脊髓损伤中的自噬及相关研究进展
摘要
<正>脊髓损伤(spinal cord injury,SCI)是一种严重的神经系统创伤,会导致损伤节段以下肢体功能障碍,不仅给患者本人带来身体和心理的严重伤害,还会给社会带来巨大的经济负担。SCI的常见病因有高处坠落伤、交通事故、重物砸伤、运动损伤等。进入20世纪后半叶,随着我国经济水平的快速发展,SCI的发生率呈现逐年升高趋势,上
引文
1.胥少汀,葛宝丰,徐印坎.实用骨科[M].第4版.郑州:河南科学技术出版社, 2019. 645-646.
2 . Wang ZY, Lin JH, Muharram A, et al. Beclin-1-mediated autophagy protects spinal cord neurons against mechanical injury-induced apoptosis[J]. Apoptosis, 2014, 19(6):933-945.
3 . Lipinski MM, Wu J, Faden AI, et al. Function and mechanisms of autophagy in brain and spinal cord trauma[J]. Antioxid Redox Signal, 2015, 23(6):565-577.
4 . Chen JW, Ni BB, Li B, et al. The responses of autophagy and apoptosis to oxidative stress in nucleus pulposus cells:implications for disc degeneration[J]. Cell Physiol Biochem,2014, 34(4):1175-1189.
5 . Zhang F, Zhao X, Shen H, et al. Molecular mechanisms of cell death in intervertebral disc degeneration(review)[J]. Int J Mol Med, 2016, 37(6):1439-1448.
6 . Zhang SJ, Yang W, Wang C, et al. Autophagy:a doubleedged sword in intervertebral disk degeneration[J]. Clin Chim Acta, 2016, 457:27-35.
7 . Feng C, Yang M, Lan M, et al. ROS:crucial intermediators in the pathogenesis of intervertebral disc degeneration[J].Spinal Cord, 2017, 55(9):834-839.
8 . Chu R, Wang J, Bi Y, et al. The kinetics of autophagy in the lung following acute spinal cord injury in rats[J]. Spine,2018, 18(5):845-856.
9 . Yu D, Li M, Ni B, et al. Induction of neuronal mitophagy in acute spinal cord injury in rats[J]. Neurotox Res, 2013, 24(4):512-522.
10 . Zhou K, Sansur CA, Xu H, et al. The Temporal pattern,flux, and function of autophagy in spinal cord injury[J]. Int J Mol Sci, 2017, 18(2):466.
11 .侯红平.自噬通过抑制凋亡促进急性脊髓损伤后神经修复的作用机制研究[D].南开大学. 2014.
12 . Schffner I, Minakaki G, Khan MA, et al. FoxO function is essential for maintenance of autophagic flux and neuronal morphogenesis in adult neurogenesis[J]. Neuron, 2018, 99(6):1188-1203.
13 . Boland B, Yu WH, Corti O, et al. Promoting the clearance of neurotoxic proteins in neurodegenerative disorders of ageing[J]. Nat Rev Drug Discov, 2018, 17(9):660-688.
14 . Ye W, Zhu W, Xu K, et al. Increased macroautophagy in the pathological process of intervertebral disc degeneration in rats[J]. Connect Tissue Res, 2013, 54(1):22-28.
15 . Ye W, Xu K, Huang D, et al. Age-related increases of macroautophagy and chaperone-mediated autophagy in rat nucleus pulposus[J]. Connect Tissue Res, 2011, 52(6):472-478.
16 . Shi C, Wu H, Du D, et al. Nicotinamide phosphoribosyltransferase inhibitor APO866 prevents IL-1β-induced human nucleus pulposus cell degeneration via autophagy[J]. Cell Physiol Biochem, 2018, 49(6):2463-2482.
17 . Fujita S, Sakurai M, Baba H, et al. Autophagy-mediated stress response in motor neurons after hypothermic spinal cord ischemia in rabbits[J]. J Vasc Surg, 2015, 62(5):1312-1319.
18 . Tanabe F, Yone K, Kawabata N, et al. Accumulation of P62in degenerated spinal cord under chronic mechanical compression:functional analysis of P62 and autophagy in hypoxic neuronal cells[J]. Autophagy, 2011, 7(12):1462-1471.
19 . Kanno H, Ozawa H, Sekiguchi A, et al. Induction of autophagy and autophagic cell death in damaged neural tissue after acute spinal cord injury in mice[J]. Spine(Phila Pa1976), 2011, 36(22):E1427-1434.
20 . Hou H, Zhang L, Zhang L, et al. Acute spinal cord injury in rats should target activated autophagy[J]. J Neurosurg Spine, 2014, 20(5):568-577.
21 . Mu觡oz-Galdeano T, Reigada D, Del魣guila魣, et al. Cell specific changes of autophagy in a mouse model of contusive spinal cord injury[J]. Front Cell Neurosci, 2018, 12:164.
22 . Hao HH, Wang L, Guo ZJ, et al. Valproic acid reduces autophagy and promotes functional recovery after spinal cord injury in rats[J]. Neurosci Bull, 2013, 29:484-492.
23 . Wang P, Xie ZD, Xie CN, et al. AMP-activated protein kinase-dependent induction of autophagy by erythropoietin protects against spinal cord injury in rats[J]. CNS Neurosci Ther, 2018, 24(12):1185-1195.
24 . Hu J, Han H, Cao P, et al. Resveratrol improves neuron protection and functional recovery through enhancement of autophagy after spinal cord injury in mice[J]. Am J Transl Res, 2017, 9(10):4607-4616.
25 . Lin CW, Chen B, Huang KL, et al. Inhibition of autophagy by estradiol promotes locomotor recovery after spinal cord injury in rats[J]. Neurosci Bull, 2016, 32(2):137-144.
26 . Li XG, Du JH, Lu Y, et al. Neuroprotective effects of rapamycin on spinal cord injury in rats by increasing autophagy and Akt signaling[J]. Neural Regen Res, 2019, 14(4):721-727.
27 . Siracusa R, Paterniti I, Bruschetta G, et al. The association of palmitoylethanolamide with luteolin decreases autophagy in spinal cord injury[J]. Mol Neurobiol, 2016, 53(6):3783-3792.
28 . Fang B, Li XQ, Bao NR, et al. Role of autophagy in the bimodal stage after spinal cord ischemia reperfusion injury in rats[J]. Neuroscience, 2016, 328:107-116.
29 . Wei X, Zhou Z, Li L, et al. Intrathecal injection of 3-methyladenine reduces neuronal damage and promotes functional recovery via autophagy attenuation after spinal cord ischemia/reperfusion injury in rats[J]. Biol Pharm Bull, 2016,39(5):665-673.
30 . Li W, Yang Y, Ba Z, et al. MicroRNA-93 regulates hypoxia-induced autophagy by targeting ULK1[J]. Oxid Med Cell Longev, 2017, 2017:2709053. doi:10.1155/2017/2709053.Epub 2017 Oct 3.
31 . Guo Y, Wang F, Li H, et al. Metformin protects against spinal cord injury by regulating utophagy via the mTOR signaling pathway[J]. CNS Neurosci Ther, 2018, 24(12):1185-1195.
32 . Wang C, Liu C, Gao K, et al. Metformin preconditioning provide neuroprotection through enhancement of autophagy and suppression of inflammation and apoptosis after spinal cord injury[J]. Biochem Biophys Res Commun, 2016, 477(4):534-540.
33 . Tong M, He Z, Lin X, et al. Lithium chloride contributes to blood-spinal cord barrier integrity and functional recovery from spinal cord injury by stimulating autophagic flux[J].Biochem Biophys Res Commun, 2018, 495(4):2525-2531.
34 . Liu P, Zhang Z, Wang Q, et al. Lithium chloride facilitates autophagy following spinal cord injury via ERK-dependent pathway[J]. Neurotox Res, 2017, 32(4):535-543.
35 . Feng T, Yin Q, Weng ZL, et al. Rapamycin ameliorates neuropathic pain by activating autophagy and inhibiting interleukin-1βin the rat spinal cord[J]. J Huazhong Univ Sci Technolog Med Sci, 2014, 34(6):830-837.
36 . Tang P, Hou H, Zhang L, et al. Autophagy reduces neuronal damage and promotes locomotor recovery via inhibition of apoptosis after spinal cord injury in rats[J]. Mol Neurobiol,2014, 49(1):276-287.
37 . Sekiguchi A, Kanno H, Ozawa H, et al. Rapamycin promotes autophagy and reduces neural tissue damage and locomotor impairment after spinal cord injury in mice[J]. J Neurotrauma, 2012, 29(5):946-956.
38 . Li Q, Gao S, Kang Z, et al. Rapamycin enhances mitophagy and attenuates apoptosis after spinal ischemia-reperfusion injury[J]. Front Neurosci, 2018, 12:865.
39 . Meng HY, Shao DC, Li H, et al. Resveratrol improves neurological outcome and neuroinflammation following spinal cord injury through enhancing autophagy involving the AMPK/mTOR pathway[J]. Mol Med Rep, 2018, 18(2):2237-2244.
40 . Wang P, Jiang L, Zhou N, et al. Resveratrol ameliorates autophagic flux to promote functional recovery in rats after spinal cord injury[J]. Oncotarget, 2018, 9(9):8427-8440.
41 . Bai L, Mei X, Shen Z, et al. Netrin-1 improves functional recovery through autophagy regulation by activating the AMPK/mTOR signaling pathway in rats with spinal cord injury[J]. Sci Rep, 2017, 7:42288.
42 . Bai L, Mei X, Wang Y, et al. The role of Netrin-1 in improving functional recovery through autophagy stimulation following spinal cord injury in rats[J]. Front Cell Neurosci,2017, 11:350.
43 . Gao S, Zhang ZM, Shen ZL, et al. Atorvastatin activates autophagy and promotes neurological function recovery after spinal cord injury[J]. Neural Regen Res, 2016, 11(6):977-982.
44 . Gao K, Wang G, Wang Y, et al. Neuroprotective effect of simvastatin via inducing the autophagy on spinal cord injury in the rat model[J]. Biomed Res Int, 2015, 2015:260161.
45 . Li L, Jiang HK, Li YP, et al. Hydrogen sulfide protects spianl cord and induces autophagy via miR-30c in a rat model of spianl cord ischemia-reperfusion injury[J]. J Biomed Sci, 2015, 22(1):50.
46 . Seo JY, Kim YH, Kim JW, et al. Effects of therapeutic hypothermia on apoptosis and autophagy after spinal cord injury in rats[J]. Spine(Phila Pa 1976), 2015, 40(12):883-890.
47 . Chen HC, Fong TH, Lee AW, et al. Autophagy is activated in injured neurons and inhibited by methylprednisolone after experimental spinal cord injury[J]. Spine(Phila Pa 1976),2012, 37(6):470-475.
48 . Teixeira WGJ, Cristante AF, Marcon RM, et al. Granulocyte colony-stimulating factor combined with methylprednisolone improves functional outcomes in rats with experimental acute spinal cord injury[J]. Clinics(Sao Paulo), 2018, 73:e235.
49 . Wang P, Lin C, Wu S, et al. Inhibition of autophagy is involved in the protective effects of ginsenoside Rb1 on spinal cord injury[J]. Cell Mol Neurobiol, 2018, 38(3):679-690.
50 . Li H, Zhang Q, Yang X, et al. PPAR-γagonist rosiglitazone reduces autophagy and promotes functional recovery in experimental traumaticspinal cord injury[J]. Neurosci Lett,2017, 650:89-96.
2 . Wang ZY, Lin JH, Muharram A, et al. Beclin-1-mediated autophagy protects spinal cord neurons against mechanical injury-induced apoptosis[J]. Apoptosis, 2014, 19(6):933-945.
3 . Lipinski MM, Wu J, Faden AI, et al. Function and mechanisms of autophagy in brain and spinal cord trauma[J]. Antioxid Redox Signal, 2015, 23(6):565-577.
4 . Chen JW, Ni BB, Li B, et al. The responses of autophagy and apoptosis to oxidative stress in nucleus pulposus cells:implications for disc degeneration[J]. Cell Physiol Biochem,2014, 34(4):1175-1189.
5 . Zhang F, Zhao X, Shen H, et al. Molecular mechanisms of cell death in intervertebral disc degeneration(review)[J]. Int J Mol Med, 2016, 37(6):1439-1448.
6 . Zhang SJ, Yang W, Wang C, et al. Autophagy:a doubleedged sword in intervertebral disk degeneration[J]. Clin Chim Acta, 2016, 457:27-35.
7 . Feng C, Yang M, Lan M, et al. ROS:crucial intermediators in the pathogenesis of intervertebral disc degeneration[J].Spinal Cord, 2017, 55(9):834-839.
8 . Chu R, Wang J, Bi Y, et al. The kinetics of autophagy in the lung following acute spinal cord injury in rats[J]. Spine,2018, 18(5):845-856.
9 . Yu D, Li M, Ni B, et al. Induction of neuronal mitophagy in acute spinal cord injury in rats[J]. Neurotox Res, 2013, 24(4):512-522.
10 . Zhou K, Sansur CA, Xu H, et al. The Temporal pattern,flux, and function of autophagy in spinal cord injury[J]. Int J Mol Sci, 2017, 18(2):466.
11 .侯红平.自噬通过抑制凋亡促进急性脊髓损伤后神经修复的作用机制研究[D].南开大学. 2014.
12 . Schffner I, Minakaki G, Khan MA, et al. FoxO function is essential for maintenance of autophagic flux and neuronal morphogenesis in adult neurogenesis[J]. Neuron, 2018, 99(6):1188-1203.
13 . Boland B, Yu WH, Corti O, et al. Promoting the clearance of neurotoxic proteins in neurodegenerative disorders of ageing[J]. Nat Rev Drug Discov, 2018, 17(9):660-688.
14 . Ye W, Zhu W, Xu K, et al. Increased macroautophagy in the pathological process of intervertebral disc degeneration in rats[J]. Connect Tissue Res, 2013, 54(1):22-28.
15 . Ye W, Xu K, Huang D, et al. Age-related increases of macroautophagy and chaperone-mediated autophagy in rat nucleus pulposus[J]. Connect Tissue Res, 2011, 52(6):472-478.
16 . Shi C, Wu H, Du D, et al. Nicotinamide phosphoribosyltransferase inhibitor APO866 prevents IL-1β-induced human nucleus pulposus cell degeneration via autophagy[J]. Cell Physiol Biochem, 2018, 49(6):2463-2482.
17 . Fujita S, Sakurai M, Baba H, et al. Autophagy-mediated stress response in motor neurons after hypothermic spinal cord ischemia in rabbits[J]. J Vasc Surg, 2015, 62(5):1312-1319.
18 . Tanabe F, Yone K, Kawabata N, et al. Accumulation of P62in degenerated spinal cord under chronic mechanical compression:functional analysis of P62 and autophagy in hypoxic neuronal cells[J]. Autophagy, 2011, 7(12):1462-1471.
19 . Kanno H, Ozawa H, Sekiguchi A, et al. Induction of autophagy and autophagic cell death in damaged neural tissue after acute spinal cord injury in mice[J]. Spine(Phila Pa1976), 2011, 36(22):E1427-1434.
20 . Hou H, Zhang L, Zhang L, et al. Acute spinal cord injury in rats should target activated autophagy[J]. J Neurosurg Spine, 2014, 20(5):568-577.
21 . Mu觡oz-Galdeano T, Reigada D, Del魣guila魣, et al. Cell specific changes of autophagy in a mouse model of contusive spinal cord injury[J]. Front Cell Neurosci, 2018, 12:164.
22 . Hao HH, Wang L, Guo ZJ, et al. Valproic acid reduces autophagy and promotes functional recovery after spinal cord injury in rats[J]. Neurosci Bull, 2013, 29:484-492.
23 . Wang P, Xie ZD, Xie CN, et al. AMP-activated protein kinase-dependent induction of autophagy by erythropoietin protects against spinal cord injury in rats[J]. CNS Neurosci Ther, 2018, 24(12):1185-1195.
24 . Hu J, Han H, Cao P, et al. Resveratrol improves neuron protection and functional recovery through enhancement of autophagy after spinal cord injury in mice[J]. Am J Transl Res, 2017, 9(10):4607-4616.
25 . Lin CW, Chen B, Huang KL, et al. Inhibition of autophagy by estradiol promotes locomotor recovery after spinal cord injury in rats[J]. Neurosci Bull, 2016, 32(2):137-144.
26 . Li XG, Du JH, Lu Y, et al. Neuroprotective effects of rapamycin on spinal cord injury in rats by increasing autophagy and Akt signaling[J]. Neural Regen Res, 2019, 14(4):721-727.
27 . Siracusa R, Paterniti I, Bruschetta G, et al. The association of palmitoylethanolamide with luteolin decreases autophagy in spinal cord injury[J]. Mol Neurobiol, 2016, 53(6):3783-3792.
28 . Fang B, Li XQ, Bao NR, et al. Role of autophagy in the bimodal stage after spinal cord ischemia reperfusion injury in rats[J]. Neuroscience, 2016, 328:107-116.
29 . Wei X, Zhou Z, Li L, et al. Intrathecal injection of 3-methyladenine reduces neuronal damage and promotes functional recovery via autophagy attenuation after spinal cord ischemia/reperfusion injury in rats[J]. Biol Pharm Bull, 2016,39(5):665-673.
30 . Li W, Yang Y, Ba Z, et al. MicroRNA-93 regulates hypoxia-induced autophagy by targeting ULK1[J]. Oxid Med Cell Longev, 2017, 2017:2709053. doi:10.1155/2017/2709053.Epub 2017 Oct 3.
31 . Guo Y, Wang F, Li H, et al. Metformin protects against spinal cord injury by regulating utophagy via the mTOR signaling pathway[J]. CNS Neurosci Ther, 2018, 24(12):1185-1195.
