隔日限食疗法对脊髓损伤大鼠的保护作用及其机制

doi:10.3969/j.issn.1006-9771.2018.02.007

《中国康复理论与实践》 ›› 2018, Vol. 24 ›› Issue (2): 153-159.doi: 10.3969/j.issn.1006-9771.2018.02.007

隔日限食疗法对脊髓损伤大鼠的保护作用及其机制

何宇¹, 张安仁², 孙年怡², 王文春², 王志强¹, 田丽君¹, 邹文晨¹, 张志强¹

1.中国医科大学附属盛京医院康复中心,辽宁沈阳市 110134;
2.中国人民解放军成都总医院康复医学科,四川成都市 610083

收稿日期:2017-12-11 修回日期:2018-01-29 出版日期:2018-02-25 发布日期:2018-03-02
通讯作者: 何宇。E-mail: whyspace@hotmail.com
作者简介:何宇(1987-),男,汉族,辽宁沈阳市人,硕士,康复治疗师,主要研究方向：物理治疗的循证医学研究及应用。
基金资助:
国家自然科学基金面上项目(No. 81674044)

Protective Effect and Mechanism of Every-other-day Fasting on Rats with Spinal Cord Injury

HE Yu¹, ZHANG An-ren², SUN Nian-yi², WANG Wen-chun², WANG Zhi-qiang¹, TIAN Li-jun¹, ZOU Wen-chen¹, ZHANG Zhi-qiang¹

1. Rehabilitation Center, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110134, China;
2. Department of Rehabilitation Medicine, Chengdu General Hospital of Chinese People's Liberation Army, Chengdu, Sichuan 610083, China

Received:2017-12-11 Revised:2018-01-29 Published:2018-02-25 Online:2018-03-02
Contact: HE Yu. E-mail:whyspace@hotmail.com
Supported by:
; Supported by National Natural Science Foundation of China (General) (No. 81674044)

摘要/Abstract

摘要： 目的探讨隔日限食(EODF)对脊髓损伤大鼠脊髓组织病理变化和运动功能恢复的影响及其相关机制。方法将36只Sprague-Dawley大鼠随机分为假手术组、假手术+EODF组、脊髓损伤组和脊髓损伤+EODF组,每组9只,采用医用动脉瘤夹制备T₁₀脊髓钳夹损伤大鼠模型。于术前1 d及术后1 d、术后第2、4、6、8、10、12周对各组进行BBB评分,术后第12周进行甲苯胺蓝染色。另取180只Sprague-Dawley大鼠,分组同前,每组45只,各组又分为6 h、12 h、1 d、3 d、7 d五个时间点,每个时间点各9只。采用酶联免疫吸附试验检测血清肿瘤坏死因子-α (TNF-α)和白细胞介素-10 (IL-10)水平。结果脊髓损伤组和脊髓损伤+EODF组BBB评分在术后1 d降至最低(P<0.05),随时间逐渐增加,术后第8、10、12周,脊髓损伤+EODF组优于脊髓损伤组(P<0.05)。术后第12周,脊髓损伤+EODF组较脊髓损伤组脊髓损伤病变程度轻。与假手术组相比,脊髓损伤组术后12 h开始血清TNF-α水平升高(P<0.05),呈先升后降趋势,7 d恢复;术后各时间点血清IL-10水平均升高(P<0.05)。术后1 d,脊髓损伤+EODF组血清TNF-α表达水平低于脊髓损伤组(P<0.05);术后各时间点,脊髓损伤+EODF组与脊髓损伤组间血清IL-10水平无显著性差异(P>0.05)。结论长期EODF可促进脊髓损伤大鼠后肢运动功能障碍的恢复,减轻脊髓损伤后的病理损害程度,对脊髓损伤急性期炎性反应有一定的抑制作用,可能是其发挥神经保护作用的基础。

关键词: 脊髓损伤, 隔日限食, 运动功能, 组织结构, 炎性反应, 大鼠

Abstract: Objective To observe the effect of every-other-day fasting (EODF) on pathology and functional recovery of rats with spinal cord clip-compression injury, and to explore the related mechanism.Methods A total of 36 Sprague-Dawley rats were randomly assigned to groups A (sham operation), B (sham operation and EODF), C (spinal cord injury) and D (spinal cord injury and EODF) with nine rats in each group. The spinal cord injury rat model in T₁₀ was established by using medical aneurysm clip in latter two groups. The motor function was assessed by Basso-Beattie-Bresnahan (BBB) score one day before and one day, two, four, six, eight, ten, twelve weeks after operation; and toluidine blue staining was performed for pathological observation at twelve weeks after operation. Another 180 Sprague-Dawley rats were randomly assigned in same way. The level of tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) were detected with ELISA six hours, twelve hours, one day, three days and seven days after operation.Results The BBB score reached lowest on the first day in groups C and D (P<0.05), and gradually increased with time, and were higher in group D than in group C eight weeks, ten weeks and twelve weeks after operation (P<0.05). The pathology in spinal cord was less in group D than in group C. Compared with group A, the level of serum TNF-α increased twelve hours after operation (P<0.05), peaked one day after operation, and returned back seven days after operation; the level of serum IL-10 increased at each time point after operation (P<0.05). Compared with group C, the level of serum TNF-α was lower in group D one day after operation (P<0.05); the level of serum IL-10 was not significantly different at each time point after operation (P>0.05).Conclusion Long-term EODF can promote the hind limb motor recovery in rats with spinal cord clip-compression injury, and alleviate pathological damage. EODF might inhibit acute inflammatory reaction at acute stage of spinal cord injury, which may be correlated with its neuroprotective effect.

Key words: spinal cord injury, every-other-day fasting, motor function, tissue structure, inflammatory response, rats

中图分类号:

R651.2

何宇, 张安仁, 孙年怡, 王文春, 王志强, 田丽君, 邹文晨, 张志强. 隔日限食疗法对脊髓损伤大鼠的保护作用及其机制[J]. 《中国康复理论与实践》, 2018, 24(2): 153-159.

HE Yu, ZHANG An-ren, SUN Nian-yi, WANG Wen-chun, WANG Zhi-qiang, TIAN Li-jun, ZOU Wen-chen, ZHANG Zhi-qiang. Protective Effect and Mechanism of Every-other-day Fasting on Rats with Spinal Cord Injury[J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2018, 24(2): 153-159.

