术后认知功能障碍外周血循环生物标志物概述_West China Medical Journal

Authors：

刘海贝 , 朱涛 , 马刚 ,  陈婵

四川大学华西医院麻醉手术中心（成都 610041）;

Corresponding author：

陈婵, Email: xychenchan@gmail.com

Keywords：

术后认知功能障碍; 外周血循环; 生物学标志物

DOI：

10.7507/1002-0179.201604028

Video：

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术后认知功能障碍（postoperative cognitive dysfunction，POCD）是一种麻醉和手术后常见的神经系统并发症，尤其是在老年患者中发病率高，严重影响患者的生活质量和远期转归。目前对 POCD 的诊断主要依靠神经心理学测试，然而这一方法对于 POCD 的诊断通常较晚，因此寻找高特异性和敏感性的生物学标志物对于及时预测、发现和治疗 POCD 至关重要。该文对目前外周血循环中所发现的各类 POCD 生物学标志物，如蛋白质、多肽、脂类、甾体和核酸等及其可能涉及的机制进行了综述。

Citation： 刘海贝, 朱涛, 马刚, 陈婵. 术后认知功能障碍外周血循环生物标志物概述. West China Medical Journal, 2017, 32(11): 1791-1796. doi: 10.7507/1002-0179.201604028 Copy

