The monoacylglycerol lipase inhibitor JZL184 decreases inflammatory response in skeletal muscle contusion in rats
The monoacylglycerol lipase inhibitor JZL184 decreases inflammatory response in skeletal muscle contusion in rats
复制标题
单酰基甘油脂肪酶抑制剂 JZL184 可降低大鼠骨骼肌挫伤的炎症反应。
DOI：
10.1016/j.ejphar.2015.04.018
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发表时间：
2015-08-15
影响因子：
5
通讯作者：
Guan, Da-Wei
中科院分区：
文献类型：
--
作者：
Jiang, Shu-Kun;Zhang, Miao;Guan, Da-Wei
肌肉创伤愈合过程是一个典型的炎症诱发事件。单酰基甘油脂肪酶（MAGL）抑制剂（4-硝基苯基）4-[双（1，3-苯并二氧杂环戊烯-5-基）-羟甲基]哌啶-1-羧酸酯（JZL 184）先前已被报道可减轻小鼠结肠炎和急性脊髓损伤的炎症，这为骨骼肌损伤的初级护理提供了新的策略。我们研究了JZL 184对大鼠肌肉挫伤模型炎症的影响，发现中性粒细胞和巨噬细胞浸润以及促炎细胞因子表达减少。随着创伤后时间的延长，I型胶原和mRNA表达异常的成纤维细胞浸润明显阻碍了肌纤维的再生，并促进了纤维化。此外，1-（2，4-二氯苯基）-5-（4-碘苯基）-4-甲基-N-吗啉-4-基吡唑-3-甲酰胺（AM 281，一种选择性大麻素CB 1受体拮抗剂）和[6-碘-2-甲基-1-（2-吗啉-4-乙基）吲哚-3-基]-（4-甲氧基苯基）甲酮（AM 630，一种选择性大麻素CB 2受体拮抗剂）处理减轻了JZL 184的抗炎作用。我们的研究结果表明，JZL 184能够抑制炎症反应并干扰挫伤肌肉愈合，其中抗炎作用可能是通过大麻素CB 1和CB 2受体介导的。(C)2015 Elsevier BM.版权所有© 2016
Muscle wound healing process is a typical inflammation-evoked event. The monoacylglycerol lipase (MAGL) inhibitor (4-nitrophenyl)4-[bis(1,3-benzodioxol -5-yl)-hydroxymethyl]pipericline-1-carboxylate (JZL184) has been previously reported to reduce inflammation in colitis and acute king injury in mice, which provide a new strategy for primary care of skeletal muscle injury. We investigated the effect of JZL184 on inflammation in rat muscle contusion model, and found decreased neutrophil and macrophage infiltration and pro inflammatory cytokine expression. With extension of post traumatic interval, myofiber regeneration was significantly hindered with increased collagen types I and ill mRNAfibmblast infiltration as well as promoted fibrosis. Furthermore, 1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-morpholin-4-ylpyrazole-3-carboxamide (AM281, a selective cannabinoid CBI receptor antagonist) and [6-iodo-2-methyl-1-(2-morpholin-4-ylethyl)indol-3-yl]-(4-methoxyphenyl)methanone (AM630, a selective cannabinoid CB2 receptor antagonist) treatment alleviated the anti-inflammatory effect of JZL184. Our findings demonstrate that JZL184 is able to inhibit the inflammatory response and interfere with contused muscle healing, in which the anti-inflammatory action may be mediated through cannabinoicl CB1 and CB2 receptors. (C) 2015 Elsevier BM. All rights reserved,