Novel treatment of neuroinflammation against low back pain by soluble fullerol nanoparticles.
Novel treatment of neuroinflammation against low back pain by soluble fullerol nanoparticles.
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DOI：
10.1097/brs.0b013e31828fc6b7
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发表时间：
2013-08-01
期刊：
影响因子：
3
通讯作者：
Li X
中科院分区：
文献类型：
--
作者：
Liu Q;Jin L;Mahon BH;Chordia MD;Shen FH;Li X
体外研究富勒醇对肿瘤坏死因子-α诱导的小鼠背根神经节的抗炎作用。目的：评价自由基清除剂富勒醇纳米粒在体外对肿瘤坏死因子-α诱导的背根节组织和神经元炎性反应的保护作用。在西方社会，腰痛是临床就诊的最常见原因之一。症状性腰椎间盘(IVD)退变是引起下腰痛的一个重要原因，因为它会导致DRG炎症。活性氧簇(ROS)的产生增加与DRG炎症有关。分离纯化的C3HHeNCr1小鼠背根节组织和神经元，在肿瘤坏死因子-α诱导下进行培养。用H2DCFDA荧光染色测定细胞内ROS含量。用末端脱氧核苷酸转移酶dUTP缺口末端标记法检测细胞凋亡。用实时荧光定量聚合酶链式反应分析神经元炎症和抗氧化酶基因的表达。免疫荧光染色和酶联免疫吸附试验检测DRG组织中炎性细胞因子的表达。荧光染色结果显示，肿瘤坏死因子-α可显著增加细胞内ROS的产生，增加细胞的凋亡率。在富勒醇作用下，细胞凋亡减少，同时ROS受到抑制。富勒醇对炎症细胞因子IL-1β、IL-6、COX-2和PGE_2的表达也有抑制作用，且呈剂量依赖关系。此外，富勒醇处理的细胞表现出抗氧化酶基因SOD2和过氧化氢酶的上调。这项研究的结果清楚地表明，富勒醇治疗通过降低ROS水平和潜在地增强抗氧化酶基因的表达来抑制DRG和神经元的炎症反应，以及细胞凋亡。因此，富勒醇有可能成为一种治疗下腰痛的新型药物。
An in vitro study to investigate the anti-inflammatory effects of fullerol on mouse dorsal root ganglia (DRG) under TNF-α induction. To evaluate the potential of a free radical scavenger, fullerol nanoparticles, to prevent DRG tissue and neuron inflammatory responses under TNF-α induction in vitro. Low back pain is one of the most common reasons for clinician visits in western societies. Symptomatic intervertebral disc (IVD) degeneration is strongly implicated as a cause of low back pain as it results in DRG inflammation. Increased production of reactive oxygen species (ROS) is associated with DRG inflammation. With or without fullerol treatment, DRG tissue and DRG neurons isolated from wild type C3H/HeNCrl mice were cultured under TNF-α induction. The amount of intracellular ROS was measured with H2DCFDA fluorescence staining. Cellular apoptosis was detected via terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The expression of inflammatory as well as anti-oxidative enzyme genes in neurons was analyzed by real-time PCR. In addition, inflammatory cytokine expression in DRG tissue was determined by immunofluorescence staining and enzyme-linked immunosorbent assay (ELISA). Fluorescence staining results indicated that TNF-α markedly increased the production of intracellular ROS and the number of apoptotic cells. Under fullerol treatment cellular apoptosis was reduced along with concomitant suppression of ROS. The expression of inflammatory cytokines IL-1 β, IL-6, COX-2, and PGE2, was also inhibited by fullerol in a dose-dependent manner. Furthermore, fullerol-treated cells exhibited up-regulation of anti-oxidative enzyme genes SOD2 and catalase. The results obtained from this study clearly suggest that fullerol treatment suppresses the inflammatory responses of DRG and neurons, as well as cellular apoptosis by decreasing the level of ROS and potentially enhancing anti-oxidative enzyme gene expression. Therefore, fullerol has potential to serve as a novel therapeutic agent for low back pain treatment.