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中华老年骨科与康复电子杂志

中华老年骨科与康复电子杂志 ›› 2020, Vol. 06 ›› Issue (06) : 327 -333. doi: 10.3877/cma.j.issn.2096-0263.2020.06.003

所属专题： 文献；

骨与创伤

重型创伤性脑损伤合并骨折患者血清CGRP的水平及与预后的关系
程亮1, 朱良宇2, 何涛3,†()   
  1. 1. 065000　廊坊市人民医院神经外科
    2. 050017　石家庄，河北医科大学公共卫生学院
    3. 065000　廊坊市人民医院神经内科
  • 收稿日期:2020-08-27 出版日期:2020-12-05
  • 通信作者: 何涛
  • 基金资助:
    国家自然科学基金(81400322)

Levels of serum CGRP of patients with severe traumatic brain injury combined with fracture and its relationship with prognosis

Liang Cheng1, LiangYu Zhu2, Tao He3,†()   

  1. 1. Department of Neurosurgery, Langfang people's Hospital, Langfang 065000, China
    2. School of Public Health, Hebei Medical University, Shijiazhuang 050017, China
    3. Department of Neurology, Langfang people's Hospital, Langfang 065000, China
  • Received:2020-08-27 Published:2020-12-05
  • Corresponding author: Tao He
  • About author:
    Corresponding author: He Tao, Email:
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引用本文：

程亮, 朱良宇, 何涛. 重型创伤性脑损伤合并骨折患者血清CGRP的水平及与预后的关系[J]. 中华老年骨科与康复电子杂志, 2020, 06(06): 327-333.

Liang Cheng, LiangYu Zhu, Tao He. Levels of serum CGRP of patients with severe traumatic brain injury combined with fracture and its relationship with prognosis[J]. Chinese Journal of Geriatric Orthopaedics and Rehabilitation(Electronic Edition), 2020, 06(06): 327-333.

目的

探讨重型创伤性脑损伤（TBI）合并骨折（F）患者的血清降钙素基因相关肽（CGRP）水平与病情严重程度及预后的关系。

方法

前瞻性收集2016年6月至2017年6月廊坊市人民医院收治的186例外伤患者和40例健康体检者。男性140例，女性86例，年龄20~73岁，平均（40±12）岁。将研究对象分为4组，创伤性脑损伤合并骨折组（TBI+F）62例、创伤性脑损伤组（TBI）62例、骨折组（F）62例和健康对照组40例（N）。采用酶联免疫吸附法（ELISA）测定血清CGRP水平。ROC曲线预测重型TBI合并骨折患者死亡风险。采用Kaplan-Meier法、Cox回归模型分析重型TBI合并骨折患者独立预后因素。

结果

TBI+F组血清CGRP在不同时间点均高于TBI组、F组和N组（均P<0.05）。通过ROC曲线分析可见血清CGRP水平对重型TBI合并骨折患者死亡风险预测效能较高（AUC=0.785，P<0.05）。多因素Cox分析结果发现，血清CGRP水平（HR=0.793，95% CI：0.688，0.914，P=0.001）是重型TBI合并骨折患者独立预后因素。

结论

重型TBI合并骨折患者血清CGRP水平与疾病严重程度相关，可作为预后不良评估的检测指标。

关键词: 重型创伤性脑损伤, 骨折, 降钙素基因相关肽, 预后
Objective

To explore the relationship between serum calcitonin gene-related peptide (CGRP) level and severity of disease in patients with severe traumatic brain injury (TBI) combined with fracture (F) and its prognosis.

Methods

A total of 186 patients with TBI and 40 healthy controls in our hospital from June 2017 to June 2019 were collected prospectively. There were 140 males and 86 females with an average age of 40±12 years (range, 20-73 years). Patients were divided into four groups, 62 cases in traumatic brain injury combined with fracture group (TBI+F), 62 cases in traumatic brain injury group (TBI), 62 cases in fracture group (F), and 40 healthy persons were allocated in N (normal) group for control. Serum level of CGRP was examined by ELISA. ROC curve was used to predict the risk of death in patients with severe TBI combined with fracture. Kaplan-Meier method and Cox regression model were used to analyze independent prognostic factors in patients with severe TBI combined with fracture.

