有氧运动和黑果枸杞多糖对慢性脑缺血小鼠的干预及Notch通路相关因子的组织差异表达
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摘要
目的观察有氧运动(SW)与黑果枸杞多糖(LRM)对慢性脑缺血小鼠的干预作用以及Notch通路相关因子在脑和血液组织差异表达的比较分析。方法 50只雄性KM小鼠,构建慢性脑缺血损伤模型,随机分为模型组(M组)、干预组[包括SW组、LRM组、LRM+SW组、阳性对照组(BLDJ组)],干预组分别进行中等强度有氧运动和/或黑果枸杞多糖(200 mg/kg)灌胃。设假手术组(SO组,10只)。各组进行神经行为学评估;Nissl染色进行脑组织显微结构形态学观察;免疫组化检测相关因子的蛋白表达水平;实时荧光定量技术检测脑组织和血液中Notch通路相关因子的表达。结果脑组织损伤得分M>SW>LRM>BLDJ>LRM+SW>SO(P<0.05)。M组脑组织神经元结构出现大面积损伤,LRM+SW组干预效果最佳(P<0.01)。SO组小鼠脑Notch1、Jagged1、NCX1、SYP阳性表达最高,干预组阳性表达均高于M组(P<0.01,P<0.05);LRM+SW组阳性表达较LRM组合BLDJ组高(P<0.01)。干预组调节神经细胞修复相关因子在组织和血液中的表达明显高于M组(P<0.01),其中LRM+SW组表达水平最高。Notch1、Jagged1、NCX1在组织和血液中的表达呈正相关,且在组织中的表达含量高于血液中的表达(P<0.05)。结论有氧运动与黑果枸杞多糖对小鼠慢性脑缺血引发的脑损伤有明显缓解作用,能不同程度促进神经元修复,且两者联合效果更为显著,其作用可能是通过调节Nocth通路中相关神经修复因子的表达,从而抑制脑损伤。
Aim To observe the effect of aerobic exercise and Lycium ruthenicum murr( LRM) polysaccharides on chronic cerebral ischemia and the differential expression of Notch channel related factors in brain and blood tissue.Methods 50 male KM mice were used to construct the model of chronic cerebral ischemia. They were randomly divided into model group( M group),and the intervention group including SW group,LRM group,LRM + SW group,positive control group( BLDJ group). The mice in the intervention group were treated with moderate intensity aerobic exercise and/or Lycium ruthenicum Murr polysaccharides( 200 mg/kg). False surgery group( SO group). Neurobehavioral assessment was performed in each group; Nissl staining was used for brain tissue microstructure morphological observation;immunohistochemistry was used to detect the protein expression level of related factors. Real-time fluorescence quantitative technique was used to detect the expression of Notch pathway-related factors in brain tissue and blood. Results Brain tissue injury score was M group> SW group> LRM group> BLDJ group> LRM + SW group> SO group( P<0.05). Brain tissue neuronal structure of M group had a large area of injury,LRM + SW group had the best effect( P<0.01). The expression of Notch1,Jagged1,NCX1 and SYP in the SO group was the highest,the positive expression in the intervention group was higher than that in the M group( P<0.01,P<0.05). The positive expression of LRM + SW group was higher than that of LRM group( P<0. 01). The intervention group regulating the expression of nerve cell repair related factors in tissues and blood was significantly higher than the M group( P< 0. 01),and the LRM + SW group had the highest level of expression. Notch1,Jagged1,NCX1 are positively correlated with tissue and blood,and the expression in the tissue is higher than the expression in the blood( P< 0. 05). Conclusion Aerobic exercise and Lycium ruthenicum Murr polysaccharides have a significant reduction in brain damage caused by chronic brain ischemia in mice,which can promote neuronal repair to varying degrees,and the combined effect between the two is more significant.Its role may be through the regulation of Notch channel related nerve repair factor expression,thereby inhibiting brain injury.
Aim To observe the effect of aerobic exercise and Lycium ruthenicum murr( LRM) polysaccharides on chronic cerebral ischemia and the differential expression of Notch channel related factors in brain and blood tissue.Methods 50 male KM mice were used to construct the model of chronic cerebral ischemia. They were randomly divided into model group( M group),and the intervention group including SW group,LRM group,LRM + SW group,positive control group( BLDJ group). The mice in the intervention group were treated with moderate intensity aerobic exercise and/or Lycium ruthenicum Murr polysaccharides( 200 mg/kg). False surgery group( SO group). Neurobehavioral assessment was performed in each group; Nissl staining was used for brain tissue microstructure morphological observation;immunohistochemistry was used to detect the protein expression level of related factors. Real-time fluorescence quantitative technique was used to detect the expression of Notch pathway-related factors in brain tissue and blood. Results Brain tissue injury score was M group> SW group> LRM group> BLDJ group> LRM + SW group> SO group( P<0.05). Brain tissue neuronal structure of M group had a large area of injury,LRM + SW group had the best effect( P<0.01). The expression of Notch1,Jagged1,NCX1 and SYP in the SO group was the highest,the positive expression in the intervention group was higher than that in the M group( P<0.01,P<0.05). The positive expression of LRM + SW group was higher than that of LRM group( P<0. 01). The intervention group regulating the expression of nerve cell repair related factors in tissues and blood was significantly higher than the M group( P< 0. 01),and the LRM + SW group had the highest level of expression. Notch1,Jagged1,NCX1 are positively correlated with tissue and blood,and the expression in the tissue is higher than the expression in the blood( P< 0. 05). Conclusion Aerobic exercise and Lycium ruthenicum Murr polysaccharides have a significant reduction in brain damage caused by chronic brain ischemia in mice,which can promote neuronal repair to varying degrees,and the combined effect between the two is more significant.Its role may be through the regulation of Notch channel related nerve repair factor expression,thereby inhibiting brain injury.
