Veteran Affairs Medical Center, University of Iowa, Iowa City, IA 52246, USA.
Diabetes Metab Res Rev. 2010 May;26(4):306-18. doi: 10.1002/dmrr.1088.
The objective of this study was to determine the effect of diet-induced obesity (DIO) on microvascular and neural function.
Rats were fed a standard or high fat diet for up to 32 weeks. The following measurements were carried out: vasodilation in epineurial arterioles using videomicroscopy, endoneurial blood flow using hydrogen clearance, nerve conduction velocity using electrical stimulation, size-frequency distribution of myelinated fibres of the sciatic nerve, intraepidermal nerve fibre density using confocal microscopy and thermal nociception using the Hargreaves method.
Rats fed a high fat diet for 32 weeks developed sensory neuropathy, as indicated by slowing of sensory nerve conduction velocity and thermal hypoalgesia. Motor nerve conduction velocity and endoneurial blood flow were not impaired. Mean axonal diameter of myelinated fibres of the sciatic nerve was unchanged in high fat-fed rats compared with that in control. Intraepidermal nerve fibre density was significantly reduced in high fat-fed rats. Vascular relaxation to acetylcholine and calcitonin gene-related peptide was decreased and expression of neutral endopeptidase (NEP) increased in epineurial arterioles of rats fed a high fat diet. In contrast, insulin-mediated vascular relaxation was increased in epineurial arterioles. NEP activity was significantly increased in the skin of the hindpaw. Markers of oxidative stress were increased in the aorta and serum of high fat-fed rats but not in epineurial arterioles.
Chronic obesity causes microvascular and neural dysfunction. This is associated with increased expression of NEP but not oxidative stress in epineurial arterioles. NEP degrades vasoactive peptides, which may explain the decrease in microvascular function.
本研究旨在确定饮食诱导肥胖（DIO）对微血管和神经功能的影响。
大鼠给予标准或高脂肪饮食，最长达 32 周。进行以下测量：使用视频显微镜测量神经外膜动脉的血管舒张，使用氢清除法测量神经内膜血流，使用电刺激测量神经传导速度，使用坐骨神经有髓纤维大小-频率分布测量仪测量有髓纤维的大小-频率分布，使用共聚焦显微镜测量表皮内神经纤维密度，使用 Hargreaves 法测量热痛觉过敏。
给予高脂肪饮食 32 周的大鼠出现感觉神经病变，表现为感觉神经传导速度减慢和热痛觉过敏。运动神经传导速度和神经内膜血流不受影响。与对照组相比，高脂肪饮食组大鼠的坐骨神经有髓纤维平均轴突直径无变化。高脂肪饮食组大鼠表皮内神经纤维密度显著降低。乙酰胆碱和降钙素基因相关肽诱导的血管舒张减弱，神经外膜动脉中性内肽酶（NEP）表达增加。相比之下，胰岛素介导的血管舒张增加。NEP 活性在大鼠后足皮肤中显著增加。高脂肪饮食大鼠的主动脉和血清中氧化应激标志物增加，但神经外膜动脉中没有增加。
慢性肥胖导致微血管和神经功能障碍。这与神经外膜动脉中 NEP 的表达增加而氧化应激没有增加有关。NEP 降解血管活性肽，这可能解释了微血管功能的下降。
