利波西汀对糖尿病神经病变大鼠脊髓背角BDNF、Synaptophysin和PSD-95水平的影响

IF 0.3 Q4 MEDICINE, RESEARCH & EXPERIMENTAL
Nazlı Turan Yücel, Umut İrfan Üçel, Ümide Demir Özkay, E. Ulupınar, Ö. Can
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引用次数: 0

摘要

目的:众所周知,神经性疼痛伴随着脊髓背角微环境中神经营养因子和突触蛋白水平的改变。这些变化导致痛觉过敏和异常性疼痛过程;因此,镇痛药物可以通过影响这些内源性物质的表达、水平或功能来发挥药理作用。在本研究中,基于利波西汀(一种选择性去甲肾上腺素再摄取抑制剂)在糖尿病神经病变中具有抗痛觉作用的认识,我们旨在研究这种药物对糖尿病诱导的脑源性神经营养因子(BDNF)、突触素(突触整合的突触前标记物)、和背角浅层突触后密度-95 (PSD-95)(突触后整合的标记物)水平。方法:大鼠单剂量注射链脲佐菌素(STZ) (50 mg/kg)诱导实验性糖尿病。在4周的疼痛性糖尿病神经病变诱导期后,大鼠口服8 mg/kg利波西汀2周。采用Randall-Selitto和Hargreave试验评估痛觉过敏反应。在疼痛测试之后,进行免疫组织化学研究。结果:利波西汀给药2周后,糖尿病大鼠神经性疼痛试验中足部戒断阈值降低,足部戒断潜伏期缩短,表明该药具有抗痛觉作用。此外,利波西汀可逆转糖尿病大鼠BDNF和突触素水平的增强。然而,在stz -糖尿病大鼠和利博西汀治疗的stz -糖尿病大鼠中,PSD-95的密度没有改变。结论:利波西汀对糖尿病大鼠的抗痛觉作用可能与抑制中枢致敏和调节脊柱可塑性有关。然而,还需要进一步的研究来阐明确切的作用机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Effect of Reboxetine Treatment on BDNF, Synaptophysin, and PSD-95 Levels in the Spinal Dorsal Horn of Rats with Diabetic Neuropathy
Objective: It is known that neuropathic pain is accompanied by alterations in the levels of neurotrophic factors and synaptic proteins in the microenvironment of the spinal dorsal horn. Such changes contribute to hyperalgesia and allodynia processes; thus, analgesic drugs can exert their pharmacological effects by affecting the expressions, levels, or functions of these endogenous substances. In this study, based on the knowledge that reboxetine (a selective noradrenaline reuptake inhibitor) has the potential for antihyperalgesic efficacy in diabetic neuropathy, we aimed to examine the probable effects of this drug on diabetes-induced changes in brain-derived neurotrophic factor (BDNF), synaptophysin (the pre-synaptic marker of synaptic integration), and postsynaptic density-95 (PSD-95) (the postsynaptic marker of synaptic integration) levels in the superficial laminae of the dorsal horn. Methods: Experimental diabetes was induced by a single-dose injection of streptozotocin (STZ) (50 mg/kg) in rats. After four week-long induction period of painful diabetic neuropathy, rats were treated orally with 8 mg/kg reboxetine for two weeks. Hyperalgesia responses were evaluated by using the Randall–Selitto and Hargreave's tests. Following the pain tests, immunohistochemical studies were performed. Results: Two weeks of reboxetine administration increased the reduced paw withdrawal thresholds and shortened the paw withdrawal latencies of diabetic rats in neuropathic pain tests, indicating the antihyperalgesic efficacy of this drug. Moreover, augmented BDNF and synaptophysin levels in diabetic rats reversed by reboxetine treatment. However, there was no alteration in the densities of PSD-95, in both STZ-diabetic and reboxetine-treated STZ-diabetic rats. Conclusion: The obtained results suggested that inhibition of central sensitization and modulation of spinal plasticity seem to be pharmacological mechanisms underlying reboxetine's antihyperalgesic effects on diabetic rats. However, further studies are still needed to clarify the exact mechanism of action.
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来源期刊
Clinical and Experimental Health Sciences
Clinical and Experimental Health Sciences MEDICINE, RESEARCH & EXPERIMENTAL-
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