Department of Orthopedic Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
Orthopedic-Traumatology Department, The 2nd Affiliated Hospital of Kunming Medical University, Kunming, 650101, Yunnan, China.
Spinal Cord. 2023 Aug;61(8):422-429. doi: 10.1038/s41393-023-00909-y. Epub 2023 Jul 4.
Animal experimental study.
Spinal cord injury (SCI) at or above the T6 level causes cardiovascular dysfunction. Maintaining cAMP levels with cAMP analogs can facilitate neurological recovery. In the present study, the effects of meglumine cyclic adenylate (MCA), a cAMP analog and approved cardiovascular drug, on cardiovascular and neurological recovery in acute T4-SCI in rats were investigated.
Hospital in Kunming, China.
Eighty rats were randomly allocated to five groups, and groups A-D received SCI: (A) a group administered MCA at 2 mg/kg/d iv qd, (B) a group administered dopamine at 2.5 to 5 μg/kg/min iv to maintain mean arterial pressure above 85 mm Hg, (C) a group administered atropine at 1 mg/kg iv bid, (D) a group receiving an equal volume of saline iv qd for 3 weeks after SCI and (E) a group undergoing laminectomy only. The cardiovascular and behavioral parameters of the rats were examined, and spinal cord tissues were processed for hematoxylin and eosin staining, Nissl staining, electron microscopy, and analysis of cAMP levels.
Compared with dopamine or atropine, MCA significantly reversed the decrease in cAMP levels in both myocardial cells and the injured spinal cord; improved hypotension, bradycardia and behavioral parameters at 6 weeks; and improved spinal cord blood flow and histological structure at 7 days post-SCI. The regression analysis suggested spinal cord motor-function improved as decreased heart rate and mean arterial pressure were stopped post-SCI.
MCA may be an effective treatment for acute SCI by sustaining cAMP-dependent reparative processes and improving post-SCI cardiovascular dysfunction.
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动物实验研究。
T6 及以上水平的脊髓损伤会导致心血管功能障碍。使用环磷酸腺苷类似物(cAMP 类似物)维持 cAMP 水平可以促进神经恢复。本研究旨在探讨环磷酸腺苷类似物、已批准的心血管药物,即 meglumine cyclic adenylate(MCA),对大鼠急性 T4-SCI 心血管和神经恢复的影响。
中国昆明的一家医院。
80 只大鼠随机分为 5 组,A-D 组接受脊髓损伤:(A)MCA 组,2mg/kg/d 静脉注射,每日 1 次;(B)多巴胺组,以 2.5 至 5μg/kg/min 的速度静脉滴注,以维持平均动脉压高于 85mmHg;(C)阿托品组,1mg/kg 静脉注射,每日 2 次;(D)损伤后每日接受等体积生理盐水静脉注射,共 3 周;(E)仅行椎板切除术。检测大鼠的心血管和行为参数,并对脊髓组织进行苏木精-伊红染色、尼氏染色、电镜检查和 cAMP 水平分析。
与多巴胺或阿托品相比,MCA 可显著逆转心肌细胞和损伤脊髓中 cAMP 水平的降低;改善损伤 6 周后的低血压、心动过缓和行为学参数;改善损伤后 7 天的脊髓血流和组织学结构。回归分析表明,脊髓运动功能的改善与损伤后停止的心率和平均动脉压降低有关。
MCA 通过维持 cAMP 依赖性修复过程和改善损伤后心血管功能障碍,可能成为急性脊髓损伤的有效治疗方法。
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