雷帕霉素靶蛋白病中Caspase-3、Caspase-9、Bax的表达及其意义
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摘要
目的检测Caspase-3、Caspase-9和Bax在雷帕霉素靶蛋白病致痫病灶中的表达,初步探讨凋亡在该疾病中的意义。方法选用38例手术切除的致痫病灶标本,包括9例局灶性皮质发育不良Ⅱb型(focal cortical dysplasiaⅡb,FCDⅡb)、15例结节性硬化复合征(tuberous sclerosis complex,TSC)和14例节细胞胶质瘤(ganglioglioma,GG),采用免疫组化Max Vision两步法检测Caspase-3、Caspase-9和Bax的表达,计数染色阳性细胞数并进行比较分析,与临床资料进行相关性分析。结果 Caspase-3阳性细胞数在GG组显著大于TSC组和FCDⅡb组(P<0.05);Caspase-9阳性细胞数在FCDⅡb组显著大于TSC和GG组(P<0.05)。FCDⅡb组中Bax阳性细胞数与病程有显著相关性(P<0.05);GG组中Caspase-3阳性细胞数与发病年龄有显著相关性(P<0.05)。结论在雷帕霉素靶蛋白病(FCDⅡb、TSC、GG)致痫病灶中存在凋亡相关蛋白的表达,凋亡在病变形成中发挥作用,但其具体机制尚不明确。
Purpose To study the expression of apoptosis-related proteins( Caspase-3,Caspase-9 and Bax) in epileptic focus with TOR opathies and to discuss the significance of apoptosis in the diseases. Methods The brain tissue of 38 cases who underwent resection of epileptic focus,including 9 cases of focal cortical dysplasia Ⅱb( FCDⅡb),15 cases of tuberous sclerosis complex( TSC) and14 cases of ganglioglioma( GG) were studied for expression of Caspase-3,Caspase-9 and Bax by immunohistochemistry of Max Vision two-step. The positive cells were compared between groups and the possible correlation with different clinical variables were analysed.Results Number of Caspase-3 positive cells in GG was significantly greater than the TSC and FCD IIb( P < 0. 05). Number of Caspase-9 positive cells in FCD IIb was significantly greater than the TSC and GG( P < 0. 05). Positive cells of Bax in FCD IIb positively correlated with duration of epilepsy( P < 0. 05). Positive cells of Caspase-3 in GG positively correlated with onset age( P <0. 05). Conclusion The epileptic focus of TOR opathies( FCDⅡb,TSC and GG) show the expression of apoptosis-related proteins.Apoptosis may play a role in the formation of lesions,but the exact mechanism is unclear.
Purpose To study the expression of apoptosis-related proteins( Caspase-3,Caspase-9 and Bax) in epileptic focus with TOR opathies and to discuss the significance of apoptosis in the diseases. Methods The brain tissue of 38 cases who underwent resection of epileptic focus,including 9 cases of focal cortical dysplasia Ⅱb( FCDⅡb),15 cases of tuberous sclerosis complex( TSC) and14 cases of ganglioglioma( GG) were studied for expression of Caspase-3,Caspase-9 and Bax by immunohistochemistry of Max Vision two-step. The positive cells were compared between groups and the possible correlation with different clinical variables were analysed.Results Number of Caspase-3 positive cells in GG was significantly greater than the TSC and FCD IIb( P < 0. 05). Number of Caspase-9 positive cells in FCD IIb was significantly greater than the TSC and GG( P < 0. 05). Positive cells of Bax in FCD IIb positively correlated with duration of epilepsy( P < 0. 05). Positive cells of Caspase-3 in GG positively correlated with onset age( P <0. 05). Conclusion The epileptic focus of TOR opathies( FCDⅡb,TSC and GG) show the expression of apoptosis-related proteins.Apoptosis may play a role in the formation of lesions,but the exact mechanism is unclear.
引文
[1]Meng X F,Yu J T,Song J H,et al.Role of the m TOR signaling pathway inepilepsy[J].J Neurol Sci,2013,332(1/2):4-15.
[2]Sarnat H B,Flores-Sarnat L.Infantile tauopathies:hemimegalencephaly,tuberous sclerosis complex,focal cortical dysplasia 2,ganglioglioma[J].Brain Dev,2015,37(6):553-62.
[3]Liu J,Reeves C,Michalak Z,et al.Evidence for m TOR pathway activation in a spectrum of epilepsy-associated pathologies[J].Acta Neuropathol Commun,2014,2:71.
[4]Blümcke I,Thom M,Aronica E,et al.The clinicopathologic spectrum of focal cortical dysplasias:a consensus classification proposed by an ad hoc task force of the ILAE diagnostic methods commission[J].Epilepsia,2011,52:158-74.
[5]Northrup H,Krueger D A.International Tuberous sclerosis complex consensus group.Tuberous sclerosis complex diagnostic criteria update:recommendations of the 2012 Iinternational Tuberous sclerosis complex consensus conference[J].Pediatr Neurol,2013,49(4):243-54.
