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首页> 外文期刊>Journal of neuroinflammation >Lipoxins and aspirin-triggered lipoxin alleviate bone cancer pain in association with suppressing expression of spinal proinflammatory cytokines
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Lipoxins and aspirin-triggered lipoxin alleviate bone cancer pain in association with suppressing expression of spinal proinflammatory cytokines

机译：脂蛋白和阿司匹林触发的脂蛋白缓解骨癌疼痛并抑制脊髓促炎细胞因子的表达

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Background The neuroinflammatory responses in the spinal cord following bone cancer development have been shown to play an important role in cancer-induced bone pain (CIBP). Lipoxins (LXs), endogenous lipoxygenase-derived eicosanoids, represent a unique class of lipid mediators that possess a wide spectrum of anti-inflammatory and pro-resolving actions. In this study, we investigated the effects of intrathecal injection with lipoxin and related analogues on CIBP in rats. Methods The CIBP model was induced by intra-tibia inoculation of Walker 256 mammary gland carcinoma cells. Mechanical thresholds were determined by measuring the paw withdrawal threshold to probing with a series of calibrated von Frey filaments. Lipoxins and analogues were administered by intrathecal (i.t.) or intravenous (i.v.) injection. The protein level of LXA4 receptor (ALX) was tested by western blot. The localization of lipoxin receptor in spinal cord was assessed by fluorescent immunohistochemistry. Real-time PCR was carried out for detecting the expression of pro-inflammatory cytokines. Results Our results demonstrated that: 1) i.t. injection with the same dose (0.3?nmol) of lipoxin A4 (LXA4), lipoxin B4 (LXB4) or aspirin-triggered-15-epi-lipoxin A4 (ATL) could alleviate the mechanical allodynia in CIBP on day 7 after surgery. ATL showed a longer effect than the others and the effect lasted for 6?hours. ATL administered through i.v. injection could also attenuate the allodynia in cancer rats. 2) The results from western blot indicate that there is no difference in the expression of ALX among the naive, sham or cancer groups. 3) Immunohistochemistry showed that the lipoxin receptor (ALX)-like immunoreactive substance was distributed in the spinal cord, mainly co-localized with astrocytes, rarely co-localized with neurons, and never co-localized with microglia. 4) Real-time PCR analysis revealed that, compared with vehicle, i.t. injection with ATL could significantly attenuate the expression of the mRNA of proinflammatory cytokines (IL-1β and TNF-α) in the spinal cord in CIBP. Conclusions Taken together, the results of our study suggest that LXs and analogues exert strong analgesic effects on CIBP. These analgesic effects in CIBP are associated with suppressing the expression of spinal proinflammatory cytokines.
机译：背景技术已显示骨癌发展后脊髓中的神经炎症反应在癌症诱发的骨痛（CIBP）中起重要作用。脂氧合蛋白（LXs）是内源性脂氧合酶衍生的类二十烷酸，代表一类独特的脂质介体，具有广泛的抗炎和促分解作用。在这项研究中，我们调查了鞘内注射脂蛋白和相关类似物对大鼠CIBP的影响。方法采用胫骨内接种Walker 256乳腺癌细胞诱导CIBP模型。通过测量爪缩回阈值来确定机械阈值，以使用一系列校准的冯·弗雷丝进行探测。脂质体和类似物通过鞘内（i.t.）或静脉内（i.v.）注射给药。 LXA4受体（ALX）的蛋白质水平通过蛋白质印迹法检测。通过荧光免疫组织化学评估脂质体受体在脊髓中的定位。进行实时PCR以检测促炎细胞因子的表达。结果我们的结果表明：1）i.t.注射相同剂量（0.3nmol）的脂蛋白A4（LXA4），脂蛋白B4（LXB4）或阿司匹林触发的15-表脂蛋白A4（ATL）可以减轻术后7天CIBP的机械异常性疼痛。 ATL的效果比其他ATL更长，效果持续了6个小时。通过i.v.注射还可以减轻癌症大鼠的异常性疼痛。 2）免疫印迹的结果表明，天真的，假的或癌的组之间ALX的表达没有差异。 3）免疫组织化学分析显示，脂蛋白受体（ALX）样免疫反应物质分布在脊髓中，主要与星形胶质细胞共定位，很少与神经元共定位，而从未与小胶质细胞共定位。 4）实时PCR分析显示，与载体相比，注射ATL可以显着减弱CIBP脊髓中促炎细胞因子（IL-1β和TNF-α）mRNA的表达。结论综上所述，我们的研究结果表明LX和类似物对CIBP具有强镇痛作用。 CIBP中的这些镇痛作用与抑制脊髓促炎性细胞因子的表达有关。

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