Department of Clinical Neurosciences and the Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
Department of Clinical Neurosciences and the Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
Neurobiol Dis. 2014 Feb;62:18-30. doi: 10.1016/j.nbd.2013.07.019. Epub 2013 Aug 11.
Type 2 diabetes (DM) is the most common cause of peripheral neuropathy in the Western world. A comorbidity, hypertension, has been speculated to contribute to initiation or worsening of diabetic peripheral neuropathy. We studied adult rat models using genetic strains with DM (Zucker Diabetic Fat rats)±hypertension (HTN (ZSF-1 rats)) to investigate the relative contributions of DM and HTN and the potential for additive effects of HTN upon existing DM for the development of peripheral neuropathy. Long duration sensorimotor behavioral and electrophysiological testing was complemented by histological and molecular methods. Only DM led to tactile and thermal hyperalgesia and affected motor nerve electrophysiology. Although DM led to marked loss of sensory amplitudes and to sensory conduction slowing, a mild additive effect from HTN contributed after 6months of DM with worsening of slowing of sensory nerve conduction velocities, but without effect upon sensory amplitudes. At the sensory dominant sural nerve, mild (<10%) but greater degrees of myelin thinning were noted with DM and HTN combined, suggesting a mild additive effect. Matrix metalloproteinase (MMP) expression was increased only at the sural nerve in the presence of HTN with co-localization to Schwann cells and myelin. The effects of DM and HTN upon peripheral nerve are dissimilar, with HTN contributing to MMP upregulation at the sites of myelin thinning at sensory nerve fibers, potentially worsening comorbid DM. Together, our results indicate that HTN has a mild additive contribution to diabetic peripheral neuropathy at sensory peripheral nerve fibers manifesting with the loss of myelin thickness.
2 型糖尿病（DM）是西方世界最常见的周围神经病变的原因。一种合并症，高血压，据推测有助于启动或恶化糖尿病周围神经病变。我们研究了成年大鼠模型，使用具有 DM（Zucker 糖尿病肥胖大鼠）±高血压（HTN（ZSF-1 大鼠））的遗传品系，以研究 DM 和 HTN 的相对贡献，以及 HTN 对现有 DM 发展为周围神经病的潜在附加作用。长期感觉运动行为和电生理测试辅以组织学和分子方法。只有 DM 导致触觉和热痛觉过敏，并影响运动神经电生理学。尽管 DM 导致感觉幅度明显丧失，并导致感觉传导速度减慢，但在 DM 持续 6 个月后，HTN 轻度附加作用导致感觉神经传导速度减慢恶化，但对感觉幅度没有影响。在感觉优势的腓肠神经中，与 DM 和 HTN 联合使用时，观察到轻度（<10%）但更大程度的髓鞘变薄，表明存在轻度附加作用。基质金属蛋白酶（MMP）表达仅在存在 HTN 的情况下在腓肠神经中增加，与施万细胞和髓鞘共定位。DM 和 HTN 对周围神经的影响不同，HTN 导致 MMP 在感觉神经纤维的髓鞘变薄部位上调，可能使合并的 DM 恶化。总之，我们的结果表明，HTN 对感觉周围神经纤维的糖尿病周围神经病变有轻度的附加作用，表现为髓鞘厚度丧失。
