糖尿病周围神经病的病理学研究

Pathological characteristics of diabetic peripheral neuropathy

目的用形态计量的方法明确不同程度糖尿病周围神经病(DPN)病变的病理学特点,并分析其神经损伤程度与临床情况的相关性。方法 1收集14例DPN患者及5例与糖尿病无关的尸检病例,进行腓肠神经活检;2光镜、电镜观察和判断神经病变;3应用免疫组化En Vision二步法检测NF、MBP、PMP22和S-100蛋白的表达情况,进一步观察神经病变情况,特别是Schwann细胞的功能状态;4从轴索、髓鞘、Schwann细胞、血管、神经束膜5个方面,应用Image-Pro Plus图像分析系统进行测定和分析。结果 DPN病变特点:1有髓纤维密度显著降低,而小直径纤维数量增加并对应较大的g-ratio值(尤其是轻度病变)时,说明髓鞘脱失与再生并存;2轴索病变显著,髓鞘改变较轻,提示轴索变性可能是造成有髓纤维减少的主要原因;3Schwann细胞数目显著增加(P<0.05),但并不形成新的髓鞘,且MBP和PMP22表达下调,提示新生Schwann细胞功能异常;4微血管病变主要为管壁基底膜样物质沉积,管壁结构不清,管腔狭窄;5神经束膜增厚是DPN特征性病变,主要是束膜细胞外基质增加所致。结论本实验显示,DPN的病理特点为有髓纤维数目明显减少,轴索变性,脱髓鞘,Schwann细胞增生,血管壁基底膜样物质沉积,神经束膜增厚。DPN病变程度常与临床表现不一致,因此腓肠神经活检对诊断和研究DPN非常重要。

Objective To define the pathological characteristics of diabetic peripheral neuropathy（ DPN） in varying degrees,and to analyse the associations between the nervous damages and clinical conditions. Methods Fourteen sural nerve samples of DPN and 5 control subjects（ from autopsy） were collected; The optical and electron microscopy was used to evaluate the peripheral neuropathy; Immunohistochemistry was carried out to detect the expression of NF,MBP,PMP22 and S-100 in the neuropathy; The software of Image-Pro Plus was used to measure and analyse the alterations of axon,myelin sheath,schwann cells,vessels and perineurium. Results The pathological features of DPN were as follows： 1. Diabetic patients demonstrated a significant reduction（ P 0. 01） in myelinated fibre density. However,an increase in the proportion of small myelinated fibers with relatively larger value of g ratio demonstrated demyelination and remyelination or the presence of regenerative fibres in this population,especially mild neuropathy,compared to control subjects; 2. Axonal degeneration was more serious than that of myelin lesions,suggesting axonal degeneration might be the main cause of myelinated fiber decrease;3. An increase in the percentage of unassociated Schwann cell profiles（ P 0. 01） and the down-regulated expression of MBP and PMP22 suggested the abnormality of the proliferated Schwann cells. 4. Microvasculopathy was mainly manifested by the deposition of basement membrane-like materials in microvessel walls and stenosis or occlusion of microvessel lumens; 5.Perineurial thickening was the characteristic lesion of DPN,in which the major cause was the increase of perineurial extracellular matrix. Conclusions The results in this study show that the pathological features of DPN are the decrease of mylinated fiber quantity,axonal degeneration,demyelination,Schwann cell proliferation,the sedimentation of PAS positive materials in the wall of arterioles,and perineurial thickening. The clinical manifestations fail to correlate with the severity of DPN,and so the sural nerve biopsy is important to the diagnosis and study of DPN.