A prostaglandin D2 metabolite is elevated in the urine of Duchenne muscular dystrophy patients and increases further from 8 years old
A prostaglandin D2 metabolite is elevated in the urine of Duchenne muscular dystrophy patients and increases further from 8 years old
复制标题
DOI：
10.1016/j.cca.2013.03.031
复制
发表时间：
2013-08-23
影响因子：
5
通讯作者：
Matsuo, Masafumi
中科院分区：
文献类型：
--
作者：
Nakagawa, Taku;Takeuchi, Atstiko;Matsuo, Masafumi
背景：Duchenne型肌营养不良症(Duchenneydystrophy，DMD)是一种由肌营养不良蛋白缺乏引起的进行性肌肉萎缩性疾病。原发肌营养不良蛋白缺乏症的下游原因尚不清楚。本研究通过检测DMD患者尿液中前列腺素D-2(PGD(2))的主要代谢产物四氢吡喃前列腺素(PGDM)，验证了前列腺素D(2)介导的炎症参与DMD发病机制的假说。方法：采用LC-MS/MS法测定DMD患者和年龄匹配的4~15岁健康对照的第一晨尿中四氢前列腺素DM浓度。结果：79例DMD患者和191例DMD患者的尿四氢前列腺素浓度分别为3.08+/-0.15和6.90+/-0.35 ng/mg肌酐(平均值+/-SE)。DMD患者的平均浓度约为对照组的2.2倍(p<；0.05)。值得注意的是，DMD患者尿中四氢吡喃前列腺素浓度具有时序性变化：7岁前仍高于对照组近1.5倍，但在8岁时显著升高。结论：DMD患者尿中四氢前列腺素浓度明显升高，并随年龄增长而升高。提示PGD(2)介导的炎症反应在DMD的病理过程中起一定作用。(C)2013爱思唯尔B.V.保留所有权利。
Background: Duchenne muscular dystrophy (DMD) is a progressive muscle wasting disease caused by muscle dystrophin deficiency. Downstream of the primary dystrophin deficiency is not well elucidated. Here, the hypothesis that prostaglandin D-2 (PGD(2))-mediated inflammation is involved in the pathology of DMD was examined by measuring tetranor PGDM, a major PGD(2) metabolite, in urine of DMD patients.Methods: We measured tetranor PGDM in urine using LC-MS/MS. First morning urine samples were collected from genetically confirmed DMD patients and age-matched healthy controls aged 4 to 15 y.Results: The urinary tetranor PGDM concentration was 3.08 +/- 0.15 and 6.90 +/- 0.35 ng/mg creatinine (mean +/- SE) in 79 control and 191 DMD samples, respectively. The mean concentration was approximately 2.2-times higher in DMD patients than in controls (p < 0.05). Remarkably, urinary tetranor PGDM concentrations in DMD patients showed chronological changes: it stayed nearly 1.5 times higher than in controls until 7 y but surged at the age of 8 y to a significantly higher concentration.Conclusion: Urinary tetranor PGDM concentrations were shown to be increased in DMD patients and became higher with advancing age. It was indicated that PGD(2)-mediated inflammation plays a role in the pathology of DMD. (C) 2013 Elsevier B.V. All rights reserved.