阿托伐他汀对脊髓损伤后神经细胞的自噬及运动神经功能恢复的影响

发布时间：2018-09-02 07:35

【摘要】：目的研究阿托伐他汀对脊髓损伤后神经细胞自噬活动的调控作用,以及对运动神经功能恢复的影响。方法将66只健康成年雄性SD大鼠随机分为三组:阿托伐他汀治疗组(Ato,n=22)、脊髓损伤模型组(SCI,n=22)、假手术组(Sham,n=22,仅接受椎板切除术);阿托伐他汀(5mg/kg)及作为对照的生理盐水在Allen,s法建立脊髓损伤模型后立即经腹腔注射,并且在脊髓损伤后第1、第二天相同时间点注射相同剂量阿托伐他汀及对照溶剂。改良Allen,s法建立脊髓损伤模型后,在损伤后第1、3、7、14、21、28、35、42天使用BBB评分观察不同处理组大鼠后肢运动功能恢复的情况;在手术后第7天运用Western blot分别检测自噬标记性蛋白(Beclin-1及LC3-B)及凋亡相关蛋白(caspase-9和caspase-3)的表达变化;并运用RT-PCR技术观察自噬标记性蛋白(Beclin-1和LC3-B)的基因表达变化情况;同时使用TUNEL染色观察脊髓损伤后脊髓前角运动神经元的凋亡变化情况。结果脊髓损伤后第14天及以后时间点,阿托伐他汀明显地促进了后肢运动神经功能的恢复(P0.05)。在脊髓损伤后第7天,Western blot及RT-PCR结果显示自噬标记性蛋白:Beclin-1和LC3-B蛋白及基因水平均明显地被阿托伐他汀所上调,意味着阿托伐他汀激活了脊髓损伤后神经细胞的自噬活动。此外,Western blot结果显示神经细胞凋亡相关蛋白:caspase-9和caspase-3表达水平明显地被阿托伐他汀抑制,相似的是,TUNEL染色结果也显示脊髓损伤后阿托伐他汀明显地抑制了脊髓前角运动神经元的凋亡活动。结论我们首次研究了脊髓损伤后阿托伐他汀和自噬的相关性,研究阐述了阿托伐他汀明显地增加了脊髓损伤后神经细胞的自噬活动,同时抑制神经细胞的凋亡,促进了运动功能的恢复,具有神经保护性作用。
[Abstract]:Aim to study the effects of Atto vastatin on the autophagy of nerve cells after spinal cord injury and on the recovery of motor nerve function. Methods Sixty-six healthy adult male SD rats were randomly divided into three groups: Atto vastatin treatment group (Ato,n=22), spinal cord injury model group (SCI,n=22), sham operation group (Sham,n=22, only underwent laminectomy), Atto vastatin (5mg/kg) and normal saline as control in Allen,s. Methods the spinal cord injury model was established immediately after intraperitoneal injection. The same dose of Atto vastatin and control solvent was injected at the first and second day after spinal cord injury. After the establishment of spinal cord injury model by modified Allen,s method, the recovery of motor function in hind limbs of rats in different treatment groups was observed by using BBB score on the 1st day after injury. The expression of autophagy marker protein (Beclin-1 and LC3-B) and apoptosis-related protein (caspase-9 and caspase-3) were detected by Western blot on the 7th day after operation, and the gene expression of Beclin-1 and LC3-B were observed by RT-PCR technique. TUNEL staining was used to observe the apoptosis of motor neurons in the anterior horn of spinal cord after spinal cord injury. Results at and after 14 days after spinal cord injury, Atto vastatin significantly promoted the recovery of motor nerve function in the hind limb (P0.05). On the 7th day after spinal cord injury, the results of Western blot and RT-PCR showed that the protein and gene levels of autophagy marker protein: Beclin-1 and LC3-B were significantly up-regulated by Atto vastatin, suggesting that Atto vastatin activated autophagy of neurons after spinal cord injury. In addition, the results of Western blot showed that the expression of neuronal apoptosis-related protein: caspase-9 and caspase-3 was significantly inhibited by Atto vastatin. Similarly, Tunel staining showed that Atto vastatin significantly inhibited the apoptosis of motor neurons in the anterior horn of spinal cord after spinal cord injury. Conclusion We studied for the first time the correlation between Atto vastatin and autophagy after spinal cord injury. We demonstrated that Atto vastatin significantly increased autophagy activity and inhibited neuronal apoptosis after spinal cord injury. It promotes the recovery of motor function and has neuroprotective effect.
【学位授予单位】：锦州医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R651.2

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