Results

The serum CGRP levels in the TBI+F group were significantly higher than that in the TBI group, F group and N group at different time points. ROC curve analysis shows that serum CGRP levels are more effective in predicting the death of patients with severe TBI combined with fractures (AUC=0.785, P<0.05). Cox multivariate analysis showed that serum CGRP levels was an independent prognostic factor for patients with severe TBI combined with fracture (HR=0.793, 95% CI: 0.688, 0.914, P=0.001).

Conclusions

The serum CGRP level of patients with severe TBI combined with fracture is related to the severity of the disease, and can be used as a detection indicator for poor prognosis assessment.

Key words: Severe traumatic brain injury, Fractures, Calcitonin gene-related peptide, Prognosis
表1 各组重型创伤性脑损伤合并骨折不同时间点血清CGRP水平（pg/ml，±s）
组别 例数 入院 24 h 72 h 5d 14 d F值 P值
N组 40 45.75±3.66 45.37±5.03 44.65±7.63 45.52±4.42 45.97±4.59 0.369 0.831
F组 62 47.84±5.79 49.80±7.02 52.75±5.73ab 51.80±5.02a 52.23±7.41ab 6.561 <0.001
TBI组 62 50.34±6.67 55.56±5.37a 57.98±6.64ab 56.93±5.07a 53.91±9.21abcd 12.176 <0.001
TBI+F组 62 51.80±4.08 60.76±6.75a 60.03±7.21a 59.27±7.60a 56.77±6.15abcd 19.532 <0.001
表2 各组重型创伤性脑损伤合并骨折血清CGRP两两比较结果
组别 入院 24 h 72 h 5 d 14 d
N组与F组 t=-2.235 t=-3.459 t=-5.753 t=-6.455 t=-4.431
P=0.028 P=0.001 P<0.001 P<0.001 P<0.001
N组与TBI组 t=-4.473 t=-9.581 t=-9.336 t=-11.652 t=-5.042
P<0.001 P<0.001 P<0.001 P<0.001 P<0.001
N组与TBI+F组 t=-7.616 t=-12.359 t=-10.283 t=-11.533 t=-8.634
P<0.001 P<0.001 P<0.001 P<0.001 P<0.001
F组与TBI组 t=-2.225 t=-5.129 t=-4.698 t=-5.659 t=-1.117
P=0.028 P<0.001 P<0.001 P<0.001 P=0.266
F组与TBI+F组 t=-4.403 t=-8.857 t=-6.227 t=-6.457 t=-3.706
P<0.001 P<0.001 P<0.001 P<0.001 P<0.001
TBI组与TBI+F组 t=-1.475 t=-4.740 t=-1.647 t=-2.019 t=-2.029
P=0.143 P<0.001 P=0.102 P=0.046 P=0.045
表3 重型TBI合并骨折患者临床病理指标与血清CGRP水平的关系
变量 例数 CGRP 统计值 P值
年龄     t=-1.100 0.276
<40岁 36 51.3±3.4    
≥40岁 26 52.5±4.9    
性别     t=0.504 0.616
男性 41 52.0±4.3    
女性 21 51.4±3.6    
中线移位距离     t=-1.115 0.269
<5 mm 34 51.2±4.5    
≥5mm 28 52.4±3.6    
GCS     t=-2.699 0.009
≤5分 45 51.0±3.3    
>5分 17 54.0±5.2    
骨折部位     F=0.222 0.881
颅骨 17 51.2±3.3    
髋骨 9 52.2±1.3    
肋骨 13 52.4±5.5    
四肢骨 23 51.8±4.5    
死亡     t=3.598 <0.001
是 16 48.9±3.5    
否 46 52.8±3.8    
图1 血清CGRP水平对重型TBI合并骨折患者死亡预测的ROC曲线
图2 重型TBI合并骨折患者的生存曲线
表4 影响重型TBI合并骨折患者预后的COX回归分析
变量 单因素分析 多因素分析
HR（95% CI） P值 HR（95% CI） P值
年龄 0.996（0.959，1.035） 0.846 — —
性别（女vs男） 0.937（0.326，2.698） 0.904 — —
中线结构移位>5 mm（是vs否） 0.534（0.194，1.469） 0.224 — —
GCS分数 0.477（0.282，0.805） 0.006 0.496（0.284-0.867） 0.014
骨折部位        
四肢骨 1      
髋骨 0.459（0.159，1.328） 0.151 — —
肋骨 0.195（0.024，1.566） 0.124 — —
颅骨 0.131（0.016，1.046） 0.055 — —
CGRP水平 0.768（0.663，0.891） <0.001 0.793（0.688，0.914） 0.001
1
Iaccarino C, Carretta A, Nicolosi F, et al. Epidemiology of severe traumatic brain injury [J]. J Neurosurg Sci, 2018, 62(5): 535-541.
2
Singh R, Humphries T, Mason S, et al. The incidence of anosmia after traumatic brain injury: the SHEFBIT cohort [J]. Brain Inj, 2018, 32(9): 1122-1128.
3
Taylor CA, Bell JM, Breiding MJ. Traumatic brain Injury-Related emergency department visits, hospitalizations, and deaths - United States, 2007 and 2013 [J]. MMWR Surveill Summ, 2017, 66(9): 1-18.
4
Forslund MV, Perrin PB, Røe C, et al. Global outcome trajectories up to 10 years after moderate to severe traumatic brain injury [J]. Front Neurol, 2019, 10: 219.
5
Dikmen S, Machamer J, Manley GT, et al. Functional status examination versus Glasgow outcome scale extended as outcome measures in traumatic brain injuries: how do they compare? [J]. J Neurotrauma, 2019, 36(16): 2423-2429.
6
Van Dijck JT, Reith FC, Van Erp IA, et al. Decision making in very severe traumatic brain injury (Glasgow Coma Scale 3-5): a literature review of acute neurosurgical management [J]. J Neurosurg Sci, 2018, 62(2): 153-177.
7
黄忻涛,闫青云,王士洲,等.颅脑创伤病人S100β,神经元特异性烯醇化酶水平变化及其与炎症因子和凝血指标的相关性研究[J].中西医结合心脑血管病杂志,2020,18(3): 528-531.
8
王航,宋歌,刘永建,等.脑脊液和血浆中tau蛋白及神经颗粒素在急性颅脑损伤患者中检测的临床意义[J].心脑血管病防治,2019,19(6): 520-522.
9
Wang WT, Sun L, Sun CH. PDIA3-regulted inflammation and oxidative stress contribute to the traumatic brain injury (TBI) in mice [J]. Biochem Biophys Res Commun, 2019, 518(4): 657-663.
10
Tringali G, Navarra P. Anti-CGRP and anti-CGRP receptor monoclonal antibodies as antimigraine agents. Potential differences in safety profile postulated on a pathophysiological basis [J]. Peptides, 2019, 116: 16-21.
11
王栋,白雪蕾,吴环立,等.出血性脑卒中病人血浆和脑脊液β-内啡肽、GnRH、NO、CGRP的变化及意义[J].中国临床神经外科杂志,2019,24(11): 669-671,674.
12
Kaiser EA, Rea BJ, Kuburas A, et al. Anti-CGRP antibodies block CGRP-induced diarrhea in mice [J]. Neuropeptides, 2017, 64: 95-99.
13
Chen LX, Zhang WF, Wang M, et al. Relationship of calcitonin gene-related peptide with disease progression and prognosis of patients with severe traumatic brain injury [J]. Neural Regen Res, 2018, 13(10): 1782-1786.
14
Peeters W, Van Den Brande R, Polinder S, et al. Epidemiology of traumatic brain injury in Europe [J]. Acta Neurochir (Wien), 2015, 157(10): 1683-1696.
15
Kumar A, Stoica BA, Loane DJ, et al. Microglial-derived microparticles mediate neuroinflammation after traumatic brain injury [J]. J Neuroinflammation, 2017, 14(1): 47.
16
Li H, Sun J, Du J, et al. Clostridium butyricum exerts a neuroprotective effect in a mouse model of traumatic brain injury via the gut-brain axis [J]. Neurogastroenterol Motil, 2018, 30(5): e13260.
17
Russell AL, Richardson MR, Bauman BM, et al. Differential responses of the HPA axis to mild blast traumatic brain injury in male and female mice [J]. Endocrinology, 2018, 159(6): 2363-2375.
18
Purkayastha S, Stokes M, Bell KR. Autonomic nervous system dysfunction in mild traumatic brain injury: a review of related pathophysiology and symptoms [J]. Brain Inj, 2019, 33(9): 1129-1136.
19
Tapp ZM, Godbout JP, Kokiko-Cochran ON. A tilted axis: maladaptive inflammation and HPA axis dysfunction contribute to Consequences of TBI [J]. Front Neurol, 2019, 10: 345.
20
曾子桓,张灏,陈伟强,等.颅脑损伤后继发性脑损伤发病机制的研究进展[J].中国临床神经外科杂志,2019,24(12): 777-779.
21
李宝,王志军,邢笑源,等.创伤性颅脑损伤患者外周血sTREM-1、MIP-1α水平及与预后的关系[J].疑难病杂志,2019,18(12): 1221-1224,1230.
22
Daoud H, Alharfi I, Alhelali I, et al. Brain injury biomarkers as outcome predictors in pediatric severe traumatic brain injury [J]. Neurocrit Care, 2014, 20(3): 427-435.
23
张振宇.降钙素基因相关肽在创伤性脑损伤加速骨折愈合中的作用机制研究[D].西安:第四军医大学, 2011.
24
González-Hernández A, Marichal-Cancino B, Lozano-Cuenca J, et al. Heteroreceptors modulating CGRP release at neurovascular junction: potential therapeutic implications on Some Vascular-Related diseases [J]. Biomed Res Int, 2016: 2056786.
25
郑林丰,谢应桂,许愿忠.降钙素基因相关肽在神经系统损伤中的作用[J].创伤外科杂志,2006,8(6): 571-573.
26
Diel RJ, Mehra D, Kardon R, et al. Photophobia: shared pathophysiology underlying dry eye disease, migraine and traumatic brain injury leading to central neuroplasticity of the trigeminothalamic pathway [J]. Br J Ophthalmol, 2020: bjophthalmol-2020-316417.
27
Borkum JM. CGRP and brain functioning: cautions for migraine treatment [J]. Headache, 2019, 59(8): 1339-1357.
28
Sorby-Adams AJ, Marcoionni AM, Dempsey ER, et al. The role of neurogenic inflammation in Blood-Brain barrier disruption and development of cerebral oedema following acute central nervous system (CNS) injury [J]. Int J Mol Sci, 2017, 18(8): 1788.
29
Ashina H, Al-Khazali HM, Iljazi A, et al. Low plasma levels of calcitonin gene-related peptide in persistent post-traumatic headache attributed to mild traumatic brain injury [J]. Cephalalgia, 2020, 40(12): 1276-1282.
30
Song Y, Bi L, Zhang ZY, et al. Increased levels of calcitonin gene-related peptide in serum accelerate fracture healing following traumatic brain injury [J]. Mol Med Rep, 2012, 5(2): 432-438.
31
Liang W, Li L, Cui X, et al. Enhanced proliferation and differentiation effects of a CGRP- and Sr-enriched Calcium phosphate cement on bone mesenchymal stem cells [J]. J Appl Biomater Funct Mater, 2016, 14(4): e431-e440.
32
Vignery A, Mccarthy TL. The neuropeptide calcitonin gene-related peptide stimulates insulin-like growth factor I production by primary fetal rat osteoblasts [J]. Bone, 1996, 18(4): 331-335.
33
He H, Chai J, Zhang S, et al. CGRP May regulate bone metabolism through stimulating osteoblast differentiation and inhibiting osteoclast formation [J]. Mol Med Rep, 2016, 13(5): 3977-3984.
34
王诗尧,许少策,师政伟,等.骨重建过程中降钙素基因相关肽与RANK/RANKL/OPG作用机制的研究进展[J].中国修复重建外科杂志,2019,33(4): 511-515.
35
Sullivan PG, Rabchevsky AG, Waldmeier PC, et al. Mitochondrial permeability transition in CNS trauma: cause or effect of neuronal cell death? [J]. J Neurosci Res, 2005, 79(1/2): 231-239.
36
Sutton RL, Lescaudron L, Stein DG. Unilateral cortical contusion injury in the rat: vascular disruption and temporal development of cortical necrosis [J]. J Neurotrauma, 1993, 10(2): 135-149.
37
魏鹏,徐峰,刘聪,等.重型颅脑损伤患者血清淀粉酶水平对患者预后的评估价值[J].中国处方药,2019,17(3): 142-143.
38
Rey C, García-Hernández I, Concha A, et al. Pro-adrenomedullin, pro-endothelin-1, procalcitonin, C-reactive protein and mortality risk in critically ill children: a prospective study [J]. Crit Care, 2013, 17(5): R240.
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