Lipoxins and aspirin-triggered lipoxin alleviate bone cancer pain in association with suppressing expression of spinal proinflammatory cytokines.
Lipoxins and aspirin-triggered lipoxin alleviate bone cancer pain in association with suppressing expression of spinal proinflammatory cytokines.
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脂氧素和阿司匹林触发的脂氧素可减轻骨癌疼痛，并与抑制脊髓促炎细胞因子的表达相关
DOI：
10.1186/1742-2094-9-278
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发表时间：
2012-12-26
影响因子：
9.3
通讯作者：
Wang YQ
中科院分区：
文献类型：
--
作者：
Hu S;Mao-Ying QL;Wang J;Wang ZF;Mi WL;Wang XW;Jiang JW;Huang YL;Wu GC;Wang YQ
研究背景骨癌发生后脊髓内的神经炎性反应在癌因性骨痛(CIBP)中起重要作用。脂氧素(LXs)，内源性脂氧合酶衍生的二十烷基类化合物，代表着一类独特的脂质介质，具有广泛的抗炎和促分解作用。本研究观察鞘内注射脂氧素及其类似物对大鼠CIBP的影响。机械阈值是通过测量爪子回缩阈值来确定的，用一系列校准的冯·弗雷细丝进行探测。鞘内注射脂氧素及其类似物(I.T.)或静脉注射(静注)注射。免疫印迹法检测LXA4受体(ALX)蛋白水平。用荧光免疫组织化学方法检测脊髓内脂氧素受体的定位。实时荧光定量聚合酶链式反应检测促炎细胞因子的表达。术后第7天，注射相同剂量(0.3ATL)的脂氧素A4( )、脂氧素B4(LXB4)或阿司匹林触发的15-表位脂氧素A4(ATL)均可减轻CIBP的机械性痛觉异常。ATL的作用时间最长，可持续6 小时。ATL静脉注射给药。注射用还可减轻癌症大鼠的痛觉过敏。2)免疫印迹结果显示ALX在幼稚组、假手术组和癌变组之间的表达无明显差异。3)免疫组织化学结果显示，脂氧素受体(ALX)样免疫反应物质主要分布在脊髓内，主要与星形胶质细胞共存，很少与神经元共存，与小胶质细胞不共存。4)实时荧光定量聚合酶链式反应分析显示，与Vehicle相比，I.T.结论LXS及其类似物对CIBP有较强的镇痛作用，可显著抑制CIBP大鼠脊髓内致炎细胞因子β和α的表达。CIBP的这些镇痛作用与抑制脊髓促炎细胞因子的表达有关。
BackgroundThe 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.MethodsThe 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.ResultsOur 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.ConclusionsTaken 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.
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影响因子：
2.5
作者：
Gao, Yong-Jing;Ji, Ru-Rong
通讯作者：
Ji, Ru-Rong
影响因子：
7.4
作者：
Medhurst, SJ;Walker, K;Urban, L
通讯作者：
Urban, L
DOI：
10.1016/j.plefa.2005.05.003
发表时间：
2005-09-01
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作者：
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DOI：
10.1097/00041552-199601000-00006
发表时间：
1996-01-01
影响因子：
3.2
作者：
Brady, H R;Serhan, C N
通讯作者：
Serhan, C N