氯化血红素诱导脊髓组织脑红蛋白高表达对脊髓损伤大鼠运动功能的保护作用
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摘要
目的探讨氯化血红素(Hemin)诱导脊髓组织脑红蛋白高表达对脊髓损伤大鼠运动功能的保护作用。方法健康雄性SD大鼠90只随机分为对照组(假手术组)、手术组、氯化血红素处理组(造模后腹腔注射氯化血红素溶液)。采用大鼠后肢功能BBB评分评价各组大鼠实验后1 d、3 d、7 d、14 d、28 d、56 d时的运动功能差异。结果大鼠脊髓组织Ngb免疫组化结果显示初中期氯化血红素处理组脊髓组织Ngb阳性细胞数最高,手术组次之,对照组最低。其中,Hemin处理组与手术组阳性细胞密度高于对照组。BBB评分结果显示术后对照组各时间点的评分最高;手术组得分最低,手术组的表现不仅从评分上明显低于另外两组,且恢复速度也明显低于Hemin处理组,Hemin处理组恢复速度为三组中最快。结论氯化血红素诱导脊髓损伤大鼠脊髓组织内脑红蛋白高表达,改善了脊髓损伤大鼠的运动评分并提高了脊髓损伤后运动功能的恢复速度。
Objective To investigate the protective effects of high expression of neuroglobin induced by Hemin on motor functions of rats with spinal cord injuries. Methods Healthy male SD rats were randomly divided into three groups, control group(sham operation group), operation group and Hemin treatment group(intraperitoneal injection of Hemin solutions after molding). Rat hindlimb function BBB scale was used to evaluate the difference in motor functions among rats from the three groups at 1 d, 3 d, 7 d,14 d, 28 d, 56 d after experiment. Results The results of Ngb immunohistochemistry of rats spinal cord tissue showed that at the early and middle stages after operation, the number of Ngb positive cells was highest in the Hemein treatment group, followed by the operation group and the lowest in the control group. Postoperative BBB score was highest in the control group at each time point, and lowest in operation group. Hemin treatment group had the fastest recovery rate. Conclusion Hemin treatment improves the motor functions of rats with spinal cord injuries and accelerates the motor function recovery after spinal cord injuries.
Objective To investigate the protective effects of high expression of neuroglobin induced by Hemin on motor functions of rats with spinal cord injuries. Methods Healthy male SD rats were randomly divided into three groups, control group(sham operation group), operation group and Hemin treatment group(intraperitoneal injection of Hemin solutions after molding). Rat hindlimb function BBB scale was used to evaluate the difference in motor functions among rats from the three groups at 1 d, 3 d, 7 d,14 d, 28 d, 56 d after experiment. Results The results of Ngb immunohistochemistry of rats spinal cord tissue showed that at the early and middle stages after operation, the number of Ngb positive cells was highest in the Hemein treatment group, followed by the operation group and the lowest in the control group. Postoperative BBB score was highest in the control group at each time point, and lowest in operation group. Hemin treatment group had the fastest recovery rate. Conclusion Hemin treatment improves the motor functions of rats with spinal cord injuries and accelerates the motor function recovery after spinal cord injuries.
引文
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14 Liu ZF,Zhang X,Qiao YX,et al.Neuroglobin protects cardiomyocytes against apoptosis and cardiac hypertrophy induced by isoproterenol in rats[J].Int J Clin Exp Med,2015,8(4):5351-5360.
15 Raida Z,Hundahl CA,Nyengaard JR,et al.Neuroglobin Over Expressing Mice:Expression Pattern and Effect on Brain Ischemic Infarct Size[J].PLoS ONE,2013,8(10):e76565.
16 Luyckx E,Van Leuven W,Andre D,et al.Loss of Neuroglobin Expression Alters Cdkn1a/Cdk6-Expression Resulting in Increased Proliferation of Neural Stem Cells[J].Stem Cells Dev,2018,27(6):378-390.
17 Ragy M,Ali F,Ramzy MM.Effect of Hemin on Brain Alterations and Neuroglobin Expression in Water Immersion Restraint Stressed Rats[J/OL].https://www.hindawi.com/journals/scientifica/2016/7825396.
2 Zhu Y,Sun Y,Jin K,et al.Hemin induces neuroglobin expression in neural cells[J].Blood,2002,100(7):2494-2498.
3 Baez E,Echeverria V,Cabezas R,et al.Protection by Neuroglobin Expression in Brain Pathologies[J].Front Neurol,2016,7:146.
4 Yu Z,Poppe JL,Wang X.Mitochondrial mechanisms of neuroglobin's neuroprotection[J/OL].https://www.hindawi.com/journals/omcl/2013/756989.
5尚爱加,周定标,孟祥辉,等.脑红蛋白在成年大鼠脊髓中的分布[J].解剖学报,2006,37(5):492-494.
6 Fan R,Yu T,Lin JL,et al.Remote ischemic preconditioning improves post resuscitation cerebral function via overexpressing neuroglobin after cardiac arrest in rats[J].Brain Res,2016,1648(Pt A):345-355.
7 Liu Y,Li B,Li Q,et al.Neuroglobin up-regulation after ischaemic pre-conditioning in a rat model of middle cerebral artery occlusion[J].Brain Inj,2015,29(5):651-657.
8 Ascenzi P,di Masi A,Leboffe L,et al.Neuroglobin:From structure to function in health and disease[J].Mol Aspects Med,2016,52:1-48.
9 Lan WB,Lin JH,Chen XW,et al.Overexpressing neuroglobin improves functional recovery by inhibiting neuronal apoptosis after spinal cord injury[J].Brain Res,2014,1562:100-108.
10 Li W,Wu Y,Ren C,et al.The activity of recombinant human neuroglobin as an antioxidant and free radical scavenger[J].Proteins,2011,79(1):115-125.
11熊春翔,宗少晖,曾高峰,等.大鼠Allen's脊髓损伤模型的建立及评价[J].广西医科大学学报,2011,28(2):215-217.
12 Xue L,Chen H,Lu K,et al.Clinical significance of changes in serum neuroglobin and HIF-1αconcentrations during the earlyphase of acute ischemic stroke[J].J Neurol Sci,2017,375:52-57.
13 Cabezas R,Baez-Jurado E,Hidalgo-Lanussa O,et al.Growth Factors and Neuroglobin in Astrocyte Protection Against Neurodegeneration and Oxidative Stress[J/OL].https://link.springer.com/article/10.1007%2Fs12035-018-1203-9.
14 Liu ZF,Zhang X,Qiao YX,et al.Neuroglobin protects cardiomyocytes against apoptosis and cardiac hypertrophy induced by isoproterenol in rats[J].Int J Clin Exp Med,2015,8(4):5351-5360.
15 Raida Z,Hundahl CA,Nyengaard JR,et al.Neuroglobin Over Expressing Mice:Expression Pattern and Effect on Brain Ischemic Infarct Size[J].PLoS ONE,2013,8(10):e76565.
16 Luyckx E,Van Leuven W,Andre D,et al.Loss of Neuroglobin Expression Alters Cdkn1a/Cdk6-Expression Resulting in Increased Proliferation of Neural Stem Cells[J].Stem Cells Dev,2018,27(6):378-390.
17 Ragy M,Ali F,Ramzy MM.Effect of Hemin on Brain Alterations and Neuroglobin Expression in Water Immersion Restraint Stressed Rats[J/OL].https://www.hindawi.com/journals/scientifica/2016/7825396.