腺苷治疗大鼠脊髓损伤的初步研究

Adenosine in treatment of rats with spinal cord injury

目的 通过观察大鼠脊髓损伤后内源性细胞外腺苷含量的变化以及外源性腺苷对脊髓损伤后脊髓组织细胞外钙离子和神经功能的影响 ,探讨腺苷在脊髓继发性损伤中的作用。 方法 SD大鼠 5 8只 ,制作成T13 脊髓腹侧压迫模型 ,用微透析技术每 2 0min连续收集脊髓损伤后脊髓组织细胞外液 ,用高效液相色谱仪紫外检测法检测细胞外液腺苷的含量 ;伤前 15min蛛网膜下腔给予非特异性腺苷受体激动剂 2 氯腺苷 ,伤后立即开始每 10min连续收集脊髓组织细胞外液 ,用原子吸收光谱分析法测定收集液中的钙离子浓度 ;于伤后 2 4h观察神经功能评分、倾斜平面临界角和组织学变化。 结果 脊髓损伤后腺苷浓度立即显著升高 ,至 1h达最高峰 ,且升高幅度与伤情成正比 ,2h降为基础水平 ;大剂量 2 氯腺苷蛛网膜下腔注射能显著抑制脊髓损伤后细胞外钙离子的下降 ,改善脊髓损伤后的神经功能。 结论 腺苷参与了脊髓继发性损伤的病理过程 。

Objective To observe the changes of endogenous extracellular adenosine after spinal cord injury (SCI) to rats and the effect of exogenous adenosine on extracellular calcium after SCI and post injury neurolo gical function. Methods A ventral compression injury model of T13 spinal cord was used, and the extracellular fluids were collected consecutively every 20 minutes after injury by using microdialysis. Adenosine in the samples was analyzed using high pressure liquid chromatography (HPLC) with u.v. detection. The rats received different doses of 2 chloroadenosine (2 CADO), a nonspecific agonist of adenosine receptors, by intrathecal injection 15 minutes before injury. The extracellular fluid was collected every 10 minutes immediately after injury and the calcium was measured using atomic absorption spectrophotometer. Neurological function score, inclined plane angle, and histology were observed 24 hours after injury. Results A significant increase of adenosine was found immediately after spinal cord injury. The concentration of adenosine peaked at one hour after injury and dropped down to the basal level. There was a positive relation between the increase of adenosine and the severity of SCI. High dose of 2 CADO can significantly significantly inhibit the decrease of extracellular calcium and improve the neurological function of injured rats. Conclusions Adenosine could involve the pathological process of secondary spinal cord injury and might play a protective role in SCI.