Yao Lu, Wu Yun-Tao, Tian Guo-Xiang, Xia Chang-Quan, Zhang Feng, Zhang Wei
Department of Forth Cadre, PLA Army General Hospital, No. 5 Nanmencang, Dongcheng District, Beijing, 10070, China.
Anat Rec (Hoboken). 2017 Oct;300(10):1858-1864. doi: 10.1002/ar.23618. Epub 2017 Jul 25.
Diabetes-induced neuropathic pain (DNP) substantially influences people's life qualities. Hyperglycemia-induced excess free radicals have been considered as the most critical mechanisms underlying DNP. As an unsaturated aldehyde and a reactive product of lipid peroxidation, acrolein plays critical roles in diabetic nephropathy and inflammatory pain. We sought to determine whether acrolein is involved in DNP in this study. Diabetes was induced by a single intraperitoneal (i.p.) injection of 60 mg/kg streptozotocin (STZ). An acrolein scavenger hydralazine (5 mg/kg) was administered through a daily injection for 4 weeks, starting immediately within 30 min after STZ injection. Western blot showed that hydralazine could effectively inhibit STZ-induced upregulation of acrolein in the spinal dorsal horn on day 7-28 after STZ injection. Behavioral tests showed that STZ injection induced significant mechanical allodynia and thermal hyperalgesia, which could be alleviated by hydralazine. Immunofluorescent histochemistry and Western blot showed that STZ induced significant microglial activation. ELISA data indicated upregulation of inflammatory cytokines IL-1β and TNF-α expression in the spinal dorsal horn. Furthermore, hydralazine effectively attenuated microglial activation and expression of inflammatory mediators. Our data indicate that acrolein might be involved in the development of neuroinflammation and behavioral consequences of DNP. Anat Rec, 2017. © 2017 Wiley Periodicals, Inc. Anat Rec, 300:1858-1864, 2017. © 2017 Wiley Periodicals, Inc.
糖尿病性神经病理性疼痛（DNP）严重影响人们的生活质量。高血糖诱导产生的过量自由基被认为是DNP最关键的潜在机制。丙烯醛作为一种不饱和醛以及脂质过氧化的反应产物，在糖尿病肾病和炎性疼痛中发挥着关键作用。在本研究中，我们试图确定丙烯醛是否参与DNP的发生。通过单次腹腔注射60 mg/kg链脲佐菌素（STZ）诱导糖尿病。从STZ注射后30分钟内立即开始，每天注射一次丙烯醛清除剂肼屈嗪（5 mg/kg），持续4周。蛋白质免疫印迹法显示，在STZ注射后第7 - 28天，肼屈嗪可有效抑制STZ诱导的脊髓背角中丙烯醛的上调。行为测试表明，注射STZ会引起明显的机械性异常性疼痛和热痛觉过敏，而肼屈嗪可以缓解这些症状。免疫荧光组织化学和蛋白质免疫印迹法显示，STZ可诱导小胶质细胞显著活化。酶联免疫吸附测定（ELISA）数据表明脊髓背角中炎性细胞因子白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）表达上调。此外，肼屈嗪可有效减轻小胶质细胞活化以及炎性介质的表达。我们的数据表明，丙烯醛可能参与了DNP的神经炎症发展及行为后果。《解剖学记录》，2017年。© 2017威利期刊公司。《解剖学记录》，300:1858 - 1864，2017年。© 2017威利期刊公司。
