Somatosensory evoked potentials(SEPs)have been widely used to assess neurological function in clinical practice.A good understanding of the association between SEP signals and neurological function is helpful for prec...Somatosensory evoked potentials(SEPs)have been widely used to assess neurological function in clinical practice.A good understanding of the association between SEP signals and neurological function is helpful for precise diagnosis of impairment location.Previous studies on SEPs have been reported in animal models.However,few studies have reported the relationships between SEP waveforms in animals and those in humans.In this study,we collected normal SEP waveforms and decomposed them into specific time–frequency components(TFCs).Our results showed three stable TFC distribution regions in intact goats and rats and in humans.After we induced spinal cord injury in the animal models,a greater number of small TFC distribution regions were observed in the injured goat and rat groups than in the normal group.Moreover,there were significant correlations(P<0.05)and linear relationships between the main SEP TFCs of the human group and those of the goat and rat groups.A stable TFC distribution of SEP components was observed in the human,goat and rat groups,and the TFC distribution modes were similar between the three groups.Results in various animal models in this study could be translated to future clinical studies based on SEP TFC analysis.Human studies were approved by the Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West Cluster(approval No.UM 05-312 T/975)on December 5,2005.Rat experiments were approved by the Committee on the Use of Live Animals in Teaching and Research of Li Ka Shing Faculty of Medicine of the University of Hong Kong(approval No.CULART 2912-12)on January 28,2013.Goat experiments were approved by the Animal Ethics Committee of Affiliated Hospital of Guangdong Medical University(approval No.GDY2002132)on March 5,2018.展开更多
Background:Prevention of diabetic heart myocardial ischemia-reperfusion(IR)injury(MIRI)is challenging.Propofol attenuates MIRI through its reactive oxygen species scavenging property at high doses,while its use at hig...Background:Prevention of diabetic heart myocardial ischemia-reperfusion(IR)injury(MIRI)is challenging.Propofol attenuates MIRI through its reactive oxygen species scavenging property at high doses,while its use at high doses causes hemodynamic instability.Salvianolic acid A(SAA)is a potent antioxidant that confers protection against MIRI.Both propofol and SAA affect metabolic profiles through regulating Adenosine 5‘-monophosphate-activated protein kinase(AMPK).The aim of this study was to investigate the protective effects and underlying mechanisms of low doses of propofol combined with SAA against diabetic MIRI.Methods:Diabetes was induced in mice by a high-fat diet followed by streptozotocin injection,and MIRI was induced by coronary artery occlusion and reperfusion.Mice were treated with propofol at 46 mg/kg/h without or with SAA at 10 mg/kg/h during IR.Cardiac origin H9c2 cells were exposed to high glucose(HG)and palmitic acid(PAL)for 24 h in the absence or presence of cluster of differentiation 36(CD36)overexpression or AMPK gene knockdown,followed by hypoxia/reoxygenation(HR)for 6 and 12 h.Results:Diabetes-exacerbated MIRI is evidenced as significant increases in post-ischemic infarction with reductions in phosphorylated(p)-AMPK and increases in CD36 and ferroptosis.Propofol moderately yet significantly attenuated all the abovementioned changes,while propofol plus SAA conferred superior protection against MIRI to that of propofol.In vitro,exposure of H9c2 cells under HG and PAL decreased cell viability and increased oxidative stress that was concomitant with increased levels of ferroptosis and a significant increase in CD36,while p-AMPK was significantly reduced.Co-administration of low concentrations of propofol and SAA at 12.5μM in H9c2 cells significantly reduced oxidative stress,ferroptosis and CD36 expression,while increasing pAMPK compared to the effects of propofol at 25μM.Moreover,either CD36 overexpression or AMPK silence significantly exacerbated HR-induced cellular injuries and ferroptosis,and canceled propofol-and SAA-mediated protection.Notably,p-AMPK expression was downregulated after CD36 overexpression,while AMPK knockdown did not affect CD36 expression.Conclusions:Combinational usage of propofol and SAA confers superior cellular protective effects to the use of high-dose propofol alone,and it does so through inhibiting HR-induced CD36 overexpression to upregulate p-AMPK.展开更多
基金supported by the National Natural Science Foundation of China,No.81871768(to YH)the Natural Science Foundation of Tianjin of China,No.18JCYBJC29600(to HYC)High Level-Hospital Program,Health Commission of Guangdong Province of China,No.HKUSZH201902011(to YH).