参考文献

[1] Lee BB, Cripps RA, Fitzharris M, et al.The global map for traumatic spinal cord injury epidemiology: update 2011, global incidence rate[J]. Spinal Cord, 2014, 52(2): 110-116.
[2] 吴周睿,朱元贵,程黎明,等. 脊髓损伤与修复的关键科学问题——第81期“双清论坛”综述[J]. 中国科学基金, 2013, 27(3): 147-153.
[3] Ramer LM, Ramer MS, Bradbury EJ.Restoring function after spinal cord injury: towards clinical translation of experimental strategies[J]. Lancet Neurol, 2014, 13(12): 1241-1256.
[4] Varady KA, Hellerstein MK.Alternate-day fasting and chronic disease prevention: a review of human and animal trials[J]. Am J Clin Nutr, 2007, 86(1): 7-13.
[5] Mattson MP.Energy intake and exercise as determinants of brain health and vulnerability to injury and disease[J]. Cell Metab, 2012, 16(6): 706-722.
[6] Davis LM, Pauly JR, Readnower RD, et al.Fasting is neuroprotective following traumatic brain injury[J]. J Neurosci Res, 2008, 86(8): 1812-1822.
[7] Fann DY, Santro T, Manzanero S, et al.Intermittent fasting attenuates inflammasome activity in ischemic stroke[J]. Exp Neurol, 2014, 257: 114-119.
[8] Manzanero S, Erion JR, Santro T, et al.Intermittent fasting attenuates increases in neurogenesis after ischemia and reperfusion and improves recovery[J]. J Cereb Blood Flow Metab, 2014, 34(5): 897-905.
[9] Arumugam TV, Phillips TM, Cheng A, et al.Age and energy intake interact to modify cell stress pathways and stroke outcome[J]. Ann Neurol, 2010, 67(1): 41-52.
[10] Varendi K, Airavaara M, Anttila J, et al.Short-term preoperative dietary restriction is neuroprotective in a rat focal stroke model[J]. PLoS One, 2014, 9(4): e93911.
[11] Rivlin AS, Tator CH.Effect of duration of acute spinal cord compression in a new acute cord injury model in the rat[J]. Surg Neurol, 1978, 10(1): 38-43.
[12] von Euler M, Seiger A, Sundström E. Clip compression injury in the spinal cord: a correlative study of neurological and morphological alterations[J]. Exp Neurol, 1997, 145(1): 502-510.
[13] 刘小康,徐建广,连小峰,等. 大鼠钳夹式急性脊髓损伤模型的制备与评价[J]. 中国矫形外科杂志, 2012, 20(14): 1318-1322.
[14] 李经辉,黄辉,吴海鹰,等. 钳夹型急性大鼠脊髓损伤模型的建立与评价[J]. 昆明理工大学学报(自然科学版), 2012, 37(6): 67-71, 75.
[15] Bsso 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.
[16] Dumont RJ, Okonkwo DO, Verma S, et al.Acute spinal cord injury, part I: pathophysiologic mechanisms[J]. Clin Neuropharmacol, 2001, 24(5): 254-264.
[17] Norenberg MD, Smith J, Marcillo A.The pathology of human spinal cord injury: defining the problems[J]. J Neurotrauma, 2004, 21(4): 429-440.
[18] Stammers AT, Liu J, Kwon BK.Expression of inflammatory cytokines following acute spinal cord injury in a rodent model[J]. J Neurosci Res, 2012, 90(4): 782-790.
[19] Carlson GD, Gorden C.Current developments in spinal cord injury research[J]. Spine J, 2002, 2(2):116-128.
[20] 席悦. 利用微阵列芯片技术探究脊髓损伤的分子机制[J]. 中国组织工程研究, 2013, 17(24): 4529-4538.
[21] Choo AM, Liu J, Lam CK, et al.Contusion, dislocation, and distraction: Primary hemorrhage and membrane permeability in distinct mechanisms of spinal cord injury[J]. J Neurosurg Spine, 2007, 6(3): 255-266.
[22] Mautes AE, Weinzierl MR, Donovan F, et al.Vascular events after spinal cord injury: Contributionto secondary pathogenesis[J]. Phys Ther, 2000, 80(7): 673-687.
[23] Mortazavi MM, Verma K, Harmon OA, et al.The microanatomy of spinal cord injury: a review[J]. Clin Anat, 2015, 28(1): 27-36.
[24] Jeong MA, Plunet W, Streijger F, et al.Intermittent fasting improves functional recovery after rat thoracic contusion spinal cord injury[J]. J Neurotrauma, 2011, 28(3): 479-492.
[25] 刘捷. 饮食干预疗法对急性脊髓损伤治疗作用的研究[J]. 中国骨科临床与基础研究杂志, 2012, 4(1): 75.
[26] Plunet WT, Streijger F, Lam CK, et al.Dietary restriction started after spinal cord injury improves functional recovery[J]. Exp Neurol, 2008, 213(1): 28-35.
[27] Plunet WT, Lam CK, Lee JH, et al. Prophylactic dietary restriction may promote functional recovery and increase lifespan after spinal cord injury [J]. Ann NY Acad Sci, 2010, 1198 Suppl 1: E1-E11.
[28] Moghaddam A, Child C, Bruckner T, et al.Posttraumatic inflammation as a key to neuroregeneration after traumatic spinal cord injury[J]. Int J Mol Sci, 2015, 16(4): 7900-7916.
[29] Yang L, Jones NR, Blumbergs PC, et al.Severity-dependent expression of pro-inflammatory cytokines in traumatic spinal cord injury in the rat[J]. J Clin Neurosci, 2005, 12(3): 276-284.
[30] Kwon BK, Stammers AM, Belanger LM, et al.Cerebrospinal fluid inflammatory cytokines and biomarkers of injury severity in acute human spinal cord injury[J]. J Neurotrauma, 2010, 27(4): 669-682.
[31] Taylor AR, Welsh CJ, Young C, et al.Cerebrospinal fluid inflammatory cytokines and chemokines in naturally occurring canine spinal cord injury[J]. J Neurotrauma, 2014, 31(18): 1561-1569.
[32] Urdzíková LM, Rùžièka J, LaBagnara M, et al. Human mesenchymal stem cells modulate inflammatory cytokines after spinal cord injury in rat[J]. Int J Mol Sci, 2014, 15(7): 11275-11293.
[33] Ishii H, Tanabe S, Ueno M, et al.IFN-γ-dependent secretion of IL-10 from Th1 cells and microglia/macrophages contributes to functional recovery after spinal cord injury[J]. Cell Death Dis, 2013, 4: e710.
[34] Knoblach SM, Faden AI.Interleukin-10 improves outcome and alters proinflammatory cytokine expression after experimental traumatic brain injury[J]. Exp Neurol, 1998, 153(1): 143-151.
[35] Bethea JR, Nagashima H, Acosta MC, et al.Systemically administered interleukin-10 reduces tumor necrosis factor-alpha production and significantly improves functional recovery following traumatic spinal cord injury in rats[J]. J Neurotrauma, 1999, 16(10): 851-863.
[36] Genovese T, Esposito E, Mazzon E, et al.Absence of endogenous interleukin-10 enhances secondary inflammatory process after spinal cord compression injury in mice[J]. J Neurochem, 2009, 108(6): 1360-1372.
[37] Nakamura M, Houghtling RA, Macarthur L, et al.Differences in cytokine gene expression profile between acute and secondary injury in adult rat spinal cord[J]. Exp Neurol, 2003, 184(1): 313-325.
[38] Bethea JR, Dietrich WD.Targeting the host inflammatory response in traumatic spinal cord injury[J]. Curr Opin Neurol, 2002, 15(3): 355-360.

