Ferroptosis is an iron-dependent novel cell death pathway. Deferoxamine, a ferroptosis inhibitor, has been reported to promote spinal cord injury repair. It has yet to be clarified whether ferroptosis inhibition repre...Ferroptosis is an iron-dependent novel cell death pathway. Deferoxamine, a ferroptosis inhibitor, has been reported to promote spinal cord injury repair. It has yet to be clarified whether ferroptosis inhibition represents the mechanism of action of Deferoxamine on spinal cord injury recovery. A rat model of Deferoxamine at thoracic 10 segment was established using a modified Allen's method. Ninety 8-week-old female Wistar rats were used. Rats in the Deferoxamine group were intraperitoneally injected with 100 mg/kg Deferoxamine 30 minutes before injury. Simultaneously, the Sham and Deferoxamine groups served as controls. Drug administration was conducted for 7 consecutive days. The results were as follows:(1) Electron microscopy revealed shrunken mitochondria in the spinal cord injury group.(2) The Basso, Beattie and Bresnahan locomotor rating score showed that recovery of the hindlimb was remarkably better in the Deferoxamine group than in the spinal cord injury group.(3) The iron concentration was lower in the Deferoxamine group than in the spinal cord injury group after injury.(4) Western blot assay revealed that, compared with the spinal cord injury group, GPX4, xCT, and glutathione expression was markedly increased in the Deferoxamine group.(5) Real-time polymerase chain reaction revealed that, compared with the Deferoxamine group, mRNA levels of ferroptosis-related genes Acyl-CoA synthetase family member 2(ACSF2) and iron-responsive element-binding protein 2(IREB2) were up-regulated in the Deferoxamine group.(6) Deferoxamine increased survival of neurons and inhibited gliosis. These findings confirm that Deferoxamine can repair spinal cord injury by inