中国组织工程研究

中国组织工程研究 ›› 2016, Vol. 20 ›› Issue (52): 7836-7843.doi: 10.3969/j.issn.2095-4344.2016.52.012

• 材料生物相容性 material biocompatibility • 上一篇    下一篇

亚油酸乙酯抑制钛颗粒诱导的炎症反应及其作用机制

刘国栋1，辛  兵2，黄  栋2，郑  柏1，孙柏寒1，郭开今3 
  

  1. 1徐州医学院研究生学院，江苏省徐州市  221004；徐州医学院附属医院，2脊柱外科，3关节外科，江苏省徐州市  221004
  • 收稿日期:2016-09-25 出版日期:2016-12-16 发布日期:2016-12-16
  • 通讯作者: 郭开今，教授，徐州医学院附属医院关节外科，江苏省徐州市 221004
  • 作者简介:刘国栋，男，1988年生，山东省威海市人，汉族，徐州医科大学在读硕士，主要从事脊柱外科学研究。
  • 基金资助:

    卫生部科研基金(LW201004)；徐州市科技项目基金(XM13B080)

Ethyl linoleate inhibits inflammatory reaction induced by titanium particles and its mechanism

Liu Guo-dong1, Xin Bing2, Huang Dong2, Zheng Bai1, Sun Bai-han1, Guo Kai-jin3
  

  1. 1Graduate School of Xuzhou Medical University, Xuzhou 221004, Jiangsu Province, China; 2Department of Spine Surgery, 3Department of Joint Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221004, Jiangsu Province, China
  • Received:2016-09-25 Online:2016-12-16 Published:2016-12-16
  • Contact: Guo Kai-jin, Professor, Department of Spine Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221004, Jiangsu Province, China
  • About author:Liu Guo-dong, Studying for master’s degree, Graduate School of Xuzhou Medical University, Xuzhou 221004, Jiangsu Province, China
  • Supported by:

    the Science Research Foundation of the Health Department, No. LW201004; the Science and Technology Project of Xuzhou, No. XM13B080

PDF

206

摘要：

文章快速阅读：

 

文题释义：
亚油酸乙酯：是人体必需脂肪酸之一。大量研究表明，亚油酸乙酯具有降低血清胆固醇和低密度脂蛋白的作用，主要用于预防和治疗动脉硬化、心绞痛等疾病，其抗菌、抗炎作用现主要用于化妆品中，用以防止角化过度。曾有研究者研究表明，亚油酸乙酯可减轻细菌脂多糖诱导的炎性因子的释放，但其能否抑制钛颗粒诱导炎性骨溶解及其作用机制尚不清楚。
MAPK级联：是细胞内重要的信号转导系统，它参与胞外信号从表面转导到细胞质及细胞核内的过程，为细胞内信息传递的共同通路。MAPK通路包括ERK、JNK和p38 MAPK等亚族。当细胞受到钛颗粒等外界刺激时，会导致MAPK上游的一系列激酶磷酸化，最终通过双位点磷酸化成为磷酸化P38MAPK，磷酸化ERK MAPK，磷酸化JNK MAPK，激活 MAPK信号转导通路参与炎症反应过程，从而上调炎症细胞因子肿瘤坏死因子α、白细胞介素6等的表达。

