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长春西汀与地塞米松联合使用可减轻鼻咽癌患者放疗损伤后的认知障碍。

Combination of Vinpocetine and Dexamethasone Alleviates Cognitive Impairment in Nasopharyngeal Carcinoma Patients following Radiation Injury.

作者信息

Zhang Ping, Cao Yungang, Chen Songfang, Shao Liang

机构信息

Department of Neurology, Jiangxi Provincial People's Hospital Affiliated to Nanchang University, Nanchang, China.

Department of Geriatrics & Neurology, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, China.

出版信息

Pharmacology. 2021;106(1-2):37-44. doi: 10.1159/000506777. Epub 2020 Apr 15.

Abstract

BACKGROUND

Nasopharyngeal carcinoma (NPC) originates in the nasopharyngeal epithelium. The most common treatments for NPC rT1-4 are radiotherapy and surgery. The pathogenesis of radiation-induced cognitive impairment is complex and includes oxidative stress, mitochondrial dysfunction, neuro-inflammation, and even apoptosis and cell death. Principally, toll-like receptors (TLRs) could regulate the inflammatory/anti-inflammatory balance in patients with radiation-induced brain injury. Vinpocetine has an anti-inflammatory effect as shown in both animal and in vitro studies. Also, dexamethasone is a widely used anti-inflammatory drug. Thus, it is important to test whether addition of vinpocetine could improve the anti-inflammatory properties of dexamethasone for the treatment of NPC patients with radiation-induced brain injuries.

METHODS

A total of 60 NPC patients with radiation-related brain injury were recruited for this study. All subjects were randomly and blindly assigned to the following groups: the dexamethasone group (D group, n = 30) and the vinpocetine and dexamethasone group (VD group, n = 30). Both medicine treatments were uninterrupted for 14 days of administration.

RESULTS

Combined administration of vinpocetine and dexamethasone lowered the expression levels of serum inflammatory cytokines, including TLR2, TLR4, interleukin (IL)-20, IL-8, tumor necrosis factor-α, interferon-γ, monocyte chemoattractant protein 2, and interferon-induced protein 20, when compared to dexamethasone monotherapy. Notably, combination therapy increased antioxidants (superoxide dismutase, glutathione, glutathione peroxidase, and glutathione reductase) and decreased oxidants (thiobarbituric acid reactive substances). Furthermore, combination therapy significantly increased the Mini Mental State Examination score, when compared to dexamethasone monotherapy.

CONCLUSION

Administration of a combination of vinpocetine and dexamethasone may enhance the anti-inflammatory and anti-oxidative effects when compared to dexamethasone monotherapy, which leads to alleviated cognitive impairment in NPC patients with radiation injury.

摘要

背景

鼻咽癌(NPC)起源于鼻咽上皮。鼻咽癌rT1 - 4期最常见的治疗方法是放疗和手术。辐射诱导的认知障碍的发病机制复杂,包括氧化应激、线粒体功能障碍、神经炎症,甚至细胞凋亡和细胞死亡。主要地,Toll样受体(TLRs)可调节辐射性脑损伤患者的炎症/抗炎平衡。长春西汀在动物和体外研究中均显示出抗炎作用。此外,地塞米松是一种广泛使用的抗炎药物。因此,测试添加长春西汀是否能改善地塞米松治疗鼻咽癌放疗后脑损伤患者的抗炎特性具有重要意义。

方法

本研究共招募了60例患有辐射相关脑损伤的鼻咽癌患者。所有受试者被随机且盲法分配到以下组:地塞米松组(D组,n = 30)和长春西汀与地塞米松组(VD组,n = 30)。两种药物治疗均连续给药14天。

结果

与地塞米松单药治疗相比,长春西汀与地塞米松联合给药降低了血清炎症细胞因子的表达水平,包括TLR2、TLR4、白细胞介素(IL)-20、IL-8、肿瘤坏死因子-α、干扰素-γ、单核细胞趋化蛋白2和干扰素诱导蛋白20。值得注意的是,联合治疗增加了抗氧化剂(超氧化物歧化酶、谷胱甘肽、谷胱甘肽过氧化物酶和谷胱甘肽还原酶)并减少了氧化剂(硫代巴比妥酸反应性物质)。此外,与地塞米松单药治疗相比,联合治疗显著提高了简易精神状态检查表评分。

结论

与地塞米松单药治疗相比,长春西汀与地塞米松联合给药可能增强抗炎和抗氧化作用,从而减轻鼻咽癌放疗损伤患者的认知障碍。

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