Effects of huwentoxin on tumor necrosis factor apoptotic pathway in the hippocampus of a rat model of cerebral ischemia

doi:10.3969/j.issn.2095-4344.2014.36.013

Abstract

Abstract:

BACKGROUND: Ion channel analytical technique has verified that huwentoxin is an N-type Ca²⁺ channel blocker affecting on presynaptic membrane.
OBJECTIVE: To observe the effects of N-type Ca2+ channel blocker huwentoxin on expressions of tumor necrosis factor α, tumor necrosis factor receptor I, tumor necrosis factor receptor-related death domain, Fas-related death domain protein and Caspase 8 in the hippocampi of rat models of global cerebral ischemia reperfusion injury.
METHODS: Rat models of global cerebral ischemia and subarachnoid catheter were established using Pulsinelli 4-vessel occlusion and then received infusion of huwentoxin or normal saline via a PE10 tube. Morphological changes in the mitochondria and ultrastructure of pyramidal neurons in the hippocampal CA1 region of rats with global cerebral ischemia reperfusion injury were observed using electron microscope. The expressions of tumor necrosis factor α, tumor necrosis factor receptor I, tumor necrosis factor receptor-related death domain, Fas-related death domain protein and Caspase 8 were measured using RT-PCR.
RESULTS AND CONCLUSION: Huwentoxin could maintain the basic morphology of mitochondria of rats with global cerebral ischemia reperfusion injury and decrease the expressions of tumor necrosis factor α, tumor necrosis factor receptor I, tumor necrosis factor receptor-related death domain, Fas-related death domain protein and Caspase 8 mRNA. Results suggested that huwentoxin as a novel N-type Ca²⁺ channel blocker could block extracellular Ca²⁺ influx, reduce intracellular Ca²⁺ concentration, diminish a series of pathological lesion induced by intracellular Ca²⁺ overload, protect nerve cells, and lessen the injury to nerve cells of hippocampus after ischemia and hypoxia.

中国组织工程研究杂志出版内容重点：肾移植；肝移植；移植；心脏移植；组织移植；皮肤移植；皮瓣移植；血管移植；器官移植；组织工程

全文链接：

Key words: reperfusion injury, tumor necrosis factor-alpha, receptor, tumor necrosis factor, type I, caspase 8

CLC Number:

R318

Wang Yi-rong, Mao Hai-feng, Chen Jia-qin . Effects of huwentoxin on tumor necrosis factor apoptotic pathway in the hippocampus of a rat model of cerebral ischemia[J]. Chinese Journal of Tissue Engineering Research, 2014, 18(36): 5813-5818.

Figures/Tables 3

References

[1] Lipton P.Ischemic Cell Death in Brain Neurons. Physiol Rev. 1999;79(4):1431-568.
[2] 王薇,赵冬,刘静,等.中国35~64岁人群血压水平与10年心血管病发病危险的前瞻性研究[J].中华内科杂志,2004,43(10): 730-734.
[3] Takehashi T, Moniyama A. Different type of calcium channels mediate central synaptic transmission. Nature (London).1993; 366:156-158.
[4] Peng K, Chen XD, Liang SP，et al. The effect of Huwentoxin-I on Ca2+ channels in differentiated NG108-15 cells, a patch-clamp study. Toxicon. 2001;39(4):491-498.
[5] Jiaqin C, Yongquen Z, Jie D, et al. Antinociceptive effects of intrathecally administered huwentoxin-I, a selective N-type calcium channel blocker, in the formalin test in conscious rats. Toxicon.2005;45:15-20.
[6] Jiaqin C, Weihua C, Meichun D, et al. Huwentoxin-I: antinociceptive effects and its comparison with -conotoxin-MVIIA on acute visceral pain in rats. Chinese Journal of Biochemistry and Molecular Biology. 2005;21(1): 24-29.
[7] Valentino K, Newcomb R，Gadbois T, et al. A selective N-type calcium channel antagonist protects against neuronal loss after global cerebral ischemia. neurobiology.1993;90: 7894-7897.
[8] Smith MT, Cabot PT, Ross FB, et al. The novel N-type calcium channel blocker, AM336, produces potent dose-dependent antinociception after intrathecal dosing in rats and inhibits substance P release in rat spinal cord slices. Pain.2002; 96:119-127.
[9] Yaksh TL, Rudy A. Chronic catheterization of the spinal subarachnoid space. Physiol Behav.1976;17:175-185.
[10] Pulsinelli WA, Brierley JB. A new model of bilateral hemispheric ischemic in the unanesthetized rat. Stroke. 1979;10(3):267-272.
[11] Frederick C, Hui L, Alastair M, et al. Continuing Postischemic Neuronal Death in CA1 Influence of Ischemia Duration and Cytoprotective Doses of NBQX and SNX-111 in Rats. Stroke. 1999;30:662-668.
[12] 袁春华.两种虎纹捕鸟蛛毒素的结构与功能研究[J].长沙:湖南师范大学:生物化学与分子生物学,2003.
[13] 毛海峰,陈嘉勤,周鸿燕,等.SD大鼠全全脑缺血结合蛛网膜下腔置管模型的构建[J].湖南师范大学学报医学版,2005,2(1):46-49.
[14] 毛海峰,陈嘉勤,周鸿燕,等.HWTX-I对全脑缺血大鼠脑组织自由基及海马神经元损伤的保护作用研究[J].北京体育大学学报, 2007,30(3):351-353.
[15] 吴坤,赵艳,于卫平.细胞凋亡的研究进展[J].国外医学:遗传学分册,2001,24(3):134-138.
[16] Liu Z, Jiao QF, You C, et al. Effect of hyperbaric oxygen on cytochrome C, Bcl-2 and bax expression after experimental traumatic brain injury in rats.Chin J Traumatol.2006;9(3): 168-174.
[17] Fall CP, Bennett JP Jr. Visualization of cyclosporin A and Ca2+-sensitive cyclical mitochondrial depolarizations in cell culture. Biochim Biophys Acta. 1999;1410(1):77-84.
[18] Chan PH. Mitochondria and neuronal death/survival signaling pathways in cerebral ischemia. Neurochem Res.2004;29(11): 1943-1949.
[19] Yan N, Shi Y. Mechanisms of apoptosis through structural biology. Annu Rev Cell Dev Biol.2005;21:35-56.
[20] 吴刚,薛荣亮.死亡受体介导的信号转导与脑缺血再灌注损伤[J].国外医学:麻醉学与复苏分册,2004,25(1):11-15.
[21] Berti R, Williams AJ, Moffett JR, et al. Quantitative real-time RT-PCR analysis of inflammatory gene expression associated with ischemia-reperfusion brain injury. J Cereb Blood Flow Metab. 2002;22(9);1068-1079.
[22] Wang CX. Shuaib A. Involvement of inflammatory cytokines in central nervous system injury. Prog Neurobiol.2002,67(2): 161-172.
[23] Malink T, Bailey F, Zhang IG, et al. Nitric oxide measured by a porˉphyrinic microsensor in rat brain after transient middle flow. Metab.1993;13:335-338.
[24] Rothstein JD, Bristol LA, Hosler B, et al. Chronic inhibition of superoxide dismutase produces apoptosis: a role for reactive oxygen species in program-medneuronal death. Neuron.1995; 14:303-315.