背景：有研究证实，亚油酸乙酯可减轻细菌脂多糖诱导的炎性因子释放，但其能否抑制钛颗粒诱导的炎性骨溶解及其作用机制尚不清楚。
目的：观察亚油酸乙酯对钛颗粒诱导炎性因子表达的影响及其作用机制。
方法：将48只昆明小鼠随机分为正常组、钛颗粒组、DMSO组及实验组，正常组不做任何处理；其余3组均建立小鼠钛颗粒背部气囊炎症模型，12 h后，DMSO组向气囊中注入溶媒0.5%二甲基亚砜   200 µL；实验组向气囊中注入5%亚油酸乙酯200 µL。14 d后，苏木精-伊红染色观察各组皮肤组织炎症细胞浸润程度，采用Western blot检测各组抑制性卡巴蛋白、核转录因子κB、诱导型一氧化氮合酶、环氧化酶2、肿瘤坏死因子α、白细胞介素6的表达，以及MAPK通路中ERK、p-erk、JNK、p-JNK、p38与p-p38的表达。
结果与结论：①皮肤组织炎症细胞浸润：钛颗粒组真皮层毛囊陷窝处与皮下疏松结缔组织可见大量炎性细胞浸润及空泡坏死组织；DMSO组与钛颗粒组基本相似；与钛颗粒组比较，实验组真皮层毛囊陷窝处及皮下疏松结缔组织炎性细胞浸润明显减少，空泡坏死组织也有所减少；②Western blot检测结果：与正常组比较，钛颗粒组、DMSO组诱导型一氧化氮合酶、环氧化酶2、核转录因子κB、肿瘤坏死因子α、白细胞介素6、p38、JNK及ERK表达升高(P < 0.05)，抑制性卡巴蛋白降低(P < 0.05)；与钛颗粒组及DMSO组比较，实验组诱导型一氧化氮合酶、环氧化酶2、核转录因子κB、肿瘤坏死因子α、白细胞介素6、p38、JNK及ERK表达降低(P < 0.05)，抑制性卡巴蛋白表达升高(P < 0.05)；③结果表明：亚油酸乙酯可能通过抑制MAPK和核转录因子κB信号通路的激活，显著抑制钛颗粒诱导下炎性因子的表达。

关键词: 生物材料, 材料相容性, 亚油酸乙酯, 钛颗粒, 炎症反应, 核转录因子κB, MAPK

Abstract:

BACKGROUND: Ethyl linoleate has been proved to attenuate the inflammatory-cytokines release induced by lipopolysaccharide, but whether it can inhibit titanium-induced osteolysis and the underlying mechanism remain unclear.
OBJECTIVE: To observe the effect of ethyl linoleate on the expression of inflammatory-related factors induced by titanium particles and explore its mechanism.
METHODS: Forty-eight Kunming mice were randomly divided into blank control, titanium, dimethylsulfoxide (DMSO) and experimental groups. The back air pouch Inflammatory models were established in the mice of the titanium, DMSO and experimental groups, in which the 200 µL menstruum of DMSO (0.5%) and 200 µL ethyl linoleate (0.5%) were respectively administered into the pouch of the mice at 12 hours. Mice in the blank control group received no intervention. Fourteen days later, the inflammatory cell infiltration in the skin was examined through hematoxylin-eosin staining; the expression levels of inhibitor κB-α, nuclear factor-κB, inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-α and interleukin-6 as well as ERK, p-ERK, JNK, p-JNK, p38 and p-p38 in MAPK signaling pathways were evaluated by western blot assay.
RESULTS AND CONCLUSION: In the titanium group and DMSO group, there were numerous inflammatory cells and vacuole-like necrotic tissues in the hair follicle lacuna of dermis and loose connective tissues of hypodermis. The experiment group showed significant reduction in inflammatory cell infiltration and vacuole-like necrosis. Compared with the blank control group, the expression levels of inducible nitric oxide synthase, cyclooxygenase-2, nuclear factor-κB, tumor necrosis factor-α, interleukin-6, ERK, JNK and p38 in the DMSO and titanium groups were significantly increased, while inhibitor κB-α significantly decreased (P < 0.05). Compared with the DMSO and titanium groups, there were significantly down-regulated levels of inducible nitric oxide synthase, cyclooxygenase-2, nuclear factor-κB, tumor necrosis factor-α, interleukin-6, ERK, JNK and p38, and up-regulated inhibitor κB-α level in the experimental group (P < 0.05). In conclusion, ethyl linoleate can remarkably suppress the expressions of titanium-induced inflammatory factors associated with the inhibition of nuclear factor-κB and MAPK signaling pathway activation.

Key words: Titanium, Inflammation, NF-κappa B, Tissue Engineering

中图分类号: