脑梗死模型大鼠缺血脑组织中胰岛素样生长因子结合蛋白3表达水平及其与血管新生的关系

doi:10.13481/j.1671-587x.20200415

Abstract

Abstract: Objective: To investigate the expression level of insulin-like growth factor binding protein-3(IGFBP-3) in ischemic brain tissue of the rats with cerebral infarction and its relationship with angiogenesis,and to elucidate the role of IGFBP-3 in angiogenesis of cerebral infarction. Methods: The SD rats were randomly divided into control group and model group,and the rats in model group were divided into three subgroups of model 1 d group, model 3 d group and model 7 d group, with 30 rats in each group.The rat model of middle cerebral artery occlusion ischemia was established by suture method.Neurobehavioral score method was used to assess the neural behavior of the rats.Cerebral infarctions were observed by 2,3,5-triphenyltetrazolium chloride (TTC) staining.The pathomorphology of brain tissue of the rats was observed by HE staining.Immunohistochemical staining was used to measure the expression levels of IGFBP-3 and vascular endothelial growth factor (VEGF) proteins in brain tissue of the rats.Reverse transcription-polymerase chain reaction (RT-PCR) was used to measure the expression levels of IGFBP-3 and VEGF mRNA in brain tissue of the rats.Immunofluorescence staining was used to measure the microvessel density in the ischemic penumbra of the brain tissue of the rats. Results: There were no neurological deficits and cerebral infarction of the rats in control group.In model group,the neurobehavioral score of the rats was (1.86±0.73) scores and the volume of cerebral infarction was (28.34±3.57)%.The HE staining results showed that the brain tissue of the rats in control group was normal;in model 1 d group,edema occurred in the brain tissue of the rats; in model 3 d group,edema and necrosis of brain tissue of the rats were obvious; in model 7 d group, edema and necrosis of brain tissue were alleviated.Compared with control group, the expression levels of IGFBP-3 and VEGF proteins and mRNA in brain tissue of the rats in various model groups and the microvessel densities in ischemic penumbra were increased (P<0.01);the above indexes in brain tissue of the rats in model 3 d group were the highest;the expression levels of IGFBP-3 and VEGF proteins and mRNA in brain tissue of the rats in model 7 d group and the microvessel density in ischemic penumbra were decreased.There were positive correlation between the expression levels of IGFBP-3 mRNA and the VEGF mRNA and microvessel density in brain tissue of the rats (r=0.563,P<0.05;r=0.612,P<0.05). Conclusion: The expression level of IGFBP-3 in ischemic brain tissue of the rats with cerebral infarction is increased, which may promote angiogenesis after cerebral infarction.

Key words: cerebral infarction, insulin-like growth factor binding protein-3, vascular endothelial growth factor, angiogenesis

CLC Number:

R743.3

BU Yi, ZHANG Shuo, QIAN Xudong, WANG Hongmei, DOU Zhijie. Expression of insulin-like growth factor binding protein-3 in ischemic brain tissue of cerebral infarction model rats and its relationship with angiogenesis[J].Journal of Jilin University(Medicine Edition), 2020, 46(04): 759-764.

