大鼠脊髓骶2节段损伤后脊髓DRD1表达的变化
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摘要
目的:研究脊髓损伤(spinalcordinjury,SCI)后大鼠尾部的痉挛特征和脊髓多巴胺D1受体(dopamine receptor-1,DRD1)表达的变化。方法:成年雄性Wistar大鼠随机分为假手术(Sham)组和SCI组。SCI组大鼠第2骶髓(S2)节段全横断,分别于术后2d、7d、14d、30d、60d进行大鼠尾部痉挛评分;两组大鼠均于术后60d取骶尾段脊髓,采用免疫荧光法检测大鼠脊髓灰质DRD1的表达。结果:SCI组大鼠术后2d、7d、14d、30d、60d时尾部痉挛评分分别为0、1.10±0.28、1.32±0.85、2.50±0.53、4.15±0.36分。大鼠脊髓骶尾段灰质的背角(dorsal horn,DH)、中间带(intermediatezone,IMZ)、腹角(ventralhorn,VH)均可见DRD1表达。SCI组大鼠灰质DH、IMZ、VH中DRD1表达的光密度值均明显低于Sham组大鼠,组间差异有显著性(P<0.05)。结论:SCI后脊髓DRD1表达降低可能与大鼠尾部痉挛的发生发展有关。
Objective: To study the spasticity of rat tail and the changes of dopamine receptor-1(DRD1) expression in spinal cord after spinal cord injury(SCI). Methods: Adult male Wistar rats were randomly divided into sham operation group and SCI group. The 2 nd sacral spinal cord(S2) of rats in SCI group were transected totally; And then the tail spasticity score of rats were evaluated 2 d, 7 d, 14 d, 30 d and 60 d after operation respectively. Immunofluorescence was used to detect the DRD1 expression in gray matter of sacral and coccygeal spinal cord 60 d after operation. Results: The tail spasticity score of rats in SCI group 2 d, 7 d, 14 d, 30 d and 60 d after operation were respectively 0, 1.10±0.28, 1.32±0.85, 2.50±0.53 and 4.15±0.36.DRD1 expression could be observed in dorsal horn(DH), intermediate zone(IMZ) and ventral horn(VH) in gray matter of sacral and coccygeal spinal cord of rats. The DRD1 expression in DH, IMZ and VH in gray matter of spinal cord of rats in SCI group were significantly lower than rats in sham operation group(P<0.05). Conclusions: Decreased expression of DRD1 in spinal cord after SCI may be associated with development of tail spasticity.
Objective: To study the spasticity of rat tail and the changes of dopamine receptor-1(DRD1) expression in spinal cord after spinal cord injury(SCI). Methods: Adult male Wistar rats were randomly divided into sham operation group and SCI group. The 2 nd sacral spinal cord(S2) of rats in SCI group were transected totally; And then the tail spasticity score of rats were evaluated 2 d, 7 d, 14 d, 30 d and 60 d after operation respectively. Immunofluorescence was used to detect the DRD1 expression in gray matter of sacral and coccygeal spinal cord 60 d after operation. Results: The tail spasticity score of rats in SCI group 2 d, 7 d, 14 d, 30 d and 60 d after operation were respectively 0, 1.10±0.28, 1.32±0.85, 2.50±0.53 and 4.15±0.36.DRD1 expression could be observed in dorsal horn(DH), intermediate zone(IMZ) and ventral horn(VH) in gray matter of sacral and coccygeal spinal cord of rats. The DRD1 expression in DH, IMZ and VH in gray matter of spinal cord of rats in SCI group were significantly lower than rats in sham operation group(P<0.05). Conclusions: Decreased expression of DRD1 in spinal cord after SCI may be associated with development of tail spasticity.
引文
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[14]Zhu H,Clemens S,Sawchuk M,et al.Expression and distribution of all dopamine receptor subtypes(D(1)-D(5))in the mouse lumbar spinal cord:a real-time polymerase chain reaction and non-autoradiographic in situ hybridization study[J].Neuroscience,2007,149(4):885-897.
[15]Kawamoto K,Otsuguro K,Ishizuka M,et al.Inhibitory effects of dopamine on spinal synaptic transmission via dopamine D1-like receptors in neonatal rats[J].Br J Pharmacol,2012,166(2):788-800.
[16]Meneely S,Dinkins ML,Kassai M,et al.Differential Dopamine D1 and D3 Receptor Modulation and Expression in the Spinal Cord of Two Mouse Models of Restless Legs Syndrome[J].Front Behav Neurosci,2018,12:199.
