Expression of neurotrophic factors in diabetic muscle-relation to neuropathy and muscle strength
Expression of neurotrophic factors in diabetic muscle-relation to neuropathy and muscle strength
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DOI：
10.1093/brain/awp208
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发表时间：
2009-10-01
期刊：
影响因子：
14.5
通讯作者：
Andersen, H.
中科院分区：
文献类型：
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作者：
Andreassen, C. S.;Jakobsen, J.;Andersen, H.
糖尿病多发性神经病变可导致远端横纹肌萎缩和无力，由于去神经支配。缺乏神经营养支持被认为有助于糖尿病神经病变的发展。在这项研究中，我们测量了42名糖尿病患者和20名健康对照者的腓肠肌和三角肌肌肉活检组织中神经生长因子（NGF）、脑源性神经营养因子（BDNF）、神经营养因子3 （NT-3）、神经营养因子4 （NT-4）和睫状体神经营养因子（CNTF）的表达。为了表达远端神经病变梯度并减少个体间差异，计算了腓肠肌和三角肌中所有神经营养因子的远端/近端表达水平之比。通过临床检查、电生理研究和定量感觉检查确定糖尿病患者的神经病变状态，并通过等速动力学法评估肩关节和踝关节的肌肉力量。糖尿病患者NT-3远端/近端比值[中位数（范围）110.7(39.8-546.8)]低于对照组[157.6 (63.3-385.4)]；（P < 0.05）]，神经性糖尿病患者[107.1(39.8-326.0)]与无神经性糖尿病患者[134.5 (46.6-546.8)]；（p < 0.005）]。此外，NT-3的比值与肌力相关（r(s) = 0.41, P < 0.01），并与所有神经病变指标的综合评分呈负相关趋势[神经病变秩和评分（NRSS）] （r(s) = -0.27, P = 0.09）。NT-4的比率也观察到类似的趋势。NGF （r(s) = -0.32, P < 0.05）和BDNF （r(s) = -0.32, P < 0.05）与NRSS相关，但与肌力无关。糖尿病患者的CNTF比率[64.6(23.7-258.7)]高于对照组[50.2 (27.2-186.4)]；（P < 0.05）]，但与NRSS和肌力均无相关性。我们的研究结果表明，NT-3在糖尿病患者横纹肌中的表达降低，与肌肉无力和神经病变有关。我们认为NT-3的缺乏导致糖尿病神经病变中肌肉力量的丧失。
Diabetic polyneuropathy can lead to atrophy and weakness of distally located striated muscles due to denervation. Lack of neurotrophic support is believed to contribute to the development of diabetic neuropathy. In this study, we measured the expression of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), neurotrophin 4 (NT-4) and ciliary neurotrophic factor (CNTF) in muscle biopsies taken from the gastrocnemic and deltoid muscles in 42 diabetic patients and 20 healthy control subjects. To express the distal neuropathic gradient and to reduce interindividual variation, a distal/proximal ratio between expression levels in the gastrocnemic and deltoid muscles was calculated for all neurotrophic factors. Neuropathic status was determined by clinical examination, electrophysiological studies and quantitative sensory examination in diabetic patients, and muscle strength at both the shoulder and ankle was assessed by isokinetic dynamometry. Distal/proximal ratios for NT-3 were lower in diabetic patients [median (range) 110.7 (39.8-546.8)] than in controls [157.6 (63.3-385.4); (P < 0.05)], and in neuropathic diabetic patients [107.1 (39.8-326.0)] versus patients without neuropathy [134.5 (46.6-546.8); (P < 0.005)]. Further, ratios for NT-3 were related to muscle strength (r(s) = 0.41, P < 0.01) and showed a tendency towards a negative relationship to the combined score of all measures of neuropathy [Neuropathy rank-sum score (NRSS)] (r(s) = -0.27, P = 0.09). Similar trends were observed for ratios for NT-4. Ratios for NGF (r(s) = -0.32, P < 0.05) and BDNF (r(s) = -0.32, P < 0.05) were related to NRSS, but not to muscle strength. Ratios for CNTF were higher in diabetic patients [64.6 (23.7-258.7)] compared with controls [50.2 (27.2-186.4); (P < 0.05)], but showed no relationship to neither NRSS nor muscle strength. Our results show that the expression of NT-3 is reduced in striated muscles in diabetic patients and is related to muscle weakness and neuropathy. We suggest that lack of NT-3 contributes to insufficient re-innervation leading to the loss of muscle strength in diabetic neuropathy.