32 . Wang C, Liu C, Gao K, et al. Metformin preconditioning provide neuroprotection through enhancement of autophagy and suppression of inflammation and apoptosis after spinal cord injury[J]. Biochem Biophys Res Commun, 2016, 477(4):534-540.
33 . Tong M, He Z, Lin X, et al. Lithium chloride contributes to blood-spinal cord barrier integrity and functional recovery from spinal cord injury by stimulating autophagic flux[J].Biochem Biophys Res Commun, 2018, 495(4):2525-2531.
34 . Liu P, Zhang Z, Wang Q, et al. Lithium chloride facilitates autophagy following spinal cord injury via ERK-dependent pathway[J]. Neurotox Res, 2017, 32(4):535-543.
35 . Feng T, Yin Q, Weng ZL, et al. Rapamycin ameliorates neuropathic pain by activating autophagy and inhibiting interleukin-1βin the rat spinal cord[J]. J Huazhong Univ Sci Technolog Med Sci, 2014, 34(6):830-837.
36 . Tang P, Hou H, Zhang L, et al. Autophagy reduces neuronal damage and promotes locomotor recovery via inhibition of apoptosis after spinal cord injury in rats[J]. Mol Neurobiol,2014, 49(1):276-287.
37 . Sekiguchi A, Kanno H, Ozawa H, et al. Rapamycin promotes autophagy and reduces neural tissue damage and locomotor impairment after spinal cord injury in mice[J]. J Neurotrauma, 2012, 29(5):946-956.
38 . Li Q, Gao S, Kang Z, et al. Rapamycin enhances mitophagy and attenuates apoptosis after spinal ischemia-reperfusion injury[J]. Front Neurosci, 2018, 12:865.
39 . Meng HY, Shao DC, Li H, et al. Resveratrol improves neurological outcome and neuroinflammation following spinal cord injury through enhancing autophagy involving the AMPK/mTOR pathway[J]. Mol Med Rep, 2018, 18(2):2237-2244.
40 . Wang P, Jiang L, Zhou N, et al. Resveratrol ameliorates autophagic flux to promote functional recovery in rats after spinal cord injury[J]. Oncotarget, 2018, 9(9):8427-8440.
41 . Bai L, Mei X, Shen Z, et al. Netrin-1 improves functional recovery through autophagy regulation by activating the AMPK/mTOR signaling pathway in rats with spinal cord injury[J]. Sci Rep, 2017, 7:42288.
42 . Bai L, Mei X, Wang Y, et al. The role of Netrin-1 in improving functional recovery through autophagy stimulation following spinal cord injury in rats[J]. Front Cell Neurosci,2017, 11:350.
43 . Gao S, Zhang ZM, Shen ZL, et al. Atorvastatin activates autophagy and promotes neurological function recovery after spinal cord injury[J]. Neural Regen Res, 2016, 11(6):977-982.
44 . Gao K, Wang G, Wang Y, et al. Neuroprotective effect of simvastatin via inducing the autophagy on spinal cord injury in the rat model[J]. Biomed Res Int, 2015, 2015:260161.
45 . Li L, Jiang HK, Li YP, et al. Hydrogen sulfide protects spianl cord and induces autophagy via miR-30c in a rat model of spianl cord ischemia-reperfusion injury[J]. J Biomed Sci, 2015, 22(1):50.
46 . Seo JY, Kim YH, Kim JW, et al. Effects of therapeutic hypothermia on apoptosis and autophagy after spinal cord injury in rats[J]. Spine(Phila Pa 1976), 2015, 40(12):883-890.
47 . Chen HC, Fong TH, Lee AW, et al. Autophagy is activated in injured neurons and inhibited by methylprednisolone after experimental spinal cord injury[J]. Spine(Phila Pa 1976),2012, 37(6):470-475.
48 . Teixeira WGJ, Cristante AF, Marcon RM, et al. Granulocyte colony-stimulating factor combined with methylprednisolone improves functional outcomes in rats with experimental acute spinal cord injury[J]. Clinics(Sao Paulo), 2018, 73:e235.
49 . Wang P, Lin C, Wu S, et al. Inhibition of autophagy is involved in the protective effects of ginsenoside Rb1 on spinal cord injury[J]. Cell Mol Neurobiol, 2018, 38(3):679-690.
50 . Li H, Zhang Q, Yang X, et al. PPAR-γagonist rosiglitazone reduces autophagy and promotes functional recovery in experimental traumaticspinal cord injury[J]. Neurosci Lett,2017, 650:89-96.