Quantitation of Sudomotor Innervation in Skin Biopsies of Patients With Diabetic Neuropathy
Quantitation of Sudomotor Innervation in Skin Biopsies of Patients With Diabetic Neuropathy
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DOI：
10.1097/nen.0b013e318230b0f4
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发表时间：
2011-10-01
影响因子：
3.2
通讯作者：
Hsieh, Sung-Tsang
中科院分区：
文献类型：
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作者：
Luo, Kai-Ren;Chao, Chi-Chao;Hsieh, Sung-Tsang
以前对神经运动系统的评估依赖于功能测试，只有少数研究在超微结构水平上定量地记录了节后神经变性的病理结果。我们用抗蛋白基因产物9.5(PGP9.5)对神经纤维进行免疫染色，并用刚果红进行反染色，建立了小腿远端皮肤活检组织中神经支配的定量系统。采用计算机化的面积形态计量学分析方法对汗腺神经支配指数(SGII)进行量化，定义为汗腺面积归一化的神经纤维面积。与通常使用的方法相比，这种方法将汗腺面积测量的偏差减小了5.6%(2.47%+/-2.54%比13.97%+/-14.24%，p<；0.001)；因此，SGII的偏差也减少了。我们检查了35名2型糖尿病患者(24名男性和11名女性，平均年龄56.5+/-12.8岁)，他们患有对称性长度依赖性神经病变，表皮内神经纤维密度降低(0.76+/-0.95纤维/毫米)。光镜和电子显微镜下，对照组PGP9.5阳性神经末梢环绕刚果红阳性汗腺分泌线圈；糖尿病患者这些汗腺周围神经末梢不存在或明显减少。糖尿病患者的SGII值低于年龄和性别匹配的对照组(2.60%+/-1.96%比4.84%+/-1.51%，p<；0.0001)。足汗组SGII值低于足汗组(0.89%+/-0.71%vs 3.10%+/-1.94%，p<；0.01)。因此，皮肤活检提供了运动神经支配的联合评估。
Previous assessments of the sudomotor system have depended on functional tests, and only a few studies document the pathologic findings of postganglionic nerve degeneration quantitatively and at the ultrastructural level. We developed a quantitative system of sudomotor innervation in skin biopsies of the distal leg by immunostaining of nerve fibers with anti-protein gene product 9.5 (PGP9.5) and by counterstaining with Congo red. A computerized area-based morphometric analysis was used to quantify the sweat gland innervation index (SGII), defined as the area of nerve fibers normalized to the area of sweat glands. This approach reduced the variations in measurements of sweat gland areas compared to the commonly used method by similar to 5.6-fold (2.47% +/- 2.54% vs 13.97% +/- 14.24%, p < 0.001); hence, variations in SGII were also reduced. We examined 35 Type 2 diabetic patients (24 men and 11 women; mean age, 56.5 +/- 12.8 years), with symmetrical length-dependent neuropathy and reduced intraepidermal nerve fiber density (0.76 +/- 0.95 fibers/mm). By light and electron microscopy, PGP9.5-positive nerve terminals surrounded Congo red-positive sweat gland secretory coils in controls; these periglandular nerve terminals were either absent or markedly reduced in diabetic patients. Diabetic patients had lower SGII values than age-and sex-matched controls (2.60% +/- 1.96% vs 4.84% +/- 1.51%, p < 0.0001). The SGII values were lower in patients with anhidrosis of the feet versus those with normal sweating of the feet (0.89% +/- 0.71% vs 3.10% +/- 1.94%, p < 0.01). Thus, skin biopsy offers combined assessment of sudomotor innervation.