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- 2015
IP3R1在弥漫性轴索损伤后早期的表达及其意义
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Abstract:
摘要:目的 通过观察大鼠弥漫性轴索损伤(diffuse axonal injury, DAI)后I型1,4,5-三磷酸肌醇受体(inositol 1,4,5-trisphosphate receptor type I, IP3R1)表达随时间的变化,探讨其作用,为DAI后轴索的继发性损伤及断裂提供研究基础。方法 25只健康雄性成年SD大鼠,随机分为对照组和实验组(DAI组),采用Golgi镀银染色及SP免疫组织化学染色,观察其在不同时间(3~72h)的脑干组织病理变化及IP3R1的表达情况。结果 Golgi镀银染色证明大鼠DAI模型成功;免疫组织化学染色显示,对照组大鼠脑干中IP3R1有弱阳性表达,实验组阳性细胞较对照组明显增高,在DAI损伤后,大鼠脑干组织IP3R1表达3h时就开始升高,至24h高峰后开始下降,72h下降至低水平。结论 IP3R1可能在DAI后轴索的继发性损伤及断裂中起重要作用。
ABSTRACT: Objective To detect the dynamic expression level of inositol 1, 4, 5-trisphosphate receptor type I (IP3R1) in rat brain stem after diffuse axonal injury (DAI) by immunohistochemistry so as to explore its potential contribution to the secondary injury after DAI. Methods Twenty-five male adult Sprague-Dawley rats were divided into the injury group (n=25) and the control group (n=5). Before immunohistochemistry detection, Golgi silver staining was performed to ensure all rats in DAI group met the criteria of DAI. Then the level of IP3R1 expression was detected by immunohistochemistry at 3h, 12h, 24h and 72h after DAI, respectively. Results In the DAI group, a subset of axons exhibited bead-like structure, axonal retraction balls and swollen axons, and axonal axotomy was observed with Golgi silver staining. Immunohistochemical results showed mild expression of IP3R1 in the rat brain stem in the control group. After DAI the level of IP3R1 expression increased significantly. It began to increase at 3h after injury (PI), peaked at 24h PI, and then gradually decreased. At 72h PI, the expression in DAI group did not significantly differ from that in the control group. Conclusion Enhanced expression of IP3R1 may participate in the calcium overload and neuronal secondary injury in the early stage after DAI
[1] | 宋锦宁,刘守勋,戈治理,等. 脑弥漫性轴索损伤的特点及临床诊断[J]. 中国神经精神疾病杂志, 1997, 23(3): 141-144. |
[2] | RUIZ A, MATUTE C, ALBERDI E. Endoplasmic reticulum Ca<sup>2+</sup> release through ryanodine and IP3 receptors contributes to neuronal excitotoxicity[J]. Cell Calcium, 2009, 46(4): 273-281. |
[3] | PEREIRA GJ, HIRATA H, FIMIA GM, et al. Nicotinic acid adenine dinucleotide phosphate (NAADP) regulates autophagy in cultured astrocytes[J]. J Biol Chem, 2011, 286(32):27875-27881. |
[4] | 刘晓斌,宋锦宁,陈景宇,等. 脑弥漫性轴索损伤实验装置的研制及动物模型的建立[J]. 西安交通大学学报:医学版, 2008, 29(5):595-598. |
[5] | SONG J, LIU X, CHEN J, et al. Dynamic changes in cerebral microcirculation and hypoxia in the early stages of diffuse axonal injury[J]. Neural Regeneration Res, 2011, 6(20):1530-1536. |
[6] | IONESCU L, WHITE C, CHEUNG KH, et al. Mode switching is the major mechanism of ligand regulation of InsP3 receptor calcium releasechannels[J]. Gen Physiol, 2007, 130(6):631-645. |
[7] | LINGOR P, KOCH JC, T?ZNGES L, et al. Axonal degeneration as a therapeutic target in the CNS[J]. Cell Tissue Res, 2012, 349(1):289-311. |
[8] | KRAWCZYK-RUSIECKA K, LEWINSKI A. Cyclooxygenase-2 expression and its association with thyroid lesions[J]. Arch Med Sci, 2010, 6(5):653-657. |
[9] | THEILE JW, JARECKI BW, PIEKARZ AD, et al. Nav1.7 mutations associated with paroxysmal extreme pain disorder, but not erythromelalgia, enhance Navβ4 peptide-mediated resurgent sodium currents[J]. J Physiol, 2011, 589:597-608. |
[10] | NEHRT A, RODGERS R, SHAPIRO S, et al. The critical role of voltage-dependent calcium channel in axonal repair following mechanical trauma[J]. Neuroscience, 2007, 146(4):1504-1512. |