目的探讨三七总皂苷(total saponins of panax noto ginseseng,PNS)对局灶性脑梗死大鼠海马CA1区神经元保护及促进神经重塑的机制。方法将动物随机分为Y27632组、PNS加Y27632组、假手术组和手术组,对除了假手术组外的所有动物,建立大鼠...目的探讨三七总皂苷(total saponins of panax noto ginseseng,PNS)对局灶性脑梗死大鼠海马CA1区神经元保护及促进神经重塑的机制。方法将动物随机分为Y27632组、PNS加Y27632组、假手术组和手术组,对除了假手术组外的所有动物,建立大鼠大脑中动脉阻塞(MCAO)模型,造模成功且未分组的动物根据Longa评分和体重进行随机分组,分别为模型组、PNS组、尼莫地平组。观察造模7d后大鼠一般活动状态、体重指数和海马CA1区神经元形态学及Nogo-A、NgR1和RhoA蛋白表达变化。结果与假手术组比较,模型组Nogo-A、NgR1和RhoA蛋白表达增多(P<0.01);与模型组比较,PNS组大鼠Nogo-A、NgR1和RhoA蛋白表达均下降(P<0.05),PNS加Y27632组NgR1和RhoA蛋白表达降低(P<0.05),Y27632组RhoA蛋白表达下降(P<0.01)。结论 PNS具有与Y27632相似的作用,对脑梗死后Nogo-A/NgR1/Rho通路的上下游均有调节作用,可促进脑梗死损伤后海马神经功能重塑。展开更多
BACKGROUND: Olfactory ensheathing cell (OEC) transplantation promotes repair of spinal cord injury. Neural regeneration inhibits binding of the myelin protein Nogo to its receptor (NgR), activates downstream inhi...BACKGROUND: Olfactory ensheathing cell (OEC) transplantation promotes repair of spinal cord injury. Neural regeneration inhibits binding of the myelin protein Nogo to its receptor (NgR), activates downstream inhibitory signal RhoA, and leads to axonal degeneration. OBJECTIVE: To determine the relationship between OECs transplantation for spinal cord injury and NogoA, NgR, and RhoA protein expression in the damaged zone. DESIGN, TIME AND SETTING: A randomized, controlled, animal experiment was performed from September 2006 to May 2007 at the Key Laboratory of Environment and Genes in Xi'an Jiaotong University School of Medicine, China. MATERIALS: OECs were harvested from healthy, adult, male, Sprague Dawley rats aged 6 months. Mouse anti-rat NogoA, NgR, and RheA monoclonal antibodies were utilized for detection. METHODS: A total of 40 adult Sprague Dawley rats were randomly assigned to four groups: normal, model, OECs, and DF12, with 10 animals in each group. Transverse section spinal cord injury was established in the OECs and DF12 groups, followed by injection of 1μL OECs suspension (1×10^8/mL) or equivalent DF12 medium at 1 mm above and below the injury site. MAIN OUTCOME MEASURES: Immunohistochemistry and Western blot were utilized to detect NogoA, NgR, and RhoA expression in the spinal cord injury lesions. Morphological changes were observed by argyrophilia staining, and lower extremity function of the animals was assessed using Basso, Beattie, and Bresnahan scores. RESULTS: Eight weeks following OECs transplantation, a significant increase in new axons was observed in the OECs group, and nerve fibers crossed the injury site to repair spinal cord injury. Qualitative and quantitative results from the OECs group were superior to the model and DF12 groups. At 8 weeks after transplantation, Basso, Beattie, and Bresnahan scores were significantly greater in the OECs group compared with the model and DF12 groups (P 〈 0.01), but expression of NogoA, NgR, and RhoA protein was significantly decreased compared with the model and DF12 groups (P〈 0.05). CONCLUSION: OEC transplantation could inhibit NogoA, NgR, and RhoA expression in spinal cord injury lesions, thereby promoting repair of spinal cord injury.展开更多
Treating stroke or restoring brain function after stroke remains challenging for clinicians[1,2].Researchers have largely focused on developing neuroprotective strategies and translating these discoveries from rodent ...Treating stroke or restoring brain function after stroke remains challenging for clinicians[1,2].Researchers have largely focused on developing neuroprotective strategies and translating these discoveries from rodent experiments to the clinical setting;however,these have been typified by several failures[2].It is known that astrocytes play a crucial role in the pathogenesis of ischemic stroke[3,4].They are activated in response to stimuli arising from injury,characterized by drastic changes to their morphology and function-associated gene expression.Reactive astrocytes exacerbate secondary neurodegeneration(repair of nervous tissue by the generation of new neurons,glial cells,axons,myelin,or synapses)[5]as well as provide neuroprotection during CNS pathologies[6].It is worth noting that myelin-related neurite growth inhibitors induce the suppression of axon regeneration after stroke[7].展开更多
文摘目的探讨三七总皂苷(total saponins of panax noto ginseseng,PNS)对局灶性脑梗死大鼠海马CA1区神经元保护及促进神经重塑的机制。方法将动物随机分为Y27632组、PNS加Y27632组、假手术组和手术组,对除了假手术组外的所有动物,建立大鼠大脑中动脉阻塞(MCAO)模型,造模成功且未分组的动物根据Longa评分和体重进行随机分组,分别为模型组、PNS组、尼莫地平组。观察造模7d后大鼠一般活动状态、体重指数和海马CA1区神经元形态学及Nogo-A、NgR1和RhoA蛋白表达变化。结果与假手术组比较,模型组Nogo-A、NgR1和RhoA蛋白表达增多(P<0.01);与模型组比较,PNS组大鼠Nogo-A、NgR1和RhoA蛋白表达均下降(P<0.05),PNS加Y27632组NgR1和RhoA蛋白表达降低(P<0.05),Y27632组RhoA蛋白表达下降(P<0.01)。结论 PNS具有与Y27632相似的作用,对脑梗死后Nogo-A/NgR1/Rho通路的上下游均有调节作用,可促进脑梗死损伤后海马神经功能重塑。
基金Doctoral Fund of Ministry of Education of China,No.20050698043
文摘BACKGROUND: Olfactory ensheathing cell (OEC) transplantation promotes repair of spinal cord injury. Neural regeneration inhibits binding of the myelin protein Nogo to its receptor (NgR), activates downstream inhibitory signal RhoA, and leads to axonal degeneration. OBJECTIVE: To determine the relationship between OECs transplantation for spinal cord injury and NogoA, NgR, and RhoA protein expression in the damaged zone. DESIGN, TIME AND SETTING: A randomized, controlled, animal experiment was performed from September 2006 to May 2007 at the Key Laboratory of Environment and Genes in Xi'an Jiaotong University School of Medicine, China. MATERIALS: OECs were harvested from healthy, adult, male, Sprague Dawley rats aged 6 months. Mouse anti-rat NogoA, NgR, and RheA monoclonal antibodies were utilized for detection. METHODS: A total of 40 adult Sprague Dawley rats were randomly assigned to four groups: normal, model, OECs, and DF12, with 10 animals in each group. Transverse section spinal cord injury was established in the OECs and DF12 groups, followed by injection of 1μL OECs suspension (1×10^8/mL) or equivalent DF12 medium at 1 mm above and below the injury site. MAIN OUTCOME MEASURES: Immunohistochemistry and Western blot were utilized to detect NogoA, NgR, and RhoA expression in the spinal cord injury lesions. Morphological changes were observed by argyrophilia staining, and lower extremity function of the animals was assessed using Basso, Beattie, and Bresnahan scores. RESULTS: Eight weeks following OECs transplantation, a significant increase in new axons was observed in the OECs group, and nerve fibers crossed the injury site to repair spinal cord injury. Qualitative and quantitative results from the OECs group were superior to the model and DF12 groups. At 8 weeks after transplantation, Basso, Beattie, and Bresnahan scores were significantly greater in the OECs group compared with the model and DF12 groups (P 〈 0.01), but expression of NogoA, NgR, and RhoA protein was significantly decreased compared with the model and DF12 groups (P〈 0.05). CONCLUSION: OEC transplantation could inhibit NogoA, NgR, and RhoA expression in spinal cord injury lesions, thereby promoting repair of spinal cord injury.
基金supported by the Science and Technology Developmental Plan of Henan Province,China(232102520025)The National Foreign Expert Program of China(QN2022026001L).
文摘Treating stroke or restoring brain function after stroke remains challenging for clinicians[1,2].Researchers have largely focused on developing neuroprotective strategies and translating these discoveries from rodent experiments to the clinical setting;however,these have been typified by several failures[2].It is known that astrocytes play a crucial role in the pathogenesis of ischemic stroke[3,4].They are activated in response to stimuli arising from injury,characterized by drastic changes to their morphology and function-associated gene expression.Reactive astrocytes exacerbate secondary neurodegeneration(repair of nervous tissue by the generation of new neurons,glial cells,axons,myelin,or synapses)[5]as well as provide neuroprotection during CNS pathologies[6].It is worth noting that myelin-related neurite growth inhibitors induce the suppression of axon regeneration after stroke[7].