Blockade of sensory abnormalities and kinin B1 receptor expression by N-Acetyl-L-Cysteine and ramipril in a rat model of insulin resistance
Blockade of sensory abnormalities and kinin B1 receptor expression by N-Acetyl-L-Cysteine and ramipril in a rat model of insulin resistance
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DOI：
10.1016/j.ejphar.2008.05.006
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发表时间：
2008-07-28
影响因子：
5
通讯作者：
Couture, Rejean
中科院分区：
文献类型：
--
作者：
Ismael, Mahmoud Ali;Talbot, Sebastien;Couture, Rejean
葡萄糖喂养的大鼠是一种胰岛素抵抗模型，表现出感觉多发性神经病和高血压。本研究旨在比较 N-乙酰-L-半胱氨酸（NAC，抗氧化剂）和雷米普利（血管紧张素-1 转换酶抑制剂）对长期葡萄糖喂养引起的触觉和冷异常性疼痛的有益作用。还评估了这些治疗对高血压、血浆葡萄糖和胰岛素浓度、胰岛素抵抗和激肽 B 受体表达的影响。雄性 Wistar 大鼠（50-75 克）的饮用水或自来水（对照）中添加 10% D-葡萄糖，持续 11 周。在过去 5 周内，用 NAC（1 g/kg/天，强饲法）、雷米普利（1 mg/kg/天，饮用水中）治疗葡萄糖喂养的大鼠，或者不治疗。 6周的葡萄糖喂养导致收缩压和高血糖显着升高，并伴有触觉和冷痛异常。第11周时，葡萄糖喂养的大鼠的血浆胰岛素、胰岛素抵抗（HOMA指数）、脊髓和肾皮质中的激肽B、受体mRNA以及脊髓中的B、受体结合位点均增强。 NAC 和雷米普利在 6 至 11 周内对触觉和冷异常性疼痛产生渐进性至完全抑制。在葡萄糖喂养的大鼠中，通过这两种治疗方法，高收缩压、高胰岛素血症、胰岛素抵抗和激肽 B 受体的表达也正常化或减弱。结果表明，长期使用抗氧化剂或 ACE 抑制剂治疗对葡萄糖喂养的大鼠的感觉多发性神经病、高血压和胰岛素抵抗具有类似的有益作用。两种疗法均与促伤害性激肽 B 受体表达减少相关。 (C) 2008 Elsevier B.V. 保留所有权利。
Glucose-fed rat is a model of insulin resistance that displays sensory polyneuropathy and hypertension. This study aimed at comparing the beneficial effects of N-Acetyl-L-Cysteine (NAC, antioxidant) and ramipril (angiotensin-1 converting enzyme inhibitor) on tactile and cold allodynia induced by chronic glucose feeding. Impact of these treatments was also assessed on hypertension, plasma glucose and insulin concentrations, insulin resistance and kinin B, receptor expression. Male Wistar rats (50-75 g) were given 10% D-glucose in their drinking water for 11 weeks or tap water (controls). Glucose-fed rats were treated either with NAC (1 g/kg/day, gavage), ramipril (1 mg/kg/day in drinking water) or no drug during the last 5 weeks. Glucose feeding for 6 weeks induced a significant increase in systolic blood pressure and hyperglycaemia which was accompanied by tactile and cold allodynia. At 11 weeks, plasma insulin, insulin resistance (HOMA index), kinin B, receptor mRNA in spinal cord and renal cortex and B, receptor binding sites in spinal cord were enhanced in glucose-fed rats. NAC and ramipril caused a progressive to complete inhibition of tactile and cold allodynia from 6 to 11 weeks. High systolic blood pressure, hyperinsulinemia, insulin resistance and kinin B, receptor expression were also normalized or attenuated in glucose-fed rats by either treatment. Results suggest that chronic treatment with an antioxidant or an ACE inhibitor provides similar beneficial effects on sensory polyneuropathy, hypertension and insulin resistance in glucose-fed rats. Both therapies were associated with a reduction of the expression of the pro-nociceptive kinin B, receptor. (C) 2008 Elsevier B.V. All rights reserved.