Zhang Miao, Jiang Shu-Kun, Tian Zhi-Ling, Wang Meng, Zhao Rui, Wang Lin-Lin, Li Shan-Shan, Liu Min, Li Jiao-Yong, Zhang Meng-Zhou, Guan Da-Wei
Department of Forensic Pathology, China Medical University School of Forensic Medicine Shenyang 110122, Liaoning Province, P. R. China.
Department of Forensic Pathology, China Medical University School of Forensic Medicine Shenyang 110122, Liaoning Province, P. R. China ; Remote Forensic Consultation Center, Collaborative Innovation Center of Judicial Civilization, China University of Political Science and Law Beijing 100192, P. R. China.
Int J Clin Exp Pathol. 2015 Apr 1;8(4):3491-502. eCollection 2015.
Skeletal muscle injuries repair typically is an overlapping event between inflammation and tissue repair. Our previous study has demonstrated that activation of cannabinoid receptor type 2 (CB2R) by JWH-133 alleviates fibrosis in the repair of rat skeletal muscle contusion. Meanwhile, accumulated data show that CB2R stimulation exerts anti-inflammatory property in sepsis and cystitis. However, the effects of CB2R on inflammatory cytokines in response to the repair of skeletal muscle contusion are still unknown. In this study, we used selective agonist or antagonist of CB2R to observe the role of CB2R on inflammation and fibrogenesis during the repair of contused skeletal muscles in rats. Our results revealed that treatment with Gp1a, a selective CB2R agonist, significantly decreased the infiltration of neutrophils and macrophages, the expression of pro-inflammatory cytokines MCP-1, TNF-α, IL-1β and IL-6, the expression of pro-fibrotic cytokines IL-4, IL-13, TGF-β and P-Smad3 while increased anti-fibrotic cytokine IL-10 production as compared with Vehicle. The opposite results were observed in the CB2R inhibition group with AM630. Our study demonstrated that CB2R orchestrates fibrogenesis through regulation of inflammatory response during the repair of skeletal muscle contusion.
骨骼肌损伤修复通常是炎症与组织修复重叠的过程。我们之前的研究表明，JWH-133激活大麻素2型受体（CB2R）可减轻大鼠骨骼肌挫伤修复过程中的纤维化。同时，大量数据表明，刺激CB2R在脓毒症和膀胱炎中具有抗炎特性。然而，CB2R对骨骼肌挫伤修复过程中炎性细胞因子的影响仍不清楚。在本研究中，我们使用CB2R的选择性激动剂或拮抗剂来观察CB2R在大鼠挫伤骨骼肌修复过程中对炎症和纤维化形成的作用。我们的结果显示，与溶剂对照组相比，选择性CB2R激动剂Gp1a治疗显著减少了中性粒细胞和巨噬细胞的浸润、促炎细胞因子MCP-1、TNF-α、IL-1β和IL-6的表达、促纤维化细胞因子IL-4、IL-13、TGF-β和P-Smad3的表达，同时增加了抗纤维化细胞因子IL-10的产生。在使用AM630的CB2R抑制组中观察到相反的结果。我们的研究表明，CB2R在骨骼肌挫伤修复过程中通过调节炎症反应来协调纤维化形成。