[17]Barraud Q,Obeid I,Aubert I,et al.Neuroanatomical study of the A11 diencephalospinal pathway in the non-human primate[J].PLoS ONE,2010,5(10):e13306.
[18]岳增辉,陈乐乐,朱小姗,等.针刺对脑卒中痉挛大鼠模型大脑皮质DRD1mR NA、DRD2mR NA表达的影响[J].湖南中医药大学学报,2012,32(12):51-54.
[2]Bj?rklund A,Skagerberg G.Evidence for a major spinal cord projection from the diencephalic A11 dopamine cell group in the rat using transmitter-specific fluorescent retrograde tracing[J].Brain Res,1979,177(1):170-175.
[3]万朋,金清华.多巴胺及其受体在中枢神经系统的作用研究进展[J].武汉大学学报(医学版),2017,38(1):169-172.
[4]Feyder M,Bonito-Oliva A,Fisone G.L-DOPA-Induced Dyskinesia and Abnormal Signaling in Striatal Medium Spiny Neurons:Focus on Dopamine D1 Receptor-Mediated Transmission[J].Front Behav Neurosci,2011,5:71.
[5]Ren LQ,Wienecke J,Hultborn H,et al.Production of Dopamine by Aromatic l-Amino Acid Decarboxylase Cells after Spinal Cord Injury[J].J Neurotrauma,2016,33(12):1150-1160.
[6]Wienecke J,Westerdahl AC,Hultborn H,et al.Global gene expression analysis of rodent motor neurons following spinal cord injury associates molecular mechanisms with development of postinjury spasticity[J].J Neurophysiol,2010,103(2):761-778.
[7]Bennett DJ,Gorassini M,Fouad K,et al.Spasticity in rats with sacral spinal cord injury[J].J Neurotrauma,1999,16(1):69-84.
[8]Bennett DJ,Sanelli L,Cooke CL,et al.Spastic long-lasting reflexes in the awake rat after sacral spinal cord injury[J].JNeurophysiol,2004,91(5):2247-2258.
[9]Ren LQ,Wienecke J,Chen M,et al.The time course of serotonin2C receptor expression after spinal transection of rats:an immunohistochemical study[J].Neuroscience,2013,236:31-46.
[10]Nielsen JB,Crone C,Hultborn H.The spinal pathophysiology of spasticity-from a basic science point of view[J].Acta Physiol(Oxf),2007,189(2):171-180.
[11]Zhang YP,Burke DA,Shields LB,et al.Spinal cord contusion based on precise vertebral stabilization and tissue displacement measured by combined assessment to discriminate small functional differences[J].J Neurotrauma,2008,25(10):1227-1240.
[12]Xue F,Wei Y,Chen Y,et al.A rat model for chronic spinal nerve root compression[J].Eur Spine J,2014,23(2):435-446.
[13]Azam B,Wienecke J,Jensen DB,et al.Spinal Cord Hemisection Facilitates Aromatic L-Amino Acid Decarboxylase Cells to Produce Serotonin in the Subchronic but Not the Chronic Phase[J].Neural Plast,2015,2015:549671.
[14]Zhu H,Clemens S,Sawchuk M,et al.Expression and distribution of all dopamine receptor subtypes(D(1)-D(5))in the mouse lumbar spinal cord:a real-time polymerase chain reaction and non-autoradiographic in situ hybridization study[J].Neuroscience,2007,149(4):885-897.
[15]Kawamoto K,Otsuguro K,Ishizuka M,et al.Inhibitory effects of dopamine on spinal synaptic transmission via dopamine D1-like receptors in neonatal rats[J].Br J Pharmacol,2012,166(2):788-800.
[16]Meneely S,Dinkins ML,Kassai M,et al.Differential Dopamine D1 and D3 Receptor Modulation and Expression in the Spinal Cord of Two Mouse Models of Restless Legs Syndrome[J].Front Behav Neurosci,2018,12:199.
[17]Barraud Q,Obeid I,Aubert I,et al.Neuroanatomical study of the A11 diencephalospinal pathway in the non-human primate[J].PLoS ONE,2010,5(10):e13306.
[18]岳增辉,陈乐乐,朱小姗,等.针刺对脑卒中痉挛大鼠模型大脑皮质DRD1mR NA、DRD2mR NA表达的影响[J].湖南中医药大学学报,2012,32(12):51-54.