高压氧对大鼠脊髓损伤后蛋白激酶R样内质网激酶表达和运动功能的影响

doi:10.3969/j.issn.1006-9771.2018.12.007

《中国康复理论与实践》 ›› 2018, Vol. 24 ›› Issue (12): 1393-1397.doi: 10.3969/j.issn.1006-9771.2018.12.007

高压氧对大鼠脊髓损伤后蛋白激酶R样内质网激酶表达和运动功能的影响

应新旺, 陈晓龙, 谷鹏鹏, 李思思, 蒋松鹤

温州医科大学附属第二医院康复医学中心,浙江温州市 325027

收稿日期:2018-05-04 修回日期:2018-06-21 出版日期:2018-12-25 发布日期:2019-01-04
通讯作者: 蒋松鹤。E-mail: 863191168@qq.com
作者简介:应新旺(1993-),男,汉族,浙江平阳县人,硕士研究生,主要研究方向：脊柱与骨关节。
基金资助:
浙江省卫生厅科研基金项目(No. 2017KY482)

Effect of Hyperbaric Oxygen on Protein Kinase R-like ER Kinase Expression and Motor Function in Rats with Spinal Cord Injury

YING Xin-wang, CHEN Xiao-long, GU Peng-peng, LI Si-si, JIANG Song-he

The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China

Received:2018-05-04 Revised:2018-06-21 Published:2018-12-25 Online:2019-01-04
Contact: JIANG Song-he. E-mail: 863191168@qq.com
Supported by:
Zhejiang Health Department Research Foudation (No. 2017KY482)

摘要/Abstract

摘要： 目的观察高压氧对脊髓损伤大鼠行为学、组织形态学以及蛋白激酶R样内质网激酶(PERK)表达的影响,探讨高压氧治疗脊髓损伤大鼠的作用机制。方法将36只雄性Sprague-Dawley大鼠随机分为正常组(n = 9)、假手术组(n = 9)、模型组(n = 9)和高压氧组(n = 9)。正常组不做任何处理;假手术组仅行椎板切除,不予脊髓打击;其余两组采用改良Allen法建立大鼠脊髓损伤模型,高压氧组于术后6 h开始,给予纯氧治疗连续7 d,每天1次。各组于术前(0 h)及术后6 h、3 d、7 d进行BBB运动功能评分。术后7 d处死大鼠,提取各组损伤区脊髓1.5 cm,采用HE染色法观察损伤脊髓区域组织形态结构的变化;采用Western blotting检测脊髓组织中PERK蛋白表达量。结果正常组和假手术组均无神经功能损伤症状;术后3 d和7 d,模型组BBB评分低于假手术组(P < 0.05);术后7 d,高压氧组BBB评分高于模型组(P < 0.05)。正常组和假手术组均未见明显的结构异常;模型组损伤脊髓区域可见胞体肿胀,细胞结构模糊,间隙增大,胞核固缩溶解等病理结构;与模型组相比,高压氧治疗组组织损伤情况明显好转。术后7 d,模型组PERK表达明显高于假手术组(P < 0.01),高压氧组低于模型组(P < 0.05)。结论高压氧可以降低受损脊髓PERK蛋白的表达,促进大鼠后肢运动功能恢复。

