文献DOI：10.1016/j.neuropharm.2016.12.022

文献PMID：28025096

文献原文链接：http://doi.org.sci-hub.tw/10.1016/j.neuropharm.2016.12.022

Early vs. late intervention of high fat/low dose streptozotocin treated C57Bl/6J mice with enalapril, α-lipoic acid, menhaden oil or their combination: Effect on diabetic neuropathy related endpoints

应用依那普利、α-硫辛酸，鲱鱼油或其组合早期和晚期干预高脂肪/低剂量链脲佐菌素处理的C57Bl / 6J小鼠：对糖尿病神经病变相关终点的影响

【Abstract】

We have previously demonstrated that enalapril, α-lipoic acid and menhaden (fish) oil has potential as a treatment for diabetic peripheral neuropathy. In this study we sought to determine the efficacy of these treatments individually or in combination on multiple neuropathic endpoints in a high fat fed low dose streptozotocin treated mouse, a model of type 2 diabetes, following early or late intervention. Four or twelve weeks after the onset of hyperglycemia, diabetic mice were treated with enalapril, α-lipoic acid, menhaden oil or their combination for 12 weeks. Afterwards, endpoints including glucose tolerance, motor and sensory nerve conduction velocity, thermal nociception, and intraepidermal and cornea nerve fiber density was determined. Glucose clearance was impaired in diabetic mice and significantly improved only with combination treatment and early intervention. Diabetes caused steatosis, slowing of motor and sensory nerve conduction velocity, thermal hypoalgesia and reduction in intraepidermal and cornea nerve fiber density. Treating diabetic mice with enalapril, α-lipoic acid or menhaden oil partially protected diabetic mice from these deficits, whereas the combination of these three treatments was more efficacious following early or late intervention. These studies suggest that a combination therapy may be more effective for treating neural complications of type 2 diabetes.

摘要翻译：

我们之前已经证明，依那普利、α-硫辛酸和鲱鱼（鱼）油具有治疗糖尿病周围神经病变的潜力。在本研究中，我们试图在早期或晚期干预后，在高脂肪喂养的低剂量链脲佐菌素治疗的小鼠（2型糖尿病模型）中单独或组合地确定这些治疗对多个神经病学终点的功效。高血糖发作后4或12周，糖尿病小鼠用依那普利、α-硫辛酸、鲱鱼油或它们的组合治疗12周。然后，确定包括葡萄糖耐量、运动和感觉神经传导速度、热伤害感受以及表皮内和角膜神经纤维密度的终点。糖尿病小鼠的葡萄糖清除率受损，仅在联合治疗和早期干预时显著改善。糖尿病引起脂肪变性、运动和感觉神经传导速度减慢、热痛觉减退和表皮内和角膜神经纤维密度减少。用依那普利、α-硫辛酸或鲱鱼油治疗糖尿病小鼠可部分保护糖尿病小鼠免于这些缺陷，而这三种治疗的组合在早期或晚期干预后均更有效。这些研究表明联合治疗可能更有效地治疗2型糖尿病的神经并发症。