隔日限食疗法对脊髓损伤大鼠的保护作用及其机制

Protective Effect and Mechanism of Every-other-day Fasting on Rats with Spinal Cord Injury

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

Metrics

本文评价

推荐阅读 0

[1]	陈珺雯, 陈谦, 陈程, 李淑月, 刘玲玲, 吴存书, 龚翔, 鲁俊, 许光旭. 改良八段锦身体活动对脑卒中患者心肺功能、运动功能和日常生活活动能力的效果[J]. 《中国康复理论与实践》, 2024, 30(1): 74-80.
[2]	刘冬, 徐子涵, 李江, 鞠萍. M1区联合背外侧前额叶高频重复经颅磁刺激对脊髓损伤后神经病理性疼痛患者脑电图θ振幅的效果[J]. 《中国康复理论与实践》, 2024, 30(1): 87-94.
[3]	孙藤方, 任梦婷, 杨琳, 王耀霆, 王红雨, 闫兴洲. 高压氧治疗联合重复外周磁刺激干预脑卒中患者踝运动功能和平衡能力的效果[J]. 《中国康复理论与实践》, 2023, 29(8): 875-881.
[4]	王亚楠, 刘西花. 脑卒中偏瘫患者主观和客观平衡功能测量的相关性及预测效能[J]. 《中国康复理论与实践》, 2023, 29(8): 890-895.
[5]	王海云, 王寅, 周信杰, 何爱群. 基于“中枢-外周-中枢”理论的经颅直流电刺激结合针刺干预脑卒中患者中枢及上肢功能的效果[J]. 《中国康复理论与实践》, 2023, 29(8): 919-925.
[6]	陈怡婷, 王倩, 崔慎红, 李映彩, 张思鈺, 魏衍旭, 任慧, 冷军, 陈斌. 双侧序贯重复经颅磁刺激干预脑卒中患者上肢运动功能的效果[J]. 《中国康复理论与实践》, 2023, 29(8): 926-932.
[7]	李芳, 霍速, 杜巨豹, 刘秀贞, 李小爽, 宋为群. 经颅直流电刺激联合任务导向性康复训练对脊髓损伤大鼠前肢运动障碍的效果[J]. 《中国康复理论与实践》, 2023, 29(7): 777-781.
[8]	崔尧, 丛芳, 黄富表, 曾明, 颜如秀. 不同镜像神经元训练策略下脑与肌肉的活动特征：基于近红外光谱与表面肌电图技术[J]. 《中国康复理论与实践》, 2023, 29(7): 782-790.
[9]	刘宁, 刘雨泉, 祝斌, 于凌佳, 谭海宁, 杨雍, 李想. 脊髓损伤神经学分类国际标准国内应用情况的文献计量学研究[J]. 《中国康复理论与实践》, 2023, 29(7): 808-815.
[10]	刘辉, 尹航, 贾绍辉, 邱服冰. 适用于残疾儿童青少年运动功能和运动能力测量工具的结构、内容和心理测量特性的系统综述[J]. 《中国康复理论与实践》, 2023, 29(6): 630-638.
[11]	王一吉, 周红俊, 何泽佳, 刘根林, 郑樱, 郝春霞, 卫波, 康海琼, 张缨, 逯晓蕾, 袁媛, 蒙倩茹. 不完全性脊髓损伤患者运动功能对称性与步态对称性的关系[J]. 《中国康复理论与实践》, 2023, 29(6): 639-645.
[12]	许苗苗, 李楠, 应颖, 杨凯翔, 杨婧瑞, 李杰, 邱彦群. 重复外周磁刺激对左右颈7神经交叉移位术后脑卒中患者上肢运动功能的效果[J]. 《中国康复理论与实践》, 2023, 29(6): 686-690.
[13]	郑莉, 鲍治诚, 张琪, 任绪艳, 苏敏. 经皮耳迷走神经电刺激结合康复机器人训练对脑卒中患者上肢功能的效果[J]. 《中国康复理论与实践》, 2023, 29(6): 691-696.
[14]	张倩, 孙新亭. 视频镜像训练对脑卒中恢复期患者下肢功能的效果[J]. 《中国康复理论与实践》, 2023, 29(6): 703-707.
[15]	林煜凡, 韦添元, 张晓颖, 李晁金子, 何静杰, 杜晓霞. 音乐治疗对脑卒中后认知障碍的效果[J]. 《中国康复理论与实践》, 2023, 29(6): 714-719.