槲皮素促进小鼠脊髓损伤后轴突生长及功能恢复研究

Quercetin Promotes Axonal Growth and Functional Recovery after Spinal Cord Injury in Mice

目的评价槲皮素对小鼠脊髓损伤后轴突生长及功能恢复的影响。方法 C57BL/6雌性小鼠24只,随机分为2组,各12只。将2组小鼠T10节段施以完全性脊髓钳夹伤,治疗组分别于损伤前30 min、损伤后即刻、损伤后1-10 d每天1次腹腔注射槲皮素(50 mg/kg),对照组则腹腔注射等量0.9%氯化钠溶液。于损伤后14 d将BDA神经示踪剂注入小鼠皮层感觉运动区,示踪皮质脊髓束,组织切片复染GFAP标记损伤边界。通过荧光显微镜观察损伤区近段皮质脊髓束轴突退缩及再生情况。在术后当日及1、3、7、14、28 d,采用BMS(Basso mouse scale)量表评价小鼠后肢及躯干运动功能。结果损伤后第28天,与对照组相比,槲皮素治疗组轴突出芽量化比值上升;神经轴缩球量化比值下降;传导束到损伤边缘距离下降,差异均有统计学意义(P<0.01)。行为学评估表明槲皮素显著提高小鼠BMS评分(P<0.01),第28天治疗组BMS显著高于对照组(P<0.01)。结论槲皮素可明显促进脊髓损伤后轴突出芽,减少回缩,促进运动功能恢复。

Objective To evaluate the effect of quercetin on axonal growth and functional recovery in mice after spinal cord injury. Methods Twenty-four C57BL/6 female mice were randomly and evenly divided into two groups. Complete compression injury at the spinal cords of T10 was induced in both groups . The mice in therapeutic group were administered with quercetin （50 mg/kg） while control group received the same dose of saline by intraperitoneal injection at 30rain before injury, and immediately after injury, and then administered once a day from 1 to 10 days post-injury. The mice in control group received the same dose of saline with an equally long duration. Biotinylated dextran amine （BDA） was injected into the sensorimotor cortex at 14 days post-injury to trace the corticospinal tract （CST）. Counterstaining was performed with glial fibrillary acidic protein （GFAP） to label the lesion boundary. The CST retraction and pullulation were observed under a fluorescent microscope. BMS was performed to assess motor functional recovery at 1,3, 7, 14 and 28 days post-injury. Results Compared with control group, the ratio of total labeled sprouts/axons was significantly increased, the ratio of total labeled retraction bulbs/axons decreased, and the distance of the bundle to lesion border decreased after quercetin treatment at 28 days post-injury. The BMS scores were also significantly improved in therapeutic group （ P〈0.01 ）. Conclusion Quercetin can promote axonal pulluahion, prevent axonal retraction and improve motor functional recovery after spinal cord injury in mice.