Effect of Liraglutide on neuronal autophagy and movements recovery after spinal cord injury in rats
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摘要: 目的 探讨利拉鲁肽注射液（Liraglutide）对急性脊髓损伤（spinal cord injury，SCI）后神经细胞的保护作用及其可能机制。 方法 54只SD大鼠随机分成假手术组（Sham组）、脊髓损伤组（SCI组，损伤后立即腹腔注射0.9%氯化钠注射液50μg/kg）和治疗组（Liraglutide组，损伤后立即腹腔注射利拉鲁肽50μg/kg），每组18只，Allen法建立大鼠脊髓损伤模型，于损伤后3 d取脊髓组织，Western blot检测LC3-Ⅱ、Caspase-3表达，免疫荧光双标染色观察神经元自噬表达水平、神经细胞凋亡情况；于损伤后1 d、3 d、7 d分别进行Basso Beattle Bresnahan （BBB）运动评分。 结果 与Sham组相比，SCI组LC3-Ⅱ、Caspase-3表达、自噬阳性神经细胞数目、神经细胞凋亡数目均增多（P< 0.01），BBB评分显著降低（P< 0.01）；Liraglutide组与SCI组相比，LC3-Ⅱ显著增多，Caspase-3表达降低（P< 0.01）；免疫荧光双标染色示自噬阳性细胞数目明显增多（P< 0.01）；神经元凋亡双标染色法示神经凋亡细胞数目明显减少（P< 0.01）；BBB评分在3 d与7 d时有显著提高（P< 0.01）。 结论 利拉鲁肽增强大鼠脊髓损伤后神经细胞自噬，降低凋亡相关蛋白表达，减少神经细胞凋亡，促进大鼠运动功能恢复，对脊髓损伤具有保护作用。Abstract: Objective To explore the neuroprotective effect and possible mechanism of Liraglutide in the rat model of spinal cord injury (SCI). Methods Fifty-four SD rats were randomly divided into three groups:sham operation group (n=18), spinal cord injury (SCI) group (immediately received 50μg/kg saline injection intraperitoneally after injury, n=18) and Liraglutide group (immediately received 50μg/kg Liraglutide injection intraperitoneally after injury, n=18). Spinal cord injury model was established using Allen's method. The rats were sacrificed and the spinal cord tissue were taken out 3 days after injury. Western blot was used to analyze the LC3-Ⅱ and caspase-3 expression. Immunofluorescent double labeling was used to detect the autophagy positive neurons and neuronal apoptosis. Finally, behavioral assessment with Basso Beattle Bresnahan locomotor rating scale (BBB) was done at 1 d, 3 d and 7 d after injury. Results Compared with sham group, the expression of LC3-Ⅱ, the level of caspase-3 and the number of autophagy positive neurons and neuronal apoptosis increased significantly in SCI group (P< 0.01), while the BBB score decreased significantly (P< 0.01). Furthermore, compared with SCI group, Western blot showed that the expression of LC3-Ⅱincreased while the level of caspase-3 decreased in Liraglutide group (P< 0.01). Immunofluorescent double labeling showed that the number of autophagy positive neurons enhanced significantly (P< 0.01) and the neuronal apoptosis in Liraglutide group reduced significantly compared with SCI group (P< 0.01). Finally, behavioral assessment showed that animals in Liraglutide group achieved significant increase in BBB score on 3 d and 7 d (P< 0.01). Conclusion Liraglutide promotes neuronal autophagy, decreases neuronal apoptosis and improves the locomotor function after SCI. Liraglutide may be a new candidate for clinical application in the treatment of SCI.
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Keywords:
- spinal cord injury /
- Liraglutide /
- autophagy /
- apoptosis
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