1.	Tsai TL, Sands LP, Leung JM. An update on postoperative cognitive dysfunction. Adv Anesth, 2010, 28(1): 269-284.
2.	Steinmetz J, Christensen KB, Lund T, et al. Long-term consequences of postoperative cognitive dysfunction. Anesthesiology, 2009, 110(3): 548-555.
3.	Zheng XU, Ma Z, Gu X. Plasma levels of tumor necrosis factor-α in adolescent idiopathic scoliosis patients serve as a predictor for the incidence of early postoperative cognitive dysfunction following orthopedic surgery. Exp Ther Med, 2015, 9(4): 1443-1447.
4.	Li YC, Xi CH, An YF, et al. Perioperative inflammatory response and protein S-100β concentrations - relationship with post-operative cognitive dysfunction in elderly patients. Acta Anaesthesiol Scand, 2012, 56(5): 595-600.
5.	Lin GX, Wang T, Chen MH, et al. Serum high-mobility group box 1 protein correlates with cognitive decline after gastrointestinal surgery. Acta Anaesthesiol Scand, 2014, 58(6): 668-674.
6.	Ji MH, Yuan HM, Zhang GF, et al. Changes in plasma and cerebrospinal fluid biomarkers in aged patients with early postoperative cognitive dysfunction following total hip-replacement surgery. J Anesth, 2013, 27(2): 236-242.
7.	Zhang YH, Guo XH, Zhang QM, et al. Serum CRP and urinary trypsin inhibitor implicate postoperative cognitive dysfunction especially in elderly patients. Int J Neurosci, 2015, 125(7): 501-506.
8.	He HJ, Wang Y, Le Y, et al. Surgery upregulates high mobility group Box-1 and disrupts the blood-brain barrier causing cognitive dysfunction in aged rats. CNS Neurosci Ther, 2012, 18(12): 994-1002.
9.	张媛, 钱燕宁, 斯妍娜, 等. 结直肠手术后认知功能障碍患者血清细胞因子的差异表达. 细胞与分子免疫学杂志, 2015, 31(2): 231-234.
10.	Mack WJ, Ducruet AF, Hickman ZL, et al. Elevation of monocyte chemoattractant protein-1 in patients experiencing neurocognitive decline following carotid endarterectomy. Acta Neurochir (Wien), 2008, 150(8): 779-784; discussion 784.
11.	Xie HH, Huang DH, Zhang S, et al. Relationships between adiponectin and matrix metalloproteinase-9 (MMP-9) serum levels and postoperative cognitive dysfunction in elderly patients after general anesthesia. Aging Clin Exp Res, 2016, 28(6): 1075-1079.
12.	Gaudet JG, Yocum GT, Lee SS, et al. MMP-9 levels in elderly patients with cognitive dysfunction after carotid surgery. J Clin Neurosci, 2010, 17(4): 436-440.
13.	Hovens IB, van Leeuwen BL, Mariani MA, et al. Postoperative cognitive dysfunction and neuroinflammation; cardiac surgery and abdominal surgery are not the same. Brain Behav Immun, 2016, 54: 178-193.
14.	Linstedt U, Meyer O, Kropp P, et al. Serum concentration of S-100 protein in assessment of cognitive dysfunction after general anesthesia in different types of surgery. Acta Anaesthesiol Scand, 2002, 46(4): 384-389.
15.	Jones EL, Gauge N, Nilsen OB, et al. Analysis of neuron-specific enolase and S100B as biomarkers of cognitive decline following surgery in older people. Dement Geriatr Cogn Disord, 2012, 34(5/6): 307-311.
16.	Peng L, Xu L, Ouyang W. Role of peripheral inflammatory markers in postoperative cognitive dysfunction (POCD): a meta-analysis. PLoS One, 2013, 8(11): e79624.
17.	Sun Y, Qin Q, Shang YJ, et al. The accuracy of glial fibrillary acidic protein in acute stroke differential diagnosis: a meta-analysis. Scand J Clin Lab Invest, 2013, 73(8): 601-606.
18.	Rappold T, Laflam A, Hori D, et al. Evidence of an association between brain cellular injury and cognitive decline after non-cardiac surgery. Br J Anaesth, 2016, 116(1): 83-89.
19.	Jessen KR, Thorpe R, Mirsky R. Molecular identity, distribution and heterogeneity of glial fibrillary acidic protein: an immunoblotting and immunohistochemical study of Schwann cells, satellite cells, enteric glia and astrocytes. J Neurocytol, 1984, 13(2): 187-200.
20.	Jiang J, Chen Z, Liang B, et al. Insulin-like growth factor-1 and insulin-like growth factor binding protein 3 and risk of postoperative cognitive dysfunction. Springerplus, 2015, 4: 787.
21.	Vachharajani V, Cunningham C, Yoza B, et al. Adiponectin-deficiency exaggerates sepsis-induced microvascular dysfunction in the mouse brain. Obesity (Silver Spring), 2012, 20(3): 498-504.
22.	Kamogawa K, Kohara K, Tabara Y, et al. Abdominal fat, adipose-derived hormones and mild cognitive impairment: the J-SHIPP study. Dement Geriatr Cogn Disord, 2010, 30(5): 432-439.
23.	Xie Z, Mcauliffe S, Swain CA, et al. Cerebrospinal fluid aβ to tau ratio and postoperative cognitive change. Ann Surg, 2013, 258(2): 364-369.
24.	Evered LA, Silbert BS, Scott DA, et al. Plasma amyloid beta42 and amyloid beta40 levels are associated with early cognitive dysfunction after cardiac surgery. Ann Thorac Surg, 2009, 88(5): 1426-1432.
25.	Dong S, Li CL, Liang WD, et al. Postoperative plasma copeptin levels independently predict delirium and cognitive dysfunction after coronary artery bypass graft surgery. Peptides, 2014, 59(9): 70-74.
26.	Strain JJ, Mcsorley EM, Van Wijngaarden E, et al. Choline status and neurodevelopmental outcomes at 5 years of age in the Seychelles Child Development Nutrition Study. Br J Nutr, 2013, 110(2): 330-336.
27.	Plaschke K, Hauth S, Jansen C, et al. The influence of preoperative serum anticholinergic activity and other risk factors for the development of postoperative cognitive dysfunction after cardiac surgery. J Thorac Cardiovasc Surg, 2013, 145(3): 805-811.
28.	Mu DL, Li LH, Wang DX, et al. High postoperative serum cortisol level is associated with increased risk of cognitive dysfunction early after coronary artery bypass graft surgery: a prospective cohort study. PLoS One, 2013, 8(10): e77637.
29.	Cerejeira J, Batista P, Nogueira V, et al. The stress response to surgery and postoperative delirium: evidence of hypothalamic-pituitary-adrenal axis hyperresponsiveness and decreased suppression of the GH/IGF-1 Axis. J Geriatr Psychiatry Neurol, 2013, 26(3): 185-194.
30.	Yu X, Liu S, Li J, et al. MicroRNA-572 improves early post-operative cognitive dysfunction by down-regulating neural cell adhesion molecule 1. PLoS One, 2015, 10(2): e0118511.
31.	Cai Y, Hu H, Liu P, et al. Association between the apolipoprotein E4 and postoperative cognitive dysfunction in elderly patients undergoing intravenous anesthesia and inhalation anesthesia. Anesthesiology, 2012, 116(1): 84-93.
32.	Saito H, Ogasawara K, Komoribayashi N, et al. Concentration of malondialdehyde-modified low-density lipoprotein in the jugular bulb during carotid endarterectomy correlates with development of postoperative cognitive impairment. Neurosurgery, 2007, 60(6): 1067-1073; discussion 1073-1074.
33.	Yang C, Zhu B, Ding J, et al. Isoflurane anesthesia aggravates cognitive impairment in streptozotocin-induced diabetic rats. Int J Clin Exp Med, 2014, 7(4): 903-910.

