不同剂量人参皂甙Rb1对大鼠脊髓缺血再灌注损伤及survivin的作用
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摘要
目的观察不同剂量人参皂甙Rb1预处理对于大鼠脊髓缺血再灌注后的干预效果,并探讨其可能机制。方法 Sprague-Dawley大鼠随机分为假手术组,模型组以及药物10 mg/kg(D10)、20 mg/kg(D20)、40 mg/kg(D40)、80 mg/kg(D80)组,每组12只。药物组于造模前30 min腹腔注射相应剂量人参皂甙Rb1。构建大鼠脊髓缺血10 min再灌注模型。造模后48 h行BBB评分,HE染色及TUNEL检测观察细胞凋亡,免疫组化法观察survivin蛋白表达。结果各药物组BBB评分均高于模型组(P<0.05),以D40和D80组最高;survivin蛋白表达均高于模型组(P<0.05),以D40和D80组最高;神经细胞凋亡少于模型组(P<0.05),以D40和D80组最少。结论人参皂甙Rb1可以通过促进survivin的表达,抑制大鼠脊髓缺血再灌注造成的细胞凋亡,保护神经功能;在一定范围内,人参皂甙Rb1对脊髓缺血再灌注损伤的保护作用具有剂量依赖性。
Objective To observe the effects of different dosages of ginsenoside Rb1 preconditioning on spinal cord ischemia-reperfusion injury in rats, and the possible mechanism.Methods Sprague-Dawley rats were randomly divided into sham group(n=12), model group(n=12), and 10 mg/kg(D10, n=12), 20 mg/kg(D20, n=12), 40 mg/kg(D40, n=12) and 80 mg/kg(D80, n=12) drug groups. Spinal cord ischemia for ten minutes and reperfusion model was established, and the drug groups were injected ginsenoside Rb1 intraperitoneally in their dosages 30 minutes before modeling. They were assessed with BBB score 48 hours after reperfusion, and then were sacrificed for HE staining, TUNEL staining and immunohistochemistry staining of survivin.Results The BBB score was more in the drug groups than in the model group(P<0.05), and was the most in D40 and D80 groups. The expression of survivin was more in the drug groups than in the model group(P<0.05), and was the most in D40 and D80 groups. The apoptosis of neurons was less in the drug groups than in the model group(P<0.05), and was the least in D40 and D80 groups.Conclusion The ginsenoside Rb1 could promote the expression of survivin, inhibit apoptosis of neurons, to protect the neural function, in dose-dependent manner somehow.
Objective To observe the effects of different dosages of ginsenoside Rb1 preconditioning on spinal cord ischemia-reperfusion injury in rats, and the possible mechanism.Methods Sprague-Dawley rats were randomly divided into sham group(n=12), model group(n=12), and 10 mg/kg(D10, n=12), 20 mg/kg(D20, n=12), 40 mg/kg(D40, n=12) and 80 mg/kg(D80, n=12) drug groups. Spinal cord ischemia for ten minutes and reperfusion model was established, and the drug groups were injected ginsenoside Rb1 intraperitoneally in their dosages 30 minutes before modeling. They were assessed with BBB score 48 hours after reperfusion, and then were sacrificed for HE staining, TUNEL staining and immunohistochemistry staining of survivin.Results The BBB score was more in the drug groups than in the model group(P<0.05), and was the most in D40 and D80 groups. The expression of survivin was more in the drug groups than in the model group(P<0.05), and was the most in D40 and D80 groups. The apoptosis of neurons was less in the drug groups than in the model group(P<0.05), and was the least in D40 and D80 groups.Conclusion The ginsenoside Rb1 could promote the expression of survivin, inhibit apoptosis of neurons, to protect the neural function, in dose-dependent manner somehow.
引文
[1]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.
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[7]Zumbragel FK,Machtens DA,Curth U,et al.Survivin does not influence the anti-apoptotic action of XIAP on caspase-9[J].Biochem Biophys Res Commun,2017,482(4):530-535.
[8]Ceballoscancino G,Espinosa M,Maldonado V,et al.Regulation of mitochondrial Smac/DIABLO-selective release by survivin[J].Oncogene,2007,26(54):7569-7575.
