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日本研究人员关于肯尼迪病人某些生理参数和正常人对比的研究论文


病友黑-阿米其检索到一篇日本研究人员发表的新的论文。转载如下:
 

Abstract

 This study aimed to evaluate various metabolic parameters in patients with spinal and bulbar muscular atrophy (SBMA), to investigate the association between those indices and disease severity, and to explore the underlying molecular pathogenesis.
 We compared the degree of obesity, metabolic parameters, and blood pressure in 55 genetically confirmed SBMA patients against those in 483 age- and sex-matched healthy control. In SBMA patients, we investigated the correlation between these factors and motor functional indices. SBMA patients had lower body mass index, blood glucose, and Hemoglobin A1c, but higher blood pressure, homeostasis model assessment of insulin resistance (HOMA-IR, a marker of insulin resistance), total cholesterol, and adiponectin levels than the control subjects.
 There were no differences in visceral fat areas, high-density lipoprotein-cholesterol (HDL-C), or triglyceride levels in two groups. Revised amyotrophic lateral sclerosis functional rating scale (ALSFRS-R) correlated positively with HDL-C, but negatively with HOMA-IR. Through stepwise multiple regression analysis, we identified HOMA-IR as a significant metabolic determinant of ALSFRS-R.
 In biochemical analysis, we found that decreased expressions of insulin receptor,insulin receptor substrate-1 and insulin receptor-β, in autopsied muscles and fibroblasts of SBMA patients. This study demonstrates that SBMA patients have insulin resistance, which is associated with the disease severity. The expressions of insulin receptors are attenuated in the skeletal muscle of SBMA, providing a possible pathomechanism of metabolic alterations. These findings suggested that insulin resistance is a metabolic index reflecting disease severity and pathogenesis as well as a potential therapeutic target for SBMA.

(译文)

    本研究的目的是求得肯尼迪病人的不同代谢参数,以调查这些指数和疾病严重程度之间的关系,并探索潜在的分子水平的发病机制。我们对55名经基因测量确诊的肯尼迪病人和483名年龄,性别相匹配的健康者进行了肥胖,代谢参数和血压程度的对比。在肯尼迪病人中,我们调查了这些参数和运动功能的相关性。肯尼迪病患者和健康者对比,有着较低的体重参数,血液葡萄糖浓度和糖化血红蛋白浓度,但是有着较高的血压,胰岛素抵抗的稳态模式评估值(一种胰岛素抵抗的标记),总胆固醇和脂联素水平。在内脏脂肪面积,高密度脂蛋白胆固醇,或者甘油三酯水平,两组观测者没有不同。修正的肌萎缩侧索硬化功能评定量比率和高密度脂蛋白-胆固醇呈正相关,但是和胰岛素抵抗呈负相关。通过逐步多元回归分析,我们确定胰岛素抵抗是衡量肌萎缩侧索硬化功能评定量比率的重要的代谢因素。  
   利用生物化学分析,我们发现在肯尼迪病人解剖的肌肉和纤维细胞中,胰岛素受体,胰岛素受体基底-1和胰岛素受体-β有降低的表现。这一研究表明肯尼迪病人有着胰岛素抵抗,而这种抵抗是和疾病的严重程度相关联的。在肯尼迪病人的骨骼肌中,胰岛素受体的表现是衰减的。这提供了一个可能的代谢改变的病理机制。这一发现意味着胰岛素抵抗是一个代谢指标,它反映了疾病的严重程度和发病机制,同时可能是潜在的治疗肯尼迪病的靶目标。



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