Objective To observe the effects of ginsenoside Rb1 pretreatment on spinal cord ischemia-reperfusion injury in rats, and to explore the possible mitochondrial mechanism of ginsenoside Rb1 against ischemia-reperfusion injury. Methods The spinal cord ischemia-reperfusion injury model was established. The rats were randomly divided into sham operation group (n=12), ischemia-reperfusion group (n=12) and drug group (n=12). The drug group received ginsenoside Rb1 peritoneal injection with 10 mg/kg, 20 mg/kg, 40 mg/kg and 80 mg/kg, respectively, 30 minutes before modeling and once a day after modeling. After 48 hours of reperfusion, the BBB score was tested, the levels of superoxide dismutase (SOD) and malonaldehyde (MDA) in the serum and spinal cord tissue, and the cytochrome C oxidase (COX) activity in spinal cord tissue were detected.Results Compared with the ischemia-reperfusion group, the BBB score increased (P<0.05), the SOD level increased, and the MDA level decreased both in serum and spinal cord tissue, the activity of COX increased in the spinal cord tissue (P<0.05). All the indexes were dose-dependent, however, no difference was found between 40 mg/kg and 80 mg/kg.Conclusion Ginsenoside Rb1 can inhibit oxidative stress induced by spinal cord ischemia-reperfusion injury in rats by inhibiting mitochondrial damage. The protective effect of ginsenoside Rb1 on the spinal cord ischemia-reperfusion injury is dose-dependent during 10 to 40 mg/kg dose.
CHENG Bin
,
YANG Feng
,
LI Feng-tao
,
LIN Lei
,
XUE Jian-li
,
WU Hao
,
YE Jin-tao
. Protective Effect of Ginsenoside Rb1 on Spinal Cord Ischemic-reperfusion Injury in Rats by Alleviating Mitochondrial Damage[J]. Chinese Journal of Rehabilitation Theory and Practice, 2018
, 24(6)
: 629
-633
.
DOI: 10.3969/j.issn.1006-9771.2018.06.002
[1] Crawford ES, Rubio PA.Reappraisal of adjuncts to avoid ischemia in the treatment of aneurysms of descending thoracic aorta[J]. J Thorac Cardiovasc Surg, 1973, 66(5): 693-704.
[2] Wynn MM, Acher CW.A modern theory of spinal cord ischemia/injury in thoracoabdominal aortic surgery and its implications for prevention of paralysis[J]. J Cardiothorac Vasc Anesth, 2014, 28(4): 1088-1099.
[3] 夏炳江,肖鲁伟. 脊髓慢性压迫减压后缺血再灌注损伤研究进展[J]. 中华中医药学刊, 2017, 35(4): 998-1001.
[4] 王国丽,李晓娇,张力娜,等. 人参皂苷Rb1、Rg1对中枢神经系统作用及相关机制的研究进展[J]. 上海中医药杂志, 2017, 51(3): 92-95.
[5] 林少滨. 人参皂苷Rb1后处理对大鼠全脑缺血再灌注后认知功能的影响[J]. 海峡药学, 2017, 29(7):15-17.
[6] Murphy AN, Fiskum G, Beal MF.Mitochondria in neurodegeneration: bioenergetic function in cell life and death[J]. J Cereb Blood Flow Metab, 1999, 19(3): 231-245.
[7] D'Herde K, De Prest B, Mussche S, et al. Ultrastructural localization of cytochrome C in apoptosis demonstrates mitochondrial heterogeneity[J]. Cell Death Differ, 2000, 7(4): 331-337.
[8] Cao XH, Zhao SS, Liu DY, et al.ROS-Ca(2+) is associated with mitochondria permeability transition pore involved in surfactin-induced MCF-7 cells apoptosis[J]. Chem Biol Interact, 2011, 190(1): 16-27.
[9] Wang Y, Jiang YF, Huang QF, et al.Neuroprotective effects of salvianolic acid B against oxygen-glucose deprivation/reperfusion damage in primary rat cortical neurons[J]. Chin Med J (Engl), 2010, 123(24): 3612-3619.
[10] Ye R, Zhang X, Kong X, et al.Ginsenoside Rd attenuates mitochondrial dysfunction and sequential apoptosis after transient focal ischemia[J]. Neuroscience, 2011, 178(3): 169.
[11] Toescu EC, Gardner JM, Petersen OH.Mitochondrial Ca<sup>2+</sup> uptake at submicromolar [Ca<sup>2+</sup>]i in permeabilised pancreatic acinar cells[J]. Biochem Biophys Res Commun, 1993, 192(2): 854-859.
[12] Schild L, Huppelsberg J, Kahlert S, et al.Brain mitochondria are primed by moderate Ca<sup>2+</sup> rise upon hypoxia/reoxygenation for functional breakdown and morphological disintegration[J]. J Biol Chem, 2003, 278(28): 25454-25460.
[13] Frantseva MV, Carlen PL, Perez Velazquez JL.Dynamics of intracellular calcium and free radical production during ischemia in pyramidal neurons[J]. Free Radical Biology & Medicine, 2001, 31(10): 1216-1227.
[14] Zhao Q, Zhang C, Wang X, et al.(S)-ZJM-289, a nitric oxide-releasing derivative of 3-N-butylphthalide, protects against ischemic neuronal injury by attenuating mitochondrial dysfunction and associated cell death[J]. Neurochem Int, 2012, 60(2): 134-144.
[15] Zhang H, Li Q, Li Z, et al.The protection of Bcl-2 overexpression on rat cortical neuronal injury caused by analogous ischemia/reperfusion in vitro[J]. Neurosci Res, 2008, 62(2): 140-146.
[16] 余智,于民,顾苏兵,等. [Gly14]-Humanin对局灶性脑缺血再灌注损伤大鼠氧化应激及神经细胞凋亡的影响[J]. 预防医学, 2018, 30(1): 55-58.
[17] 李春雷,黄川锋,张峰. 醒脑静注射液联合醒脑窍法对脑缺血再灌注大鼠血清及脑组织炎症因子水平的影响[J]. 中国临床药理学杂志, 2016, 32(20): 1873-1877.
[18] Nanetti L, Taffi R, Vignini A, et al.Reactive oxygen species plasmatic levels in ischemic stroke[J]. Mol Cell Biochem, 2007, 303(1-2): 19-25.
[19] Galpern WR, Cudkowicz ME.Coenzyme Q treatment of neurodegenerative diseases of aging[J]. Mitochondrion, 2007, 7(Suppl): S146-S153.
[20] Udipi K, Ornberg RL, Thurmond KN, et al.Modification of inflammatory response to implanted biomedical materials in vivo by surface bound superoxide dismutase mimics[J]. J Biomed Mater Res, 2000, 51(4): 549-560.
[21] 孔令恒,陈玉龙,孙娜,等. 抑制CaMKII减轻线粒体氧化应激可改善离体心脏缺血再灌注损伤[J]. 南方医科大学学报, 2018, 38(2): 181-186.
[22] 方华,李华凤,张伟晶,等. 腹主动脉灌注瑞芬太尼聚己内酯减轻脊髓缺血再灌注损伤的实验研究[J]. 生物医学工程学杂志, 2016, 33(4): 735-740.
[23] Vogt S, Troitzsch D, Abdul-Khaliq H, et al.Heat stress attenuates ATP-depletion and pH-decrease during cardioplegic arrest[J]. J Surg Res, 2007, 139(2): 176-181.
[24] Lee I, Salomon AR, Ficarro S, et al.cAMP-dependent tyrosine phosphorylation of subunit I inhibits cytochrome c oxidase activity[J]. J Biol Chem, 2005, 280(7): 6094-6100.
[25] Yu Q, Nguyen T, Ogbi M, et al.Differential loss of cytochrome-C oxidase subunits in ischemia-reperfusion injury: exacerbation of COI subunit loss by PKC-epsilon inhibition[J]. Am J Physiol Heart Circ Physiol, 2008, 294(6): H2637-H2645.
[26] 杨柳,许舜军,曾星,等. 人参皂苷Rb_1在大鼠体内的药物代谢研究[J]. 高等学校化学学报, 2006, 27(6): 1042-1044.
[27] 胡锦芳,温金华,蒋丽华. 复方血栓通片中人参皂苷Rb1与Rg1在大鼠体内的药代动力学研究[J]. 南昌大学学报(医学版), 2011, 51(11): 6-9.