Liao Jingwu, Xie Jingming, Lin Daqiang, Lu Ning, Guo Limin, Li Weiqiang, Pu Bo, Yang Yang, Yang Zhenlong, Zhang Ying, Song Yueming
Department of Orthopaedic Surgery, The 2nd Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650031, P.R. China.
Department of Orthopaedic Surgery, Hospital of Integrated Traditional and Western Medicine, Dazhou, Sichuan 635000, P.R. China.
Mol Med Rep. 2014 Sep;10(3):1225-30. doi: 10.3892/mmr.2014.2352. Epub 2014 Jun 25.
Elevation of intracellular cyclic adenosine monophosphate (cAMP) levels facilitates recovery following spinal injury by suppressing secondary pathology and promoting axonal regeneration. However, this treatment strategy is limited by lack of effective and tolerable clinical agents. The present study examined the effects of meglumine cyclic adenylate (MCA) on neurological recovery, cAMP concentration, adenylate cyclase 3 (AC3) activity and phosphodiesterase 4D (PDE4D) activity during early stage acute spinal cord injury (SCI) in rats. A total of 48 Sprague‑Dawley rats were randomly assigned to groups A, B or C, each consisting of 16 animals. SCI was induced by Allen's method using a 7 g x 3 cm extradural weight‑drop impact on spinal cord segment T11. A total of 30 min following SCI, group A received a single 30 mg/kg‑bw i.p. dose of methylprednisolone, group B received 2 mg/kg‑bw i.p. MCA daily for seven days and group C were administered an equal volume of normal saline. Seven days following SCI, the spinal cord samples from eight rats per group were obtained to measure the cAMP concentration, and the activities of AC3 and PDE4D. The remaining eight rats per group were used for behavioral assessments using the inclined plane stability test and Gale scale for up to six weeks post‑SCI. The drug‑treated groups A and B had higher cAMP concentrations and AC3 activities but lower PDE4D activities at the lesion sites, as well as superior behavioral scores post‑SCI compared with the vehicle‑treated group C (P<0.05). Furthermore, cAMP was higher in group B than in group A (P<0.05). It was concluded that MCA may serve as an effective SCI treatment by activating AC3 and suppressing PDE4D.
细胞内环磷酸腺苷（cAMP）水平的升高通过抑制继发性病理变化和促进轴突再生，有助于脊髓损伤后的恢复。然而，这种治疗策略受到缺乏有效且可耐受的临床药物的限制。本研究考察了环磷腺苷葡胺（MCA）对大鼠早期急性脊髓损伤（SCI）期间神经功能恢复、cAMP浓度、腺苷酸环化酶3（AC3）活性和磷酸二酯酶4D（PDE4D）活性的影响。总共48只Sprague-Dawley大鼠被随机分为A、B或C组，每组16只动物。采用Allen法，用7 g×3 cm硬膜外重物坠落撞击脊髓T11节段诱导SCI。SCI后30分钟，A组腹腔注射单次剂量30 mg/kg体重的甲基强的松龙，B组每天腹腔注射2 mg/kg体重的MCA，共7天，C组给予等体积的生理盐水。SCI后7天，每组取8只大鼠的脊髓样本测量cAMP浓度、AC3和PDE4D的活性。每组其余8只大鼠用于在SCI后长达6周的时间内，使用斜面稳定性试验和盖尔量表进行行为评估。与溶剂对照组C相比，药物治疗组A和B在损伤部位的cAMP浓度和AC3活性较高，但PDE4D活性较低，SCI后的行为评分也较高（P<0.05）。此外，B组的cAMP高于A组（P<0.05）。得出的结论是，MCA可能通过激活AC3和抑制PDE4D而成为一种有效的SCI治疗方法。
