Cytokine-mediated inflammation mediates painful neuropathy from metabolic syndrome.
Cytokine-mediated inflammation mediates painful neuropathy from metabolic syndrome.
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DOI：
10.1371/journal.pone.0192333
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Cheng HT
中科院分区：
文献类型：
--
作者：
Zhang C;Ward J;Dauch JR;Tanzi RE;Cheng HT
疼痛性神经病变（PN）是代谢综合征（MetS）患者的常见疾病。然而，代谢综合征相关痛性神经病（MetSPN）的发病机制尚不清楚。在本研究中，使用高脂肪喂养的小鼠（HF小鼠）研究MetSPN。与对照脂肪喂养（CF）小鼠相比，HF小鼠出现MetS表型，包括体重增加、血浆胆固醇水平升高和胰岛素抵抗。随后，HF小鼠在饮食治疗8周后在后爪中产生机械异常性疼痛和热痛觉过敏。这些疼痛行为与后爪皮肤中伤害性表皮神经纤维和炎性细胞如朗格汉斯细胞和巨噬细胞的密度增加相一致。为了研究MetS对HF小鼠细胞因子表达谱的影响，我们使用多重细胞因子测定来研究背根神经节和血清样品中12种促炎和抗炎细胞因子的蛋白表达。该方法检测了HF小鼠腰背根神经节（LDRG）中促炎细胞因子（包括肿瘤坏死因子（TNF）-α）、白细胞介素（IL）-6、IL-1β）水平的升高以及抗炎细胞因子IL-10水平的降低。IL-10的腹膜内给药降低了HF小鼠中促炎细胞因子的上调并减轻了疼痛行为，而不影响MetS表型。我们的研究结果表明，针对HF诱导的细胞因子失调可能是治疗MetSPN的有效策略。
Painful neuropathy (PN) is a prevalent condition in patients with metabolic syndrome (MetS). However, the pathogenic mechanisms of metabolic syndrome-associated painful neuropathy (MetSPN) remain unclear. In the current study, high-fat-fed mice (HF mice) were used to study MetSPN. HF mice developed MetS phenotypes, including increased body weight, elevated plasma cholesterol levels, and insulin resistance in comparison with control-fat-fed (CF) mice. Subsequently, HF mice developed mechanical allodynia and thermal hyperalgesia in hind paws after 8 wk of diet treatment. These pain behaviors coincided with increased densities of nociceptive epidermal nerve fibers and inflammatory cells such as Langerhans cells and macrophages in hind paw skin. To study the effect of MetS on profiles of cytokine expression in HF mice, we used a multiplex cytokine assay to study the protein expression of 12 pro-inflammatory and anti-inflammatory cytokines in dorsal root ganglion and serum samples. This method detected the elevated levels of proinflammatory cytokines, including tumor necrosis factor (TNF)-α, and interleukin (IL)-6, IL-1β as well as reduced anti-inflammatory IL-10 in lumbar dorsal root ganglia (LDRG) of HF mice. Intraperitoneal administration of IL-10 reduced the upregulation of pro-inflammatory cytokines and alleviated pain behaviors in HF mice without affecting MetS phenotypes. Our findings suggested targeting HF-induced cytokine dysregulation could be an effective strategy for treating MetSPN.
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周围神经病变与胰岛素抵抗相关，与代谢综合征无关
影响因子：
4.8
作者：
Han L;Ji L;Chang J;Wen J;Zhao W;Shi H;Zhou L;Li Y;Hu R;Hu J;Lu B
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Lu B
影响因子：
1.7
作者：
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通讯作者：
Ramirez DC
影响因子：
9.9
作者：
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通讯作者：
Feldman, Eva
DOI：
10.1007/978-1-62703-520-0_11
发表时间：
2013-01-01
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Burguillos, Miguel A
通讯作者：
Burguillos, Miguel A
DOI：
10.1590/s0102-865020160120000010
发表时间：
2016-12-01
期刊：
Acta Cirúrgica Brasileira
影响因子：
--
作者：
Fernandes, Melina Ribeiro;Lima, Nayara Vieira de;Guimarães, Rita de Cássia Avellaneda
通讯作者：
Guimarães, Rita de Cássia Avellaneda