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神经生长因子及其受体在糖尿病周围神经病变患者中的表达。

Nerve growth factor and expression of its receptors in patients with diabetic neuropathy.

机构信息

Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Korea.

出版信息

Diabet Med. 2009 Dec;26(12):1228-34. doi: 10.1111/j.1464-5491.2009.02856.x.

DOI:10.1111/j.1464-5491.2009.02856.x
PMID:20002474
Abstract

AIMS

Low serum nerve growth factor (NGF) levels have been reported in patients with diabetic peripheral neuropathy (DPN), but the role of NGF in the development of neuropathy is unclear. Thus, we investigated the associations of serum NGF level and NGF receptor activity with the presence and severity of DPN.

METHODS

One hundred and thirty-six patients with Type 2 diabetes were included in this cross-sectional study. Serum NGF levels were measured by ELISA. Expressions of NGF receptors (TrkA and p75(NTR)) were measured by immunohistochemical staining. The presence and severity of DPN were assessed by neuropathy disability score (NDS) and by corneal nerve fibre length (cNFL) and nerve branch density (cNBD) using in vivo confocal microscopy.

RESULTS

Patients with DPN had higher serum NGF levels (56-451 pg/ml) than patients without DPN (4-54 pg/ml). However, in DPN patients, serum NGF was negatively associated with neuropathy severity (mild 222 +/- 64 pg/ml; moderate 114 +/- 17 pg/ml; severe 89 +/- 20 pg/ml). This negative association was consistent in all severity indices (NDS, P < 0.001; cNFL, P < 0.001; cNBD P = 0.010) even after adjustment for age, sex, diabetes duration, insulin use, fasting glucose and glycated haemoglobin. Although NGF receptor activities had significantly (P < 0.05) negative associations with the presence and severity of neuropathy, these associations were not significant when adjusted for other factors.

CONCLUSIONS

Serum NGF level was positively associated with the presence of DPN but negatively associated with neuropathy severity in DPN patients. The change in serum NGF might be a consequence of, rather than a contributor to, the early development of DPN.

摘要

目的

已有研究报道,糖尿病周围神经病变(DPN)患者的血清神经生长因子(NGF)水平较低,但 NGF 在神经病变发展中的作用尚不清楚。因此,我们研究了血清 NGF 水平和 NGF 受体活性与 DPN 的发生和严重程度的相关性。

方法

本横断面研究纳入了 136 例 2 型糖尿病患者。采用 ELISA 法检测血清 NGF 水平,免疫组化染色法检测 NGF 受体(TrkA 和 p75(NTR))的表达。采用神经病变残疾评分(NDS)和活体共聚焦显微镜检测角膜神经纤维长度(cNFL)和神经分支密度(cNBD)评估 DPN 的发生和严重程度。

结果

有 DPN 的患者血清 NGF 水平(56-451 pg/ml)高于无 DPN 的患者(4-54 pg/ml)。然而,在 DPN 患者中,血清 NGF 与神经病变严重程度呈负相关(轻度患者 222 +/- 64 pg/ml;中度患者 114 +/- 17 pg/ml;重度患者 89 +/- 20 pg/ml)。这种负相关在所有严重程度指标中均一致(NDS,P < 0.001;cNFL,P < 0.001;cNBD,P = 0.010),即使在调整了年龄、性别、糖尿病病程、胰岛素使用、空腹血糖和糖化血红蛋白后也是如此。尽管 NGF 受体活性与神经病变的发生和严重程度呈显著负相关(P < 0.05),但在调整其他因素后,这种相关性并不显著。

结论

血清 NGF 水平与 DPN 的发生呈正相关,与 DPN 患者的神经病变严重程度呈负相关。血清 NGF 的变化可能是 DPN 早期发生的结果,而不是其促成因素。

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