Department of Pediatrics, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA.
J Neuroimmune Pharmacol. 2013 Mar;8(1):274-86. doi: 10.1007/s11481-012-9419-3. Epub 2012 Nov 28.
Lumbar spinal stenosis (LSS) is the leading cause of morbidity and mortality worldwide. LSS pathology is associated with secondary injury caused by inflammation, oxidative damage and cell death. Apart from laminectomy, pharmacological therapy targeting secondary injury is limited. Statins are FDA-approved cholesterol-lowering drug. They also show pleiotropic anti-inflammatory, antioxidant and neuroprotective effects. To investigate the therapeutic efficacy of simvastatin in restoring normal locomotor function after cauda equina compression (CEC) in a rat model of LSS, CEC injury was induced in rats by implanting silicone gels into the epidural spaces of L4 and L6. Experimental group was treated with simvastatin (5 mg/kg body weight), while the injured (vehicle) and sham operated (sham) groups received vehicle solution. Locomotor function in terms of latency on rotarod was measured for 49 days and the threshold of pain was determined for 14 days. Rats were sacrificed on day 3 and 14 and the spinal cord and cauda equina fibers were extracted and studied by histology, immunofluorescence, electron microscopy (EM) and TUNEL assay. Simvastatin aided locomotor functional recovery and enhanced the threshold of pain after the CEC. Cellular Infiltration and demyelination decreased in the spinal cord from the simvastatin group. EM revealed enhanced myelination of cauda equina in the simvastatin group. TUNEL assay showed significantly decreased number of apoptotic neurons in spinal cord from the simvastatin group compared to the vehicle group. Simvastatin hastens the locomotor functional recovery and reduces pain after CEC. These outcomes are mediated through the neuroprotective and anti-inflammatory properties of simvastatin. The data indicate that simvastatin may be a promising drug candidate for LSS treatment in humans.
腰椎管狭窄症（LSS）是全球发病率和死亡率的主要原因。LSS 病理学与炎症、氧化损伤和细胞死亡引起的继发性损伤有关。除了椎板切除术，针对继发性损伤的药物治疗有限。他汀类药物是美国食品和药物管理局批准的降胆固醇药物。它们还具有多种抗炎、抗氧化和神经保护作用。为了研究辛伐他汀在 LSS 大鼠模型马尾压迫（CEC）后恢复正常运动功能的治疗效果，通过将硅胶凝胶植入硬膜外腔 L4 和 L6 来诱导大鼠 CEC 损伤。实验组用辛伐他汀（5mg/kg 体重）治疗，而受伤（载体）和假手术（假）组给予载体溶液。在 49 天内测量旋转棒上的潜伏期以评估运动功能，在 14 天内测定疼痛阈值。在第 3 天和第 14 天处死大鼠，提取和研究脊髓和马尾纤维的组织学、免疫荧光、电子显微镜（EM）和 TUNEL 检测。辛伐他汀有助于 CEC 后运动功能的恢复和疼痛阈值的提高。脊髓中的细胞浸润和脱髓鞘减少。EM 显示辛伐他汀组马尾神经髓鞘增强。TUNEL 检测显示辛伐他汀组脊髓中凋亡神经元的数量明显少于载体组。辛伐他汀可加速 CEC 后运动功能的恢复和减轻疼痛。这些结果是通过辛伐他汀的神经保护和抗炎特性介导的。该数据表明，辛伐他汀可能是治疗人类 LSS 的有前途的药物候选物。
