Limaprost Alfadex, a Prostaglandin E1 Derivative, Prevents Deterioration of Forced Exercise Capability in Rats with Chronic Compression of the Spinal Cord

Limaprost Alfadex, a Prostaglandin E1 Derivative, Prevents Deterioration of Forced Exercise Capability in Rats with Chronic Compression of the Spinal Cord
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DOI:
10.1097/brs.0b013e3181e878a1
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发表时间:
2011-05-15
期刊:
影响因子:
3
通讯作者:
Kim, Phyo
Kim, Phyo
中科院分区:
医学2区
文献类型:
--
作者:
Kurokawa, Ryu;Nagayama, Eriko;Kim, Phyo

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研究设计。目的:基础动物研究。脊髓型颈椎病是老年人的常见疾病,通常需要手术治疗。为了探索药物治疗的可能性,在大鼠慢性脊髓压迫模型上,尝试了具有血管扩张和抗血小板作用的前列腺素E1衍生物利马前列素α-地塞米松。利马前列素增加马尾神经血流量,改善腰椎管狭窄动物模型的运动功能。方法:将42只大鼠随机分为4组:A组为无永久性脊髓压迫的假手术组,给予蒸馏水5mL/kg,2次/d;B组为假手术组,给予利马前列素300 mg/kg/d,2次/d;C组为脊髓压迫组,接受药物治疗;D组为脊髓压迫组,接受药物治疗。在C5-C6椎板下植入一层通过吸收水分而膨胀的薄层聚亚安酯,以产生脐带压缩。对于假手术,立即将床单取下。在旋转跑步机上重复运动试验,直到手术后26周,然后处死动物,并采集脊髓进行运动神经元计数。术后2周,A、B、C、D组的跑台耐力分别为497.7+/-2.3s、434.5+/-65.5s、423.1+/-33.0s和480.5+/-19.5s。26周时分别为497.7+/-2.3、421.2+/-78.8、21.3+/-11.7、441.3+/-40.4(P<0.0001为C组下降,多指标校正多变量方差分析)。运动神经元计数A、B、C、D组分别为38.3+/-3.6、38.2+/-2.6、32.6+/-1.9、36.2+/-2.3(P=0.34)。利马前列素可预防慢性颈髓压迫大鼠强迫运动能力的下降。
Study Design. Basic animal research.Objective. Cervical spondylotic myelopathy is a common condition among elderly and often treated by surgery. To explore possibility of pharmacologic treatment, limaprost alfadex, a prostaglandin E1 derivative with vasodilatory and antiplatelet action, was tried in a rat chronic spinal cord compression model.Summary of Background Data. Limaprost increased the blood flow of cauda equina and improved motor functions in animal models of lumbar stenosis. The drug is clinically used to treat neurogenic intermittent claudication.Methods: Forty-two rats were allocated to four groups: (A) sham operation without permanent cord compression, given 5 mL/kg of distilled water twice a day (n = 6); (B) sham operation, receiving 300 mu g/kg limaprost twice a day (n = 6); (C) cord compression, receiving the vehicle (n = 15); and (D) cord compression receiving the drug (n = 15). A thin polyurethane sheet that expands by absorbing water was implanted under the C5-C6 laminae to produce cord compression. For sham operation, the sheet was immediately removed. Exercise tests were repeated on a rotating treadmill until 26 weeks after surgery, and then the animals were killed and the spinal cord harvested for motor neurons counts.Results. Treadmill endurance (seconds, mean +/- standard error of mean) 2 weeks after surgery was 497.7 +/- 2.3, 434.5 +/- 65.5, 423.1 +/- 33.0, and 480.5 +/- 19.5 in groups A, B, C, and D, respectively. At 26th week, the duration was 497.7 +/- 2.3, 421.2 +/- 78.8, 21.3 +/- 11.7, and 441.3 +/- 40.4 (P < 0.0001 for the decrease in C group, multivariate analysis of variance with correction for multiple measures.) The motor neuron counts were 38.3 +/- 3.6, 38.2 +/- 2.6, 32.6 +/- 1.9, and 36.2 +/- 2.3 in groups A, B, C, and D (P = 0.34), respectively.Conclusion. Limaprost alfadex prevented decline of forced locomotion capability in rats with chronic compression of the cervical cord.