关键词: 脊髓损伤, 高压氧, 蛋白激酶R样内质网激酶, 大鼠

Abstract: Objective To investigate the effect of hyperbaric oxygen (HBO) on the behaviors, organizational morphology and the expression of protein kinase R-like ER kinase (PERK) in rats with spinal cord injury. Methods Thirty-six male Sprague-Dawley rats were randomly divided into normal group, sham group, model group and HBO group, with nine cases in each group. The normal group did not receive any treatment, the sham group received only laminectomy, and the other two groups were established spinal cord injury model with modified Allen's method. Six hours after operation, the model group was treated with regular air, and HBO group received HBO treatment for seven days. The recovery of locomotor function was evaluated by BBB (Basso Beattie and Bresnahan) on the day before operation and six hours, three days, seven days after operation. HE staining was used to observe the change of tissue morphology in injured spinal cord, and the expression of PERK in spinal cord was detected by Western blotting. Results There was no neurological deficit in the normal group and the sham group. The neurological score was lower in the model group than in the sham group three days and seven days after operation (P < 0.05), and was higher in HBO group than in the model group seven days after operation (P < 0.05). There was no obvious structural change in the normal group and the sham group, however, the model group showed swelling cells, condensed cytoplasm, and nucleus pycnosis hyperchromatic, and the HBO group showed slighter swelling cell compared with the model group. The expression of PERK was higher in the model group than in the sham group, and was lower in HBO group than in the model group seven days after operation (P < 0.05). Conclusion HBO could reduce the expression of PERK in the injured spinal cord, and improve the recovery of hind limb locomotor function in spinal cord injury rats.

Key words: spinal cord injury, hyperbaric oxygen, protein kinase R-like ER kinase, rats

中图分类号:

R651.2

应新旺, 陈晓龙, 谷鹏鹏, 李思思, 蒋松鹤. 高压氧对大鼠脊髓损伤后蛋白激酶R样内质网激酶表达和运动功能的影响[J]. 《中国康复理论与实践》, 2018, 24(12): 1393-1397.

YING Xin-wang, CHEN Xiao-long, GU Peng-peng, LI Si-si, JIANG Song-he. Effect of Hyperbaric Oxygen on Protein Kinase R-like ER Kinase Expression and Motor Function in Rats with Spinal Cord Injury[J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2018, 24(12): 1393-1397.