[9]孙延卿,陈雄生,曹东,等.氢盐水可抑制脊髓缺血再灌注损伤兔模型运动神经元的凋亡[J].中国组织工程研究,2014,18(18):2861-2866.
[10]Seo JY,Lee JH,Kim NW,et al.Effect of a fermented ginseng extract,BST204,on the expression of cyclooxygenase-2 in murine macrophages[J].Int Immunopharmacol,2005,5(5):929-936.
[11]Wang W,Rayburn EM,Zhao Y,et al.Experimental therapy of prostate cancer with novel natural product anti-cancer ginsenosides[J].Prostate,2010,68(8):809-819.
[12]Dong X,Zheng L,Lu S,et al.Neuroprotective effects of pretreatment of ginsenoside Rb1 on severe cerebral ischemia-induced injuries in aged mice:involvement of anti-oxidant signaling[J].Geriatr Gerontol Int,2017,17(2):338-345.
[13]Park S,Ahn IS,Kwon DY,et al.Ginsenosides Rb1 and Rg1suppress triglyceride accumulation in 3T3-L1 adipocytes and enhance beta-cell insulin secretion and viability in Min6 cells via PKA-dependent pathways[J].Biosci Biotechnol Biochem,2008,72(11):2815-2823.
[14]Leung KW,Leung FP,Huang Y,et al.Non-genomic effects of ginsenoside-Re in endothelial cells via glucocorticoid receptor[J].Febs Letters,2007,581(13):2423-2428.
[15]Yu S,Zhou X,Li F,et al.Microbial transformation of ginsenoside Rb1,Re and Rg1 and its contribution to the improved anti-inflammatory activity of ginseng[J].Sci Rep,2017,7(1):138.
[16]Chang Y,Huang WJ,Tien LT,et al.Ginsenosides Rg1 and Rb1 enhance glutamate release through activation of protein kinase A in rat cerebrocortical nerve terminals(synaptosomes)[J].Eur J Pharmacol,2008,578(1):28-36.
[17]Cui YC,Pan CS,Yan L,et al.Ginsenoside Rb1 protects against ischemia/reperfusion-induced myocardial injury via energy metabolism regulation mediated by Rho A signaling pathway[J].Sci Rep,2017,7:44579.
[18]Fujita K,Hakuba N,Hata R,et al.Ginsenoside Rb1 protects against damage to the spiral ganglion cells after cochlear ischemia[J].Neurosci Lett,2007,415(2):113-117.
[19]Sakanaka M,Zhu P,Zhang B,et al.Intravenous infusion of dihydroginsenoside Rb1 prevents compressive spinal cord injury and ischemic brain damage through upregulation of VEGF and Bcl-XL[J].J Neurotrauma,2007,24(6):1037-1054.
[20]Zhang G,Liu A,Zhou Y,et al.Panax ginseng ginsenoside-Rg2 protects memory impairment via anti-apoptosis in a rat model with vascular dementia[J].J Ethnopharmacol,2008,115(3):441-448.
[21]Yang H,Oh KH,Kim HJ,et al.Ginsenoside-Rb2 and 20(S)-Ginsenoside-Rg3 from Korean Red Ginseng Prevent Rotavirus Infection in Newborn Mice[J].J Microbiol Biotechnol,2018,28(3):391-396.
[22]Huang Q,Wang T,Yang L,et al.Ginsenoside Rb2 alleviates hepatic lipid accumulation by restoring autophagy via induction of Sirt1 and activation of AMPK[J].Int J Mol Sci,2017,18(5):E1063.
[2]Rezaian J.Role of apoptosis in CNS emphasizing spinal cord injuries:a commentary[J].Iranian J Neurol,2016,1(4):30-31.
[3]Kumar S.Caspase function in programmed cell death[J].Cell Death Differ,2007,14(1):32-43.
[4]Sokolowska J,Urbanska K.Survivin expression in correlation with apoptotic activity in canine lymphomas[J].Pol J Vet Sci,2017,20(2):329-338.
[5]Zheng Q,Bao XY,Zhu PC,et al.Ginsenoside Rb1 for myocardial ischemia/reperfusion injury:preclinical evidence and possible mechanisms[J].Oxid Med Cell Longev,2017,2017:6313625.