[6]Louis D N,Ohgaki H,Wiestler O D,et al.WHO classification of tumours of the central nervous system[M].Lyon:IARC Press,2007:22-113.
[7]Lin L,Baehrecke E H.Autophagy,cell death,and cancer[J].Mol Cell Oncol,2015,2(3):e985913.
[8]陈诗赟,朴月善,付永娟,等.自噬相关蛋白在皮质发育畸形病变中的表达[J].中华病理学杂志,2015,44(5):305-9.
[9]Iyer A,Prabowo A,Anink J,et al.Cell injury and premature neurodegenerationin focal malformations of cortical development[J].Brain Pathol,2014,24:1-17.
[10]Boer K,Crino P B,Gorter J A,et al.Gene expression analysis of tuberous sclerosis complex cortical tubers reveals increased expression of adhesion and inflammatory factors[J].Brain Pathol,2010,20(4):704-19.
[11]Barkovich A J,Guerrini R,Kuzniecky R I,et al.A developmental and genetic classification for malformations of cortical development:update 2012[J].Brain,2012,135(Pt 5):1348-69.
[12]Prabowo A S,Iyer A M,Veersema T J,et al.Expression of neurodegenerative disease-related proteins and Caspase-3 in glioneuronal tumours[J].Neuropathol Appl Neurobiol,2015,41(2):e1-15.
[13]Wang X.The expanding role of mitochondria in apoptosis[J].Genes Dev,2001,15(22):2922-33.
[14]Ma Y,Yang H Z,Dong B J,et al.Biphasic regulation of autophagy bymi R-96 inprostatecancercells under hypoxia[J].Oncotarget,2014,5:9169-82.
[15]D’Amelio M,Cavallucci V,Cecconi F.Neuronal Caspase-3 signaling:not only cell death[J].Cell Death Differ,2010,17:1104-14.
[16]Mc Ilwain D R,Berger T,Mak T W.Caspase functions in cell death and disease[J].Cold Spring Harb Perspect Biol,2013,5(4):a008656.
[2]Sarnat H B,Flores-Sarnat L.Infantile tauopathies:hemimegalencephaly,tuberous sclerosis complex,focal cortical dysplasia 2,ganglioglioma[J].Brain Dev,2015,37(6):553-62.
[3]Liu J,Reeves C,Michalak Z,et al.Evidence for m TOR pathway activation in a spectrum of epilepsy-associated pathologies[J].Acta Neuropathol Commun,2014,2:71.
[4]Blümcke I,Thom M,Aronica E,et al.The clinicopathologic spectrum of focal cortical dysplasias:a consensus classification proposed by an ad hoc task force of the ILAE diagnostic methods commission[J].Epilepsia,2011,52:158-74.
[5]Northrup H,Krueger D A.International Tuberous sclerosis complex consensus group.Tuberous sclerosis complex diagnostic criteria update:recommendations of the 2012 Iinternational Tuberous sclerosis complex consensus conference[J].Pediatr Neurol,2013,49(4):243-54.
[6]Louis D N,Ohgaki H,Wiestler O D,et al.WHO classification of tumours of the central nervous system[M].Lyon:IARC Press,2007:22-113.
[7]Lin L,Baehrecke E H.Autophagy,cell death,and cancer[J].Mol Cell Oncol,2015,2(3):e985913.
[8]陈诗赟,朴月善,付永娟,等.自噬相关蛋白在皮质发育畸形病变中的表达[J].中华病理学杂志,2015,44(5):305-9.
[9]Iyer A,Prabowo A,Anink J,et al.Cell injury and premature neurodegenerationin focal malformations of cortical development[J].Brain Pathol,2014,24:1-17.
[10]Boer K,Crino P B,Gorter J A,et al.Gene expression analysis of tuberous sclerosis complex cortical tubers reveals increased expression of adhesion and inflammatory factors[J].Brain Pathol,2010,20(4):704-19.
[11]Barkovich A J,Guerrini R,Kuzniecky R I,et al.A developmental and genetic classification for malformations of cortical development:update 2012[J].Brain,2012,135(Pt 5):1348-69.
[12]Prabowo A S,Iyer A M,Veersema T J,et al.Expression of neurodegenerative disease-related proteins and Caspase-3 in glioneuronal tumours[J].Neuropathol Appl Neurobiol,2015,41(2):e1-15.
[13]Wang X.The expanding role of mitochondria in apoptosis[J].Genes Dev,2001,15(22):2922-33.
[14]Ma Y,Yang H Z,Dong B J,et al.Biphasic regulation of autophagy bymi R-96 inprostatecancercells under hypoxia[J].Oncotarget,2014,5:9169-82.
[15]D’Amelio M,Cavallucci V,Cecconi F.Neuronal Caspase-3 signaling:not only cell death[J].Cell Death Differ,2010,17:1104-14.
[16]Mc Ilwain D R,Berger T,Mak T W.Caspase functions in cell death and disease[J].Cold Spring Harb Perspect Biol,2013,5(4):a008656.