摘要
目的:探究硫酸软骨素酶ABC(Ch ABC)联合脊髓康对大鼠脊柱脊髓损伤后的神经功能恢复及TGF-β1、HIF-1α、Nogo-NgR信号通路的影响。方法:60只大鼠随机分为4组,分别为对照组、模型组、Ch ABC组和Ch ABC+脊髓康。使用Allen’s法建立大鼠脊柱脊髓损伤模型。Basso Beattie Bresnah-an(评分)和体感诱发电位(sEP)检测评估脊髓神经功能。使用RT-qPCR检测mRNA水平,Westernblot检测蛋白水平。结果:建模后大鼠BBB评分显著降低(P<0.05),干预后3组的BBB评分均有提高,其中Ch ABC+脊髓康组BBB评分显著高于Ch ABC组(P<0.05)。建模后大鼠SEP显著升高(P<0.05),干预后3组的BBB评分均有降低,其中Ch ABC+脊髓康组BBB评分显著低于Ch ABC组(P<0.05)。干预后Ch ABC组和Ch ABC+脊髓康组TGF-β1显著高于模型组,HIF-1α显著低于模型组(P<0.05)。且干预后Ch ABC+脊髓康组TGF-β1的水平显著高于Ch ABC组而HIF-1α显著低于Ch ABC组(P<0.05)。干预后Ch ABC组和Ch ABC+脊髓康组Nog-oNgR通路表达水平显著低于模型组(P<0.05),并且干预后Ch ABC+脊髓康组的Nogo-A、NgR、LINGO-1表达水平显著低于ChABC组(P<0.05)。结论:ChABC联合脊髓康具有更强的促进神经功能恢复的作用,脊髓康的联合使用可进一步抑制HIF-1α水平而提高TGF-β1水平,提高预后促进脊柱愈合。并且联合用药的作用机制可能与其具有抑制Nogo-NgR信号通路促进神经元生长的作用有关。
Objective:To explore the effects of chondroitinase ABC(Ch ABC)combined with spinal cord on neurological recovery and TGF-β1,HIF-1αand Nog-oNgR signaling pathways after spinal cord injury in rats.Methods:Sixty rats were randomly divided into 4 groups:control group,model group,Ch ABC group and Ch ABC+spinal cord.A rat spinal cord injury model was established using the Allen's method.Spinal nerve function was assessed by Basso Beattie Bresnahan(score)and somatosensory evoked potential(sEP)assays.mRNA levels were detected using RT-qPCR.Western blot was used to detect protein levels.Results:After modeling,the BBB scores of the rats were significantly decreased(P<0.05).After the intervention,the BBB scores of the three groups were improved.The BBB scores of the Ch ABC+spinal cord group were significantly higher than those of the Ch ABC group(P<0.05).After modeling,the SEP of the rats was significantly increased(P<0.05).After the intervention,the BBB scores of the three groups were decreased.The BBB scores of the Ch ABC+spinal cord group were significantly lower than those of the Ch ABC group(P<0.05).The TGF-β1 in the Ch ABC group and the Ch ABC+spinal group was significantly higher than that in the model group,and the HIF-1αwas significantly lower than the model group(P<0.05).The level of TGF-β1 in Ch ABC+spinal cord group was significantly higher than that in Ch ABC group and HIF-1αwas significantly lower than that in Ch ABC group(P<0.05).After treatment,the expression levels of Nog-oNgR pathway in Ch ABC group and Ch ABC+spinal cord group were significantly lower than those in model group(P<0.05),and the expression levels of Nogo-A,NgR and LINGO-1 in Ch ABC+spinal cord group were significant after intervention.Lower than Ch ABC group(P<0.05).Conclusion:ChABC combined with spinal cord has a stronger role in promoting the recovery of neurological function.The combination of spinal cord can further inhibit the level of HIF-1αand increase the level of TGF-β1,and improve the prognosis to promote spinal healing.And the mechanism of action of the combination may be related to its role in inhibiting the growth of neurons by the Nogo-NgR signaling pathway.
作者
黄贻泽
彭琳
张戈
HUANG Yi-ze;PENG Lin;ZHANG Ge(Department of Pain,Yilong People's Hospital,Yilong,Sichuan 637600;Department of Orthopedics,The Affiliated Hospital of Southwest Medical University,Luzhou Sichuan 646000;Department of orthopedics,Luzhou people's Hospital,Luzhou Sichuan 646000)
出处
《海南医学院学报》
CAS
2019年第2期94-98,共5页
Journal of Hainan Medical University
基金
四川省教育厅课题(17PJ204)
四川省科技厅重点项目(2015JY0224)~~