References

[1] LIANG Y, CHEN J, ZHENG X,et al.Ultrasound-mediated kallidinogenase-loaded microbubble targeted therapy for acute cerebral infarction[J].J Stroke Cerebrovasc Dis,2018,27(3):686-696.
[2] KUSHLINSKⅡ N E, GERSHTEIN E S, NIKOLAEV A A, et al. Insulin-like growth factors (IGF), IGF-binding proteins (IGFBP), and vascular endothelial growth factor (VEGF) in blood serum of patients with colorectal cancer[J]. Bull Exp Biol Med, 2014, 156(5):684-688.
[3] BAKOPOULOU A, KRITIS A, ANDREADIS D, et al. Angiogenic potential and secretome of human apical papilla mesenchymal stem cells in various stress microenvironments[J]. Stem Cells Dev, 2015, 24(21):2496-2512.
[4] LONGA E Z, WEINSTEIN P, CARLSON S, et al. Reversible middle cerebral artery occlusion without craniectomy in rats[J]. Stroke, 1989, 20(1):84-91.
[5] WANG W, WU B Q, CHEN G B,et al.Meta-analysis of the association of IGFBP3 and IGF1 polymorphisms with susceptibility to colorectal cancer[J].Neoplasma, 2018,65(6):855-864.
[6] DENG M Y, LUO K Y, HOU T Y, et al. IGFBP3 deposited in the human umbilical cord mesenchymal stem cell-secreted extracellular matrix promotes bone formation[J]. J Cell Physiol, 2018, 233(8):5792-5804.
[7] CHAN Y X, ALFONSO H, PAUL CHUBB S A,et al.Higher IGFBP3 is associated with increased incidence of colorectal cancer in older men independently of IGF1[J].Clin Endocrinol (Oxf), 2018,88(2):333-340.
[8] 张冬梅,张文芳,鲁建华,等.大鼠视网膜缺血再灌注后IGF-1及IGFBP-3的表达和意义[J].国际眼科杂志,2012,12(3):413-415.
[9] PLEŞERU A M, MIHAILĂ R G. The role of thrombin in central nervous system activity and stroke[J]. Clujul Med, 2018, 91(4):368-371.
[10] WU H, GUO P, LI X,et al.Hydroxybutyrate promotes the recovery from cerebral infarction by activating Amp-activated protein kinase signaling[J].Exp Ther Med,2018,16(2):1195-1202.
[11] LEE H J, LEE J S, HWANG S J,et al.Insulin-like growth factor binding protein-3 inhibits cell adhesion via suppression of integrin β4 expression[J]. Oncotarget, 2015, 6(17):15150-15163.
[12] MIWA T, KOKURYO T, YOKOYAMA Y, et al. Therapeutic potential of targeting protein for Xklp2 silencing for pancreatic cancer[J]. Cancer Med, 2015, 4(7):1091-1100.
[13] SUZUKI S, MORIMOTO S, FUJISHIRO M, et al. Inhibition of the insulin-like growth factor system is a potential therapy for rheumatoid arthritis[J]. Autoimmunity, 2015, 48(4):251-258.
[14] ANGUIANO-HERNANDEZ Y M, CONTRERAS-MENDEZ L, DE LOS ANGELES HERNANDEZ-CUETO M, et al. Modification of HIF-1α, NF-κB, IGFBP-3, VEGF and adiponectin in diabetic foot ulcers treated with hyperbaric oxygen[J]. Undersea Hyperb Med, 2019, 46(1):35-44.
[15] HEGDE P S, WALLIN J J, MANCAO C. Predictive markers of anti-VEGF and emerging role of angiogenesis inhibitors as immunotherapeutics[J]. Semin Cancer Biol, 2018, 52(Pt 2):117-124.
[16] KIM T K, PARK C S, JANG J, et al. Inhibition of VEGF-dependent angiogenesis and tumor angiogenesis by an optimized antibody targeting CLEC14a[J]. Mol Oncol, 2018, 12(3):356-372.
[17] MELINCOVICI C S, BOŞCA A B, ŞUŞMAN S,et al.Vascular endothelial growth factor (VEGF)-key factor in normal and pathological angiogenesis[J].Rom J Morphol Embryol,2018,59(2):455-467.
[18] HU W H, WANG H Y, KONG X P,et al.Polydatin suppresses VEGF-induced angiogenesis through binding with VEGF and inhibiting its receptor signaling[J].FASEB J,2019,33(1):532-544.
[19] JIANG Y D, ZHANG Q H, STEINLE J J. Beta-adrenergic receptor agonist decreases VEGF levels through altered eNOS and PKC signaling in diabetic retina[J]. Growth Factors, 2015, 33(3):192-199.
[20] 戚红霞, 李晓虹, 胡海强. 血清IGF-1、IGFBP-3、VEGF及多项白介素在结直肠癌转移监测中的意义[J]. 海南医学院学报, 2013, 19(2):176-179.
[21] KARLIKOVA M, TOPOLCAN O, NARSANSKA A, et al. Circulating growth and angiogenic factors and lymph node status in early-stage breast cancer-a pilot study[J]. Anticancer Res, 2016, 36(8):4209-4214.
[22] 芦小单,方艳秋,纪艳,等.可逆抑制血管内皮生长因子(VEGF)表达转基因小鼠子宫基因转录谱分析[J].生殖与避孕,2015,35(7):446-451.

Expression of insulin-like growth factor binding protein-3 in ischemic brain tissue of cerebral infarction model rats and its relationship with angiogenesis

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