血小板源性生长因子受体在实验性蛛网膜下腔出血后早期脑损伤中的作用被引量：1

Role of platelet-derived growth factor receptor in early brain injury following subarachnoid hemorrhage

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摘要目的通过研究大鼠蛛网膜下腔出血(subarachnoid hemorrhage,SAH)后脑水肿及细胞凋亡情况,初步探讨血小板源性生长因子受体(platelet-derived growth factor receptor,PDGFR)参与早期脑损伤的可能机制。方法采用随机数字表法将成年雄性SD大鼠分配至假手术组、SAH组、SAH+Imatinib组、SAH+PDGF-BB组。Imatinib为PDGFR拮抗剂,PDGF-BB为其激动剂,每组18只。采用血管内丝线穿刺颈内动脉分叉处的方法,建立SAH模型。SAH+Imatinib组大鼠在建模前1 h,行腹腔注射Imatinib处理;SAH+PDGF-BB组大鼠建模前1 h,行侧脑室注射PDGF-BB处理。处理后24 h,对各组动物的死亡率、神经功能学评分和脑水含量指标进行研究;RT-PCR、Western blot检测海马组织Caspase-3的表达。结果 SAH+PDGF-BB组大鼠死亡率、脑组织含水量最高,神经行为功能学评分最低(P<0.01);SAH+Imatinib组与SAH组比较,大鼠死亡率、脑组织含水量有所下降,神经行为功能学评分有所提高(P<0.01);与其他组比较,SAH+PDGF-BB组大鼠海马组织Caspase-3 mRNA表达最高(P<0.01),SAH+Imatinib组与SAH组比较,海马组织Caspase-3mRNA表达有所下降(P<0.01);Western blot检测趋势与RT-PCR检测结果一致。结论 PDGFR参与SAH后早期脑损害,其拮抗剂Imatinib能在一定程度上减轻早期脑损伤。 Objective To observe cephaledema and cell apoptosis in rats following subarachnoid hemorrhage （ SAH）, and to explore the mechanism of platelet-derived growth factor receptor （PDGFR） invol- ving in the development of early brain injury. Methods Adult male SD rats were randomly divided into 4 groups including a sham operation group, a SAH group, a SAH ＋ imatinib group, and a SAH ＋ PDGF-BB group （ n = 18 ）. SAH mouse models were established by using intravascular silk puncture of the internal carotid artery crotch. The rats of the SAH ＋ imatinib group were given an intraperitoneal injection of imatinib at 1 h before modeling, while those of the SAH ＋ PDGF-BB group were given an intracerebroventricular injection of PDGF-BB at 1 h before modeling. After treatment for 24 h, the mortality, water content in brain and neurological function score were determined. Caspase-3 expression in hippocampus was detected by RT-PCR and Western blotting. Results The mortality, brain water content and caspase-3 expression level were the highest in the SAH ＋ PDGF-BB group, but the neurological function score was the lowest （P 〈 0.01 ）. The parameters were reduced when SAH rats were injected with imatinib （P 〈 0.01 ）. Conclusion PDGFR may participate in the pathogene- sis of early brain injury following SAH, and its antagonist imatinib can reduce brain iniurv to a certain degree.

作者张光伟贺学农周昌龙夏小辉孙晓川谢延风

机构地区重庆医科大学附属永川医院神经外科重庆医科大学附属第一医院神经外科

出处《第三军医大学学报》 CAS CSCD 北大核心 2013年第13期1398-1401,共4页 Journal of Third Military Medical University

关键词蛛网膜下腔出血早期脑损伤血小板源性生长因子受体凋亡脑水肿 aneurysmal subarachnoid hemorrhage early brain injury platelet-derived growth factorreceptor apoptosis cephaledema

分类号 R341 [医药卫生—基础医学]

