术后24 h给予莫诺苷对局灶性脑缺血再灌注大鼠保护作用的研究
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摘要
目的研究莫诺苷对大鼠局灶性脑缺血再灌注后24 h给药对血管新生相关因子及神经功能的影响。方法健康成年雄性SD大鼠,用线栓法制备大鼠局灶性脑缺血再灌注模型,术后随机分为假手术组,模型组,莫诺苷小(30 mg/kg)、中(90 mg/kg)、大(270 mg/kg)剂量组,术后24 h开始给予莫诺苷,每天灌胃1次,连续给药7 d。通过检测神经功能行为学评分,脑梗死体积百分比,皮层血管新生相关蛋白的表达,研究大鼠局灶性脑缺血再灌注后24 h给予莫诺苷对血管新生相关蛋白及神经功能恢复的影响。结果与假手术组相比,模型组神经功能评分和脑梗死体积百分比显著增加(P<0. 001),给药7 d后,莫诺苷大剂量组与模型组相比,明显降低了神经功能评分(P<0. 01),且能显著降低脑梗死体积(P<0. 05)。与假手术相比,皮层血管新生相关蛋白CD34和Ang-1的表达均增加(P<0. 05,P<0. 05)。与模型组相比,莫诺苷大剂量组皮层血管新生相关蛋白CD34和Ang-1的表达显著增加(P<0. 05,P<0. 01),其中莫诺苷中剂量组也能促进Ang-1的表达(P<0. 05)。结论莫诺苷给药时间窗扩大至局灶性脑缺血再灌注后24 h,其大剂量组可以降低神经功能评分,减小脑梗死体积,对CD34及Ang-1血管新生相关蛋白有调节作用。
Objective To investigate the effects of morroniside on angiogenesis-related factors and neurological function in rats 24 h after focal cerebral ischemia-reperfusion. Methods Healthy adult male SD rats were induced to develop occlusion of the middle cerebral artery by suture embolus. Then,the rats were randomly divided into a sham group,a model group,a morroniside-low group,a morroniside-intermediate group,and a morroniside low,moderate,and high-dose groups( 30,90,and 270 mg/kg,respectively). Morroniside was administered 24 h after surgery,once a day for 7 days.By determining the scores of neurological behavior,the cerebral infarction volume ratios,and the expression of cortical angiogenesis-related gene proteins,were investigated to explore the effects of morroniside on angiogenesis-related proteins and neurological function in rats at 24 h after focal cerebral ischemia-reperfusion. Results Compared with those in the sham group,the scores of neurological behavior and the cerebral infarction volume ratios in the model group were significantly increased( P<0. 001). After 7 days of morroniside administration,compared with that in the model group,the morroniside-high dose group exhibited a dramatic improvement of the neurological behavior scores( P < 0. 01) and a significant reduction in the volume of cerebral infarction( P < 0. 05). Moreover,the expression of cortical angiogenesisrelated proteins CD34 and Ang-1 were significantly increased( P<0. 05,P<0. 05) compared with those in the sham group.Compared with the model group,the expression of cortical angiogenesis-related proteins CD34 and Ang-1 in the group with high-dose morroniside was significantly increased( P < 0. 05,P < 0. 01),and moderate-dose morroniside also promoted the expression of Ang-1( P< 0. 05). Conclusions The time window for morroniside administration extends to 24 h after focal cerebral ischemia-reperfusion. The morroniside administration at a high dose can reduce the neurological behavior scores and the cerebral infarction volume ratio,while increasing the expression of the angiogenesis-related proteins CD34 and Ang-1.
Objective To investigate the effects of morroniside on angiogenesis-related factors and neurological function in rats 24 h after focal cerebral ischemia-reperfusion. Methods Healthy adult male SD rats were induced to develop occlusion of the middle cerebral artery by suture embolus. Then,the rats were randomly divided into a sham group,a model group,a morroniside-low group,a morroniside-intermediate group,and a morroniside low,moderate,and high-dose groups( 30,90,and 270 mg/kg,respectively). Morroniside was administered 24 h after surgery,once a day for 7 days.By determining the scores of neurological behavior,the cerebral infarction volume ratios,and the expression of cortical angiogenesis-related gene proteins,were investigated to explore the effects of morroniside on angiogenesis-related proteins and neurological function in rats at 24 h after focal cerebral ischemia-reperfusion. Results Compared with those in the sham group,the scores of neurological behavior and the cerebral infarction volume ratios in the model group were significantly increased( P<0. 001). After 7 days of morroniside administration,compared with that in the model group,the morroniside-high dose group exhibited a dramatic improvement of the neurological behavior scores( P < 0. 01) and a significant reduction in the volume of cerebral infarction( P < 0. 05). Moreover,the expression of cortical angiogenesisrelated proteins CD34 and Ang-1 were significantly increased( P<0. 05,P<0. 05) compared with those in the sham group.Compared with the model group,the expression of cortical angiogenesis-related proteins CD34 and Ang-1 in the group with high-dose morroniside was significantly increased( P < 0. 05,P < 0. 01),and moderate-dose morroniside also promoted the expression of Ang-1( P< 0. 05). Conclusions The time window for morroniside administration extends to 24 h after focal cerebral ischemia-reperfusion. The morroniside administration at a high dose can reduce the neurological behavior scores and the cerebral infarction volume ratio,while increasing the expression of the angiogenesis-related proteins CD34 and Ang-1.
引文
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[5]艾厚喜,李蕾,许栋明,等.莫诺苷对局灶性脑缺血再灌注大鼠皮层总抗氧化能力影响[J].中国康复理论与实践,2009(09):833-834.
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[8] Sun FL,Wen W,Wei Z,et al. Promoting neurogenesis via Wnt/β-catenin signaling pathway accounts for the neurorestorative effects of morroniside against cerebral ischemia injury[J]. Eur J Pharmacol,2014,738:214-221.
[9]王志敏,孙芳玲,刘婷婷,等.莫诺苷对局灶性脑缺血再灌注大鼠皮层CD_(34)表达的影响[J].中国康复理论与实践,2016(01):27-31.
[10] Liu T, Xiang B, Guo D, et al. Morroniside promotes angiogenesis and further improves microvascular circulation after focal cerebral ischemia/reperfusion[J]. Brain Res Bull,2016,127:111-118.
[11]刘婷婷,孙芳玲,程华,等.莫诺苷对局灶性脑缺血再灌注大鼠血管生成素1及其受体Tie-2的影响[J].中国康复理论与实践,2015(01)9-11.
[12] Wang W,Xu J,Li L,et al. Neuroprotective effect of morroniside on focal cerebral ischemia in rats[J]. Brain Res Bull,2010,83(5):196-201.
[13]相婕,许栋明,王文,等.莫诺苷对大鼠局灶性脑缺血再灌注损伤神经功能的影响[J].中国比较医学杂志2010(01):10-14.
[14] Longa EZ,Weinstein PR,Carlson S,et al. Reversible middle cerebral artery occlusion without craniectomy in rats[J]. Stroke,1989,20(1):84-91.
[15] Bederson JB,Pitts LH,Germano SM,et al. Evaluation of 2,3,5-triphenyltetrazolium chloride as a stain for detection and quantification of experimental cerebral infarction in rats[J].Stroke,1986,17(6):1304.
[16]但毕堂,彭小祥,陈小奇,等.急性缺血性脑卒中时间窗内的动静脉溶栓分层治疗的对比研究[J].卒中与神经疾病,2014(06):334-336.
[17] Amantea D,Certo M,Russo R,et al. Early reperfusion injury is associated to MMP2 and IL-1βelevation in cortical neurons of rats subjected to middle cerebral artery occlusion[J].Neuroscience,2014,277:755.
[18] Green AR. Pharmacological approaches to acute ischaemic stroke:reperfusion certainly,neuroprotection possibly[J]. Br J Pharmacol,2008,153(S1):S325-S338.
[19] Ruan L,Wang B,Zhuge Q,et al. Coupling of neurogenesis and angiogenesis after ischemic stroke[J]. Brain Res,2015,1623:166-173.
[20] Banerjee S, Bentley P, Hamady M, et al. Intra-arterial immunoselected CD34+stem cells for acute ischemic stroke[J].Stem Cells Transl Med,2014,3(11):1322-1330.
[21] Zhan K,Bai L,Xu J. Role of vascular endothelial progenitor cells in construction of new vascular loop[J]. Microvasc Res,2013,90:1-11.
[22] Paczkowska E, Larysz B, Rzeuski R, et al. Human hematopoietic stem/progenitor-enriched CD34+cells are mobilized into peripheral blood during stress related to ischemic stroke or acute myocardial infarction[J].Eur J Haematol,2005,75(6):461-467.
[23] Olsen JJ,Pohl SO, Deshmukh A, et al. The role of wnt signalling in angiogenesis[J] Clin Biochem Rev,2017,38(3):131-142.
[24] Palmer TD,Willhoite AR,Gage FH. Vascular niche for adult hippocampal neurogenesis[J]. J Comp Neurol,2000,425(4):479-494.
[2] Kim KW. Brain angiogenesis in developmental and pathological processes[J]. FEBS J,2009,276(17):4621.
[3] Arai K,Jin G,Navaratna D,et al. Brain angiogenesis in developmental and pathological processes:neurovascular injury and angiogenic recovery after stroke[J]. FEBS J,2009,276(17):4644-4652.
[4] Beck H,Acker T,Wiessner C,et al. Expression of angiopoietin-1,angiopoietin-2,and tie receptors after middle cerebral artery occlusion in the rat[J]. Am J Pathol,2000,157(5):1473-1483.
[5]艾厚喜,李蕾,许栋明,等.莫诺苷对局灶性脑缺血再灌注大鼠皮层总抗氧化能力影响[J].中国康复理论与实践,2009(09):833-834.
[6]侯虹丽,孙芳玲,艾厚喜,等.莫诺苷对脑缺血再灌注大鼠皮层梗死周边区基质金属蛋白酶表达的影响[J].中国康复理论与实践,2015(01):5-8.
[7]王文,许栋明,相婕,等.莫诺苷对大鼠脑缺血再灌注神经凋亡的影响[J].中国康复理论与实践,2009(12):1101-1103.
[8] Sun FL,Wen W,Wei Z,et al. Promoting neurogenesis via Wnt/β-catenin signaling pathway accounts for the neurorestorative effects of morroniside against cerebral ischemia injury[J]. Eur J Pharmacol,2014,738:214-221.
[9]王志敏,孙芳玲,刘婷婷,等.莫诺苷对局灶性脑缺血再灌注大鼠皮层CD_(34)表达的影响[J].中国康复理论与实践,2016(01):27-31.
[10] Liu T, Xiang B, Guo D, et al. Morroniside promotes angiogenesis and further improves microvascular circulation after focal cerebral ischemia/reperfusion[J]. Brain Res Bull,2016,127:111-118.
[11]刘婷婷,孙芳玲,程华,等.莫诺苷对局灶性脑缺血再灌注大鼠血管生成素1及其受体Tie-2的影响[J].中国康复理论与实践,2015(01)9-11.
[12] Wang W,Xu J,Li L,et al. Neuroprotective effect of morroniside on focal cerebral ischemia in rats[J]. Brain Res Bull,2010,83(5):196-201.
[13]相婕,许栋明,王文,等.莫诺苷对大鼠局灶性脑缺血再灌注损伤神经功能的影响[J].中国比较医学杂志2010(01):10-14.
[14] Longa EZ,Weinstein PR,Carlson S,et al. Reversible middle cerebral artery occlusion without craniectomy in rats[J]. Stroke,1989,20(1):84-91.
[15] Bederson JB,Pitts LH,Germano SM,et al. Evaluation of 2,3,5-triphenyltetrazolium chloride as a stain for detection and quantification of experimental cerebral infarction in rats[J].Stroke,1986,17(6):1304.
[16]但毕堂,彭小祥,陈小奇,等.急性缺血性脑卒中时间窗内的动静脉溶栓分层治疗的对比研究[J].卒中与神经疾病,2014(06):334-336.
[17] Amantea D,Certo M,Russo R,et al. Early reperfusion injury is associated to MMP2 and IL-1βelevation in cortical neurons of rats subjected to middle cerebral artery occlusion[J].Neuroscience,2014,277:755.
[18] Green AR. Pharmacological approaches to acute ischaemic stroke:reperfusion certainly,neuroprotection possibly[J]. Br J Pharmacol,2008,153(S1):S325-S338.
[19] Ruan L,Wang B,Zhuge Q,et al. Coupling of neurogenesis and angiogenesis after ischemic stroke[J]. Brain Res,2015,1623:166-173.
[20] Banerjee S, Bentley P, Hamady M, et al. Intra-arterial immunoselected CD34+stem cells for acute ischemic stroke[J].Stem Cells Transl Med,2014,3(11):1322-1330.
[21] Zhan K,Bai L,Xu J. Role of vascular endothelial progenitor cells in construction of new vascular loop[J]. Microvasc Res,2013,90:1-11.
[22] Paczkowska E, Larysz B, Rzeuski R, et al. Human hematopoietic stem/progenitor-enriched CD34+cells are mobilized into peripheral blood during stress related to ischemic stroke or acute myocardial infarction[J].Eur J Haematol,2005,75(6):461-467.
[23] Olsen JJ,Pohl SO, Deshmukh A, et al. The role of wnt signalling in angiogenesis[J] Clin Biochem Rev,2017,38(3):131-142.
[24] Palmer TD,Willhoite AR,Gage FH. Vascular niche for adult hippocampal neurogenesis[J]. J Comp Neurol,2000,425(4):479-494.