著负相关。阿司匹林酯酶活性与IL-6或TNF-α无相关性。
体弱与较高的炎症标志物和较低的酯酶活性相关。IL-6和TNF-α与四种酯酶中的三种活性之间存在微弱但显著的负相关。酯酶活性与炎症标志物之间的负相关可能有因果关系,类似于细胞色素P-450酶的炎症抑制作用。