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参考文献14

1Kusaka G, Ishikawa M, Nanda A, et al. Signaling pathways for early brain injury after suba.,'achnoid hemorrhage [ J ]. J Cereb Blood Flow Metab, 2004, 24(8) : 916 -925.
2Cahi , Calvert ] W, Zhang ] It. Mechanisms of early brain injury af- ter subarachnoid hemorrhage[ J]. J Cereb Blood Flow Metab, 2006, 26(11) : 1341 -1353.
3Maeda Y, Hirano K, Hirano M, et al. Enhanced contractile response of the basilar artery to platelet-derlved growth factor in subarachnoid hemorrhage[J]. Stroke, 2009, 40(2) : 591 -596.
4Hughes A D, Clunn G F, Refson J, et al. Platelet-derived growth fac- tor (PDGF) : actions and mechanisms in vascular smooth muscle[ J ].Gen Pharmacol, 1996, 27(7): 1079-1089.
5Bogoyeviteh MA, Kobe B. Uses for JNK: the many and varied sub- strates of the c-Jun N-terminal kinases [ J]. Microbiol Mol Biol Rev, 2006, 70(4) : 1061 - 1095.
6Bederson J B, Germano I M, Guarino L. Cortical blood flow and cere- bral perfusion pressure in a new noncraniotomy model of subarachnoid hemorrhage in the rat [J]. Stroke, 1995, 26(6) : 1086 -1092.
7Sibon I, Menegon P, Rouanet F, et al. MRI of acute brainstem ischae- mia: cytotoxic versus vasogenic oedema? [ J]. Eur J Neurol, 2004, 11 (7) : 497 -498.
8陈佳琳,姚声涛,郭宗铎.TNF-α在实验性蛛网膜下腔出血后早期脑损伤中的作用[J].第三军医大学学报,2011,33(15):1620-1622. 被引量：5
9Zhou M L, Shi J X, Hang C H, et al. Potential contribution of nuclear factor-kappaB to cerebral vasospasm after experimental subaraehnoid hemorrhage in rabbits[Jl. J Cereb Blood Flow Metab, 2007, 27(9) : 1583 - 1592.
10Yatsushi~e H, Ostrowski R P, Tsubokawa T. et al. Role of c-Jun N-terminal kinase in early brain injury after subarachnoid hemorrhage [ J]. J Neurosci Res, 2007, 85 (7) : 1436 - 1448.

二级参考文献14

1Broderick J P, Brott T G, Duldner J E, et al. Initial and reecurrent bleeding are the major causes of death following subaracbnoid hemorrhage[J]. Stroke, 1994, 25(7) :1342-1347.
2Simard J M, Geng Z, Woo S K, et al. Glibenelamide reduces inflammation, vasogenic edema, and caspase-3 activation after subaraclmoid hemorrhage[J]. J Cereb Blood Flow Metab, 2009, 29(2): 317 - 330.
3Reyes R, Guo M, Swann K, et al. Role of tumor necrosis factor-alpha and matrix metalloproteinase-9 in blood-brain barrier disruption after peripheral thermal injury in rats [ J ]. J Neurosurg, 2009, 110 ( 6 ) : 1218 - 1226.
4Lin C C, Tseng H W, Hsieh H L, et al. Tumor necrosis tactnr-alpha induces MMP-9 expression via p42/p44 MAPK, JNK, and nuclfear fautor-kappaB in A549 cells [ J]. Toxicol Appl Pharmacol, 2008, 229 (3) : 386 -398.
5Yamaguchi M, Zhou C, Nanda A, et al. Ras protein contributes to cerebral vasospasm in a canine doublehemorrhage model[ J ]. Stroke 2004, 35(7) :1750 - 1755.
6Kusaka G, lshikawa M, Nanda A, et al. Signaling pathways for early brain injmy aftcer subarachnoid hemorrhage [J ]. J Cereh Blood Florw Metab, 2004, 24 ( 8 ) : 916 - 925.
7Fontanella M, Rainero I, Gallonc S, et al. Tumor necrosis ihctor-alpha gene and cerebral anem?sms[ J]. Neurosurgery, 2007, 60(4) : 668 - 672.
8Fassbender K, Hodapp B, Rossol S, et al. Inflammatory cytokincs in subarachnoid haemorrhage: association with abnormal blood flow vefocities in basal cerebral arteries[ J]. J Neurol Neurosurg Psychiat, 2001, 70(4) : 534 -537.
9Pmnell G F, Svendgaard N A, Alkass K, et al. Inflammation in the brain Lifter experimental sullaraehnoid hemorrhage[J]. Neurosurgery, 2005, 56(5) : /082 - 1092.
10Wu J, Yang S, Xi G, et al. Minocycline reduces intracerebral hemorrhage-induced brain injury[J ]. Neurol lies, 2009, 31 (2) : 183 - 188.