利拉鲁肽通过抑制线粒体凋亡途径对大鼠脊髓损伤的保护作用  

Neuroprotective effects of Liraglutide in rat model of spinal cord injury via inhibiting mitochondrial apoptotic pathway

作　　者：李昊天[1] 赵兴长 李刚[1] 王继权[1] 孙平[1] 吕刚[1] 范仲凯[1] 

机构地区：[1]辽宁医学院附属第一医院骨科,锦州121001

出　　处：《神经解剖学杂志》2015年第4期439-444,共6页Chinese Journal of Neuroanatomy

基　　金：国家自然科学基金(81272074);辽宁省高等学校优秀人才支持计划项目(LJQ2014091);辽宁医学院校长基金(AH2014012)

摘　　要：目的:研究利拉鲁肽注射液对大鼠脊髓损伤(spinal cord injury,SCI)后线粒体氧化损伤、细胞色素C(Cyt-C)、caspase-3及细胞凋亡的影响。方法:将36只健康SD大鼠随机分为假手术组(Sham组)、脊髓损伤组(SCI组,生理盐水50μg/kg,腹腔注射)、利拉鲁肽组(50μg/kg,腹腔注射),每组12只。采用Allen’s法制作SCI模型,假手术组仅行椎板切除,其余二组行椎板切除并打击。模型建立24 h后取受损脊髓,提取脊髓组织线粒体,分别检测丙二醛(MDA)、谷胱甘肽(GSH)的含量、Cyt-C与caspase-3表达,JC-1法测定线粒体膜电位的变化,TUNEL染色法检测细胞的凋亡情况。结果:利拉鲁肽组较SCI模型组脊髓组织线粒体中GSH的含量明显有所升高,而MDA的含量明显降低(P<0.01),JC-1法示利拉鲁肽组大鼠线粒体膜电位较SCI模型组明显有所提高(P<0.01)。Western Blot法和TUNEL法分别显示利拉鲁肽组大鼠脊髓内Cyt-C、caspase-3的表达和细胞凋亡数较SCI模型组明显有所减少(P<0.01)。结论:利拉鲁肽能够改善SCI后线粒体氧化损伤,保护线粒体膜电位,减少Cyt-C释放,降低caspase-3表达,抑制细胞凋亡,对SCI起到保护作用。Objective： To investigate the effect of Liraglutide on mitochondrial oxidative damage, Cyt-C, caspase-3 and apoptosis in rat model of spinal cord injury （SCI）. Methods： Thirty-six adult SD rats were randomly divided into 3 groups （n = 12） ： Sham operation group （Sham group）, spinal cord injury group （SCI group, received 50 μg/kg saline injection intraperitoneally） and Liraglutide group （received 50 μg/kg Liraglutide injection intraperitoneally）. Spinal cord injury model was established using Allen＇s method. Sham group only received laminectomy; the others received laminec- tomy and spinal trauma. Rats were sacrificed at 24 h after SCI. The contents of malondialdehyde （MDA） and glutathione （GSH） were detected and the expressions of Cyt-C and caspase-3 protein in the cytoplasm were detected by Western Blot assay. Mitochondrial membrane potential was measured using JC-1. The apoptosis was assessed by TUNEL staining. Results： In spinal cord of rats, GSH level was significantly elevated and MDA level was significantly decreased in the Li- raglutide group compared with SCI group （ P 〈 0.01 ）. Meanwhile, mitochondrial membrane potential increased signifi- cantly compared with SCI group （P 〈 0.01 ）. Western Blot results showed that the expression of Cyt-C and caspase-3 in Liraglutide group was lower than that in SCI group （P 〈 0.01 ）. Finally, TUNEL staining results showed that the apopto- sis in Liraglutide group was reduced significantly compared with SCI group （P 〈 0.01 ）. Conclusion： Liraglutide shows a neuroprotective effect in the rat model of SCI via reducing oxidative stress, preserving mitochondrial membrane potential, attenuating the Cyt-C release and activation of apoptotic molecules and inhibiting apoptosis in the spinal cord.

关 键 词：脊髓损伤 利拉鲁肽 线粒体 氧化应激 细胞凋亡 大鼠 

分 类 号：R651.2[医药卫生—外科学]