1. Tsai TL, Sands LP, Leung JM. An update on postoperative cognitive dysfunction. Adv Anesth, 2010, 28(1): 269-284.
2. Steinmetz J, Christensen KB, Lund T, et al. Long-term consequences of postoperative cognitive dysfunction. Anesthesiology, 2009, 110(3): 548-555.
3. Zheng XU, Ma Z, Gu X. Plasma levels of tumor necrosis factor-α in adolescent idiopathic scoliosis patients serve as a predictor for the incidence of early postoperative cognitive dysfunction following orthopedic surgery. Exp Ther Med, 2015, 9(4): 1443-1447.
4. Li YC, Xi CH, An YF, et al. Perioperative inflammatory response and protein S-100β concentrations - relationship with post-operative cognitive dysfunction in elderly patients. Acta Anaesthesiol Scand, 2012, 56(5): 595-600.
5. Lin GX, Wang T, Chen MH, et al. Serum high-mobility group box 1 protein correlates with cognitive decline after gastrointestinal surgery. Acta Anaesthesiol Scand, 2014, 58(6): 668-674.
6. Ji MH, Yuan HM, Zhang GF, et al. Changes in plasma and cerebrospinal fluid biomarkers in aged patients with early postoperative cognitive dysfunction following total hip-replacement surgery. J Anesth, 2013, 27(2): 236-242.
7. Zhang YH, Guo XH, Zhang QM, et al. Serum CRP and urinary trypsin inhibitor implicate postoperative cognitive dysfunction especially in elderly patients. Int J Neurosci, 2015, 125(7): 501-506.
8. He HJ, Wang Y, Le Y, et al. Surgery upregulates high mobility group Box-1 and disrupts the blood-brain barrier causing cognitive dysfunction in aged rats. CNS Neurosci Ther, 2012, 18(12): 994-1002.
9. 张媛, 钱燕宁, 斯妍娜, 等. 结直肠手术后认知功能障碍患者血清细胞因子的差异表达. 细胞与分子免疫学杂志, 2015, 31(2): 231-234.
10. Mack WJ, Ducruet AF, Hickman ZL, et al. Elevation of monocyte chemoattractant protein-1 in patients experiencing neurocognitive decline following carotid endarterectomy. Acta Neurochir (Wien), 2008, 150(8): 779-784; discussion 784.
11. Xie HH, Huang DH, Zhang S, et al. Relationships between adiponectin and matrix metalloproteinase-9 (MMP-9) serum levels and postoperative cognitive dysfunction in elderly patients after general anesthesia. Aging Clin Exp Res, 2016, 28(6): 1075-1079.
12. Gaudet JG, Yocum GT, Lee SS, et al. MMP-9 levels in elderly patients with cognitive dysfunction after carotid surgery. J Clin Neurosci, 2010, 17(4): 436-440.
13. Hovens IB, van Leeuwen BL, Mariani MA, et al. Postoperative cognitive dysfunction and neuroinflammation; cardiac surgery and abdominal surgery are not the same. Brain Behav Immun, 2016, 54: 178-193.
14. Linstedt U, Meyer O, Kropp P, et al. Serum concentration of S-100 protein in assessment of cognitive dysfunction after general anesthesia in different types of surgery. Acta Anaesthesiol Scand, 2002, 46(4): 384-389.
15. Jones EL, Gauge N, Nilsen OB, et al. Analysis of neuron-specific enolase and S100B as biomarkers of cognitive decline following surgery in older people. Dement Geriatr Cogn Disord, 2012, 34(5/6): 307-311.
16. Peng L, Xu L, Ouyang W. Role of peripheral inflammatory markers in postoperative cognitive dysfunction (POCD): a meta-analysis. PLoS One, 2013, 8(11): e79624.
17. Sun Y, Qin Q, Shang YJ, et al. The accuracy of glial fibrillary acidic protein in acute stroke differential diagnosis: a meta-analysis. Scand J Clin Lab Invest, 2013, 73(8): 601-606.
18. Rappold T, Laflam A, Hori D, et al. Evidence of an association between brain cellular injury and cognitive decline after non-cardiac surgery. Br J Anaesth, 2016, 116(1): 83-89.
19. Jessen KR, Thorpe R, Mirsky R. Molecular identity, distribution and heterogeneity of glial fibrillary acidic protein: an immunoblotting and immunohistochemical study of Schwann cells, satellite cells, enteric glia and astrocytes. J Neurocytol, 1984, 13(2): 187-200.
20. Jiang J, Chen Z, Liang B, et al. Insulin-like growth factor-1 and insulin-like growth factor binding protein 3 and risk of postoperative cognitive dysfunction. Springerplus, 2015, 4: 787.
21. Vachharajani V, Cunningham C, Yoza B, et al. Adiponectin-deficiency exaggerates sepsis-induced microvascular dysfunction in the mouse brain. Obesity (Silver Spring), 2012, 20(3): 498-504.
22. Kamogawa K, Kohara K, Tabara Y, et al. Abdominal fat, adipose-derived hormones and mild cognitive impairment: the J-SHIPP study. Dement Geriatr Cogn Disord, 2010, 30(5): 432-439.
23. Xie Z, Mcauliffe S, Swain CA, et al. Cerebrospinal fluid aβ to tau ratio and postoperative cognitive change. Ann Surg, 2013, 258(2): 364-369.
24. Evered LA, Silbert BS, Scott DA, et al. Plasma amyloid beta42 and amyloid beta40 levels are associated with early cognitive dysfunction after cardiac surgery. Ann Thorac Surg, 2009, 88(5): 1426-1432.
25. Dong S, Li CL, Liang WD, et al. Postoperative plasma copeptin levels independently predict delirium and cognitive dysfunction after coronary artery bypass graft surgery. Peptides, 2014, 59(9): 70-74.
26. Strain JJ, Mcsorley EM, Van Wijngaarden E, et al. Choline status and neurodevelopmental outcomes at 5 years of age in the Seychelles Child Development Nutrition Study. Br J Nutr, 2013, 110(2): 330-336.
27. Plaschke K, Hauth S, Jansen C, et al. The influence of preoperative serum anticholinergic activity and other risk factors for the development of postoperative cognitive dysfunction after cardiac surgery. J Thorac Cardiovasc Surg, 2013, 145(3): 805-811.
28. Mu DL, Li LH, Wang DX, et al. High postoperative serum cortisol level is associated with increased risk of cognitive dysfunction early after coronary artery bypass graft surgery: a prospective cohort study. PLoS One, 2013, 8(10): e77637.
29. Cerejeira J, Batista P, Nogueira V, et al. The stress response to surgery and postoperative delirium: evidence of hypothalamic-pituitary-adrenal axis hyperresponsiveness and decreased suppression of the GH/IGF-1 Axis. J Geriatr Psychiatry Neurol, 2013, 26(3): 185-194.
30. Yu X, Liu S, Li J, et al. MicroRNA-572 improves early post-operative cognitive dysfunction by down-regulating neural cell adhesion molecule 1. PLoS One, 2015, 10(2): e0118511.
31. Cai Y, Hu H, Liu P, et al. Association between the apolipoprotein E4 and postoperative cognitive dysfunction in elderly patients undergoing intravenous anesthesia and inhalation anesthesia. Anesthesiology, 2012, 116(1): 84-93.
32. Saito H, Ogasawara K, Komoribayashi N, et al. Concentration of malondialdehyde-modified low-density lipoprotein in the jugular bulb during carotid endarterectomy correlates with development of postoperative cognitive impairment. Neurosurgery, 2007, 60(6): 1067-1073; discussion 1073-1074.
33. Yang C, Zhu B, Ding J, et al. Isoflurane anesthesia aggravates cognitive impairment in streptozotocin-induced diabetic rats. Int J Clin Exp Med, 2014, 7(4): 903-910.

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