参考文献

[1] Lv ZR, Liu XH.The roles of protein kinase R-like ER kinase signal pathway in endoplasmic reticulum stress[J]. [in Chinese]. Sheng Li Ke Xue Jin Zhan, 2011, 42(2): 154-157.
[2] Wang P, Li J, Tao J, et al.The luminal domain of the ER stress sensor protein PERK binds misfolded proteins and thereby triggers PERK oligomerization[J]. J Biol Chem, 2018, 293(11): 4110-4121.
[3] Scheuner D, Song B, McEwen E, et al. Translational control is required for the unfolded protein response and in vivo glucose homeostasis[J]. Mol Cell, 2001, 7(6): 1165-1176.
[4] Wang C, Guan Y, Yang J.Cytokines in the progression of pancreatic beta-cell dysfunction[J]. Int J Endocrinol, 2010, 2010: 515136.
[5] Fang F, Gong PS, Song XF, et al.Low-dose radiation induces endoplasmic reticulum stress and activates PERK-CHOP signaling pathway in mouse testicular cells[J]. [in Chinese]. Zhonghua Nan Ke Xue, 2012, 18(9): 777-782.
[6] Lee H, Noh JY, Oh Y, et al.IRE1 plays an essential role in ER stress-mediated aggregation of mutant huntingtin via the inhibition of autophagy flux[J]. Hum Mol Genet, 2012, 21(1): 101-114.
[7] He Z, Zhou Y, Huang Y, et al.Dl-3-n-butylphthalide improves functional recovery in rats with spinal cord injury by inhibiting endoplasmic reticulum stress-induced apoptosis[J]. Am J Transl Res, 2017, 9(3): 1075-1087.
[8] 于正道. 高压氧综合治疗脊髓损伤64例疗效分析[J]. 中华航海医学与高气压医学杂志, 2013, 20(6): 421-422.
[9] Tan JW, Zhang F, Liu HJ, et al.Hyperbaric oxygen ameliorated the lesion scope and nerve function in acute spinal cord injury patients: A retrospective study[J]. Clin Biochem, 2018, 53: 1-7.
[10] Khuyagbaatar B, Kim K, Kim YH.Conversion equation between the drop height in the new york university impactor and the impact force in the infinite horizon impactor in the contusion spinal cord injury model[J]. J Neurotrauma, 2015, 32(24): 1987-1993.
[11] Basso DM, Beattie MS, Bresnahan JC.A sensitive and reliable locomotor rating scale for open field testing in rats[J]. J Neurotrauma, 1995, 12(1): 1-21.
[12] Houle JD, Cote MP.Axon regeneration and exercise-dependent plasticity after spinal cord injury[J]. Ann N Y Acad Sci, 2013, 1279: 154-163.
[13] Dumont RJ, Okonkwo DO, Verma S, et al.Acute spinal cord injury, part I: pathophysiologic mechanisms[J]. Clin Neuropharmacol, 2001, 24(5): 254-264.
[14] Kwon BK, Tetzlaff W, Grauer JN, et al.Pathophysiology and pharmacologic treatment of acute spinal cord injury[J]. Spine J, 2004, 4(4): 451-464.
[15] Schilero GJ, Bauman WA, Radulovic M.Traumatic spinal cord injury: pulmonary physiologic principles and management[J]. Clin Chest Med, 2018, 39(2): 411-425.
[16] 李红玲,马维. 高压氧在骨科疾病中的应用研究进展[J]. 中国康复医学杂志, 2014, 29(10): 999-1002.
[17] 孙文志,鲁世保. 高压氧治疗脊髓损伤机制的研究进展[J]. 中国脊柱脊髓杂志 2014, 24(12): 1116-1119.
[18] Vince JE, Wong WW, Gentle I, et al.Inhibitor of apoptosis proteins limit RIP3 kinase-dependent interleukin-1 activation[J]. Immunity, 2012, 36(2): 215-227.
[19] Liu X, Yang J, Li Z, et al.Hyperbaric oxygen treatment protects against spinal cord injury by inhibiting endoplasmic reticulum stress in rats[J]. Spine (Phila Pa 1976), 2015, 40(24): E1276-E1283.
[20] Hetz C.The unfolded protein response: controlling cell fate decisions under ER stress and beyond[J]. Nat Rev Mol Cell Biol, 2012, 13(2): 89-102.
[21] Bernales S, Papa FR, Walter P.Intracellular signaling by the unfolded protein response[J]. Annu Rev Cell Dev Biol, 2006, 22: 487-508.
[22] 张嘉宾,张盼盼,王红阳,等. 磷酸化蛋白激酶样内质网激酶、C/EBP同源蛋白在慢性间歇低氧大鼠肺组织中的表达变化及意义[J]. 中国现代医学杂志, 2016, 26(15): 38-43.
[23] Liu Z, Lv Y, Zhao N, et al.Protein kinase R-like ER kinase and its role in endoplasmic reticulum stress-decided cell fate[J]. Cell Death Dis, 2015, 6: e1822.
[24] Schonthal AH.Pharmacological targeting of endoplasmic reticulum stress signaling in cancer[J]. Biochem Pharmacol, 2013, 85(5): 653-666.
[25] Hirsch I, Weiwad M, Prell E, et al.ERp29 deficiency affects sensitivity to apoptosis via impairment of the ATF6-CHOP pathway of stress response[J]. Apoptosis, 2014, 19(5): 801-815.
[26] Wang XZ, Ron D.Stress-induced phosphorylation and activation of the transcription factor CHOP (GADD153) by p38 MAP Kinase[J]. Science, 1996, 272(5266): 1347-1349.
[27] Yin J, Gu L, Wang Y, et al.Rapamycin improves palmitate-induced ER stress/NF kappa B pathways associated with stimulating autophagy in adipocytes[J]. Mediators Inflamm, 2015: 272313.
[28] Wang L, Li W, Kang Z, et al.Hyperbaric oxygen preconditioning attenuates early apoptosis after spinal cord ischemia in rats[J]. J Neurotrauma, 2009, 26(1): 55-66.

高压氧对大鼠脊髓损伤后蛋白激酶R样内质网激酶表达和运动功能的影响

Effect of Hyperbaric Oxygen on Protein Kinase R-like ER Kinase Expression and Motor Function in Rats with Spinal Cord Injury

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