[6]张辉,董建锋,赵秋振,等.川芎嗪对脑缺血再灌注皮质神经元生存素表达的影响[J].中国组织化学与细胞化学杂志,2007,16(6):682-685.
[7]Zumbragel FK,Machtens DA,Curth U,et al.Survivin does not influence the anti-apoptotic action of XIAP on caspase-9[J].Biochem Biophys Res Commun,2017,482(4):530-535.
[8]Ceballoscancino G,Espinosa M,Maldonado V,et al.Regulation of mitochondrial Smac/DIABLO-selective release by survivin[J].Oncogene,2007,26(54):7569-7575.
[9]孙延卿,陈雄生,曹东,等.氢盐水可抑制脊髓缺血再灌注损伤兔模型运动神经元的凋亡[J].中国组织工程研究,2014,18(18):2861-2866.
[10]Seo JY,Lee JH,Kim NW,et al.Effect of a fermented ginseng extract,BST204,on the expression of cyclooxygenase-2 in murine macrophages[J].Int Immunopharmacol,2005,5(5):929-936.
[11]Wang W,Rayburn EM,Zhao Y,et al.Experimental therapy of prostate cancer with novel natural product anti-cancer ginsenosides[J].Prostate,2010,68(8):809-819.
[12]Dong X,Zheng L,Lu S,et al.Neuroprotective effects of pretreatment of ginsenoside Rb1 on severe cerebral ischemia-induced injuries in aged mice:involvement of anti-oxidant signaling[J].Geriatr Gerontol Int,2017,17(2):338-345.
[13]Park S,Ahn IS,Kwon DY,et al.Ginsenosides Rb1 and Rg1suppress triglyceride accumulation in 3T3-L1 adipocytes and enhance beta-cell insulin secretion and viability in Min6 cells via PKA-dependent pathways[J].Biosci Biotechnol Biochem,2008,72(11):2815-2823.
[14]Leung KW,Leung FP,Huang Y,et al.Non-genomic effects of ginsenoside-Re in endothelial cells via glucocorticoid receptor[J].Febs Letters,2007,581(13):2423-2428.
[15]Yu S,Zhou X,Li F,et al.Microbial transformation of ginsenoside Rb1,Re and Rg1 and its contribution to the improved anti-inflammatory activity of ginseng[J].Sci Rep,2017,7(1):138.
[16]Chang Y,Huang WJ,Tien LT,et al.Ginsenosides Rg1 and Rb1 enhance glutamate release through activation of protein kinase A in rat cerebrocortical nerve terminals(synaptosomes)[J].Eur J Pharmacol,2008,578(1):28-36.
[17]Cui YC,Pan CS,Yan L,et al.Ginsenoside Rb1 protects against ischemia/reperfusion-induced myocardial injury via energy metabolism regulation mediated by Rho A signaling pathway[J].Sci Rep,2017,7:44579.
[18]Fujita K,Hakuba N,Hata R,et al.Ginsenoside Rb1 protects against damage to the spiral ganglion cells after cochlear ischemia[J].Neurosci Lett,2007,415(2):113-117.
[19]Sakanaka M,Zhu P,Zhang B,et al.Intravenous infusion of dihydroginsenoside Rb1 prevents compressive spinal cord injury and ischemic brain damage through upregulation of VEGF and Bcl-XL[J].J Neurotrauma,2007,24(6):1037-1054.
[20]Zhang G,Liu A,Zhou Y,et al.Panax ginseng ginsenoside-Rg2 protects memory impairment via anti-apoptosis in a rat model with vascular dementia[J].J Ethnopharmacol,2008,115(3):441-448.
[21]Yang H,Oh KH,Kim HJ,et al.Ginsenoside-Rb2 and 20(S)-Ginsenoside-Rg3 from Korean Red Ginseng Prevent Rotavirus Infection in Newborn Mice[J].J Microbiol Biotechnol,2018,28(3):391-396.
[22]Huang Q,Wang T,Yang L,et al.Ginsenoside Rb2 alleviates hepatic lipid accumulation by restoring autophagy via induction of Sirt1 and activation of AMPK[J].Int J Mol Sci,2017,18(5):E1063.