引文
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[12]赵秀芹,毛文静,李世英,等.丁苯酞对局灶性脑缺血再灌注大鼠海马CA1区神经细胞凋亡SIRT1及PGC-1α表达的影响[J].中国动脉硬化杂志,2016,26(8):775-776.
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[14]Bederson JB,Pitts LH,Tsuji M,Nishimura MC,et al.Rat middle cerebral artery occlusion:evaluation of the model and development of a neurologic examination[J].Stroke,1986,17(5):472-476.
[15]Kim S,Chin YW,Cho J.Protection of cultured cortical neurons by luteolin against oxidative damage through inhibition of apoptosis and induction of heme oxygenase-1[J].BP B,2017,40(3):256-265.
[16]王金祥,周芳,朱光旭,等.Notch信号通路介导血小板源生长因梓AA诱导的血管平滑肌细胞增殖和迁移[J].中国动脉硬化杂志,2016,24(9):887-888.
[17]Xin G,Tao S,Li JH,et al.Electroacupuncture in the repair of spinal cord injury:inhibiting the notch signaling pathway and promoting neural stem cell proliferation[J].NRR,2015,3(10):395-396.
[18]Liu J,Xue J,Zhang HC.Oning expression and purification of cold inducible RNA-binding protein and its neuroprotective mechanism of action[J].BR,2015,15(4):189-195.
[19]Cheah M,Andrews MR.Targeting cell surface receptors for axon regeneration in the central nervous system.john van geest centre for brain repair[J].NRR,2016,11(12):1 884-887.
[2]刘雨佳,李娜,石丽君,等.有氧运动抑制衰老大鼠脑动脉平滑肌STOC/BKCa功能下调[J].中国动脉硬化杂志,2015,23(7):650-651.
[3]郭音.有氧运动与黑果枸杞多糖改善小鼠阻塞性黄疸致肝损伤的研究[D].长沙:湖南师范大学,2016:1-2.
[4]马玉婷.黑果枸杞酒渣花色苷和多糖制备及其功能研究[D].乌鲁木齐:新疆师范大学,2012:4-5.
[5]Zhang HP,Sun YY,Chen XM,et al.The neuroprotective effects of isoflurane preconditioning in a murine transient global cerebral ischemia-reperfusion model:the role of the notch signaling pathway[J].Neuromolecular Med,2014,16(7):191-204.
[6]Yoshizaki K,Adachi K,Kataoka S,et al.Chronic cerebral hypoperfusion induced by right unilateral common carotid artery occlusion causes delayed white matter lesions and cognitive impairment in adult mice[J].Exp Neurol,2008,210(2):585-591.
[7]李娜.构祀中色素、构祀黄酮及构祀多糖提取工艺的研究[D].兰州:兰州理工大学,2010:47-53.
[8]Clark WM,Lessov NS,Dixon MP,et al.Monofilament intraluminal middle cerebral artery occlusion in the mouse[J].Neurol Res,1997,19(6):641-648.
[9]Zhao Y,Gong CX.From chronic cerebral hypoperfusion to alzheimer-like brain pathology and neurodegeneration[J].Cell Mol Neurobiol,2015,35(12):101-110.
[10]何金婷.Notch通路在脑缺血损伤中的作用及信号转导机制研究[D].吉林长春:吉林大学,2012:18-19.
[11]冯乐霄,陈涛,刘文博,等.Homer1a基因敲除对小鼠局灶性脑缺血再灌注损伤的作用[J].现代生物医学进展,2015,9(15):1 614-615.
[12]赵秀芹,毛文静,李世英,等.丁苯酞对局灶性脑缺血再灌注大鼠海马CA1区神经细胞凋亡SIRT1及PGC-1α表达的影响[J].中国动脉硬化杂志,2016,26(8):775-776.
[13]Xu WS,Sun X,Song CG.Bumetanide promotes neural precursor cell regeneration and dendritic development in the hippocampal dentate gyrus in the chronic stage of cerebral ischemia[J].NRR,2016,11(5):745-751.
[14]Bederson JB,Pitts LH,Tsuji M,Nishimura MC,et al.Rat middle cerebral artery occlusion:evaluation of the model and development of a neurologic examination[J].Stroke,1986,17(5):472-476.
[15]Kim S,Chin YW,Cho J.Protection of cultured cortical neurons by luteolin against oxidative damage through inhibition of apoptosis and induction of heme oxygenase-1[J].BP B,2017,40(3):256-265.
[16]王金祥,周芳,朱光旭,等.Notch信号通路介导血小板源生长因梓AA诱导的血管平滑肌细胞增殖和迁移[J].中国动脉硬化杂志,2016,24(9):887-888.
[17]Xin G,Tao S,Li JH,et al.Electroacupuncture in the repair of spinal cord injury:inhibiting the notch signaling pathway and promoting neural stem cell proliferation[J].NRR,2015,3(10):395-396.
[18]Liu J,Xue J,Zhang HC.Oning expression and purification of cold inducible RNA-binding protein and its neuroprotective mechanism of action[J].BR,2015,15(4):189-195.
[19]Cheah M,Andrews MR.Targeting cell surface receptors for axon regeneration in the central nervous system.john van geest centre for brain repair[J].NRR,2016,11(12):1 884-887.