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Agmatine Modulates the Phenotype of Macrophage Acute Phase after Spinal Cord Injury in Rats.
Experimental Neurobiology ( IF 1.8 ) Pub Date : 2017-10-16 , DOI: 10.5607/en.2017.26.5.278
Jae Hwan Kim 1, 2, 3 , Jae Young Kim 3 , Chin Hee Mun 4 , Minah Suh 1, 2 , Jong Eun Lee 3, 5
Affiliation  

Agmatine is a decarboxylated arginine by arginine decarboxylase. Agmatine is known to be a neuroprotective agent. It has been reported that agmatine works as a NMDA receptor blocker or a competitive nitric oxide synthase inhibitor in CNS injuries. In spinal cord injury, agmatine showed reduction of neuropathic pain, improvement of locomotor function, and neuroprotection. Macrophage is a key cellular component in neuroinflammation, a major cause of impairment after spinal cord injury. Macrophage has subtypes, M1 and M2 macrophages. M1 macrophage induces a pro-inflammatory response, but M2 inspires an anti-inflammatory response. In this study, it was clarified whether the neuroprotective effect of agmatine is related with the modulation of macrophage subdivision after spinal cord injury. Spinal cord injury was induced in rats with contusion using MASCIS. Animals received agmatine (100 mg/kg, IP) daily for 6 days beginning the day after spinal cord injury. The proportion of M1 and M2 macrophages are confirmed with immunohistochemistry and FACS. CD206+ & ED1+ cells were counted as M2 macrophages. The systemic treatment of agmatine increased M2 macrophages caudal side to epicenter 1 week after spinal cord injury in immunohistochemistry. M2 macrophage related markers, Arginase-1 and CD206 mRNA, were increased in the agmatine treatment group and M2 macrophage expressing and stimulated cytokine, IL-10 mRNA, also was significantly overexpressed by agmatine injection. Among BMPs, BMP2/4/7, agmatine significantly increased only the expression of BMP2 known to reduce M1 macrophage under inflammatory status. These results suggest that agmatine reduces impairment after spinal cord injury through modulating the macrophage phenotype.

中文翻译:

胍丁胺调节大鼠脊髓损伤后巨噬细胞急性期的表型。

胍丁胺是通过精氨酸脱羧酶的脱羧精氨酸。已知胍丁胺是神经保护剂。据报道,胍丁胺在中枢神经系统损伤中起NMDA受体阻滞剂或竞争性一氧化氮合酶抑制剂的作用。在脊髓损伤中,胍丁胺显示出神经性疼痛的减轻,运动功能的改善和神经保护作用。巨噬细胞是神经炎症中的关键细胞成分,神经炎症是脊髓损伤后损害的主要原因。巨噬细胞具有亚型,M1和M2巨噬细胞。M1巨噬细胞诱导促炎反应,但是M2激发抗炎反应。在这项研究中,澄清了胍丁胺的神经保护作用是否与脊髓损伤后巨噬细胞细分的调节有关。使用MASCIS在挫伤大鼠中诱发脊髓损伤。在脊髓损伤后的第二天开始,动物每天接受胍丁胺(100 mg / kg,IP)治疗,为期6天。M1和M2巨噬细胞的比例已通过免疫组化和FACS确认。CD206+和ED1 +细胞计数为M2巨噬细胞。免疫组化研究显示,胍丁胺的全身治疗可使脊髓损伤后1周的M2巨噬细胞尾侧增加至震中。胍丁胺治疗组中M2巨噬细胞相关标志物Arginase-1和CD206 mRNA升高,而注射胍丁胺后M2巨噬细胞表达和刺激的细胞因子IL-10 mRNA也明显过量表达。在BMP,BMP2 / 4/7,胍丁胺中,胍丁胺仅显着增加已知在炎性状态下可减少M1巨噬细胞的BMP2的表达。这些结果表明,胍丁胺可通过调节巨噬细胞表型减少脊髓损伤后的损伤。
更新日期:2020-08-21
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