文摘Somatosensory evoked potentials(SEPs)have been widely used to assess neurological function in clinical practice.A good understanding of the association between SEP signals and neurological function is helpful for precise diagnosis of impairment location.Previous studies on SEPs have been reported in animal models.However,few studies have reported the relationships between SEP waveforms in animals and those in humans.In this study,we collected normal SEP waveforms and decomposed them into specific time–frequency components(TFCs).Our results showed three stable TFC distribution regions in intact goats and rats and in humans.After we induced spinal cord injury in the animal models,a greater number of small TFC distribution regions were observed in the injured goat and rat groups than in the normal group.Moreover,there were significant correlations(P<0.05)and linear relationships between the main SEP TFCs of the human group and those of the goat and rat groups.A stable TFC distribution of SEP components was observed in the human,goat and rat groups,and the TFC distribution modes were similar between the three groups.Results in various animal models in this study could be translated to future clinical studies based on SEP TFC analysis.Human studies were approved by the Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West Cluster(approval No.UM 05-312 T/975)on December 5,2005.Rat experiments were approved by the Committee on the Use of Live Animals in Teaching and Research of Li Ka Shing Faculty of Medicine of the University of Hong Kong(approval No.CULART 2912-12)on January 28,2013.Goat experiments were approved by the Animal Ethics Committee of Affiliated Hospital of Guangdong Medical University(approval No.GDY2002132)on March 5,2018.
基金supported by the National Natural Science Fundation of China(81970247,82270306)Research Grant Council GRF Grant(17118619)in part by Guangdong Provincial Basic and Applied Basic Science Project(2021A1515011434).
文摘Background:Prevention of diabetic heart myocardial ischemia-reperfusion(IR)injury(MIRI)is challenging.Propofol attenuates MIRI through its reactive oxygen species scavenging property at high doses,while its use at high doses causes hemodynamic instability.Salvianolic acid A(SAA)is a potent antioxidant that confers protection against MIRI.Both propofol and SAA affect metabolic profiles through regulating Adenosine 5‘-monophosphate-activated protein kinase(AMPK).The aim of this study was to investigate the protective effects and underlying mechanisms of low doses of propofol combined with SAA against diabetic MIRI.Methods:Diabetes was induced in mice by a high-fat diet followed by streptozotocin injection,and MIRI was induced by coronary artery occlusion and reperfusion.Mice were treated with propofol at 46 mg/kg/h without or with SAA at 10 mg/kg/h during IR.Cardiac origin H9c2 cells were exposed to high glucose(HG)and palmitic acid(PAL)for 24 h in the absence or presence of cluster of differentiation 36(CD36)overexpression or AMPK gene knockdown,followed by hypoxia/reoxygenation(HR)for 6 and 12 h.Results:Diabetes-exacerbated MIRI is evidenced as significant increases in post-ischemic infarction with reductions in phosphorylated(p)-AMPK and increases in CD36 and ferroptosis.Propofol moderately yet significantly attenuated all the abovementioned changes,while propofol plus SAA conferred superior protection against MIRI to that of propofol.In vitro,exposure of H9c2 cells under HG and PAL decreased cell viability and increased oxidative stress that was concomitant with increased levels of ferroptosis and a significant increase in CD36,while p-AMPK was significantly reduced.Co-administration of low concentrations of propofol and SAA at 12.5μM in H9c2 cells significantly reduced oxidative stress,ferroptosis and CD36 expression,while increasing pAMPK compared to the effects of propofol at 25μM.Moreover,either CD36 overexpression or AMPK silence significantly exacerbated HR-induced cellular injuries and ferroptosis,and canceled propofol-and SAA-mediated protection.Notably,p-AMPK expression was downregulated after CD36 overexpression,while AMPK knockdown did not affect CD36 expression.Conclusions:Combinational usage of propofol and SAA confers superior cellular protective effects to the use of high-dose propofol alone,and it does so through inhibiting HR-induced CD36 overexpression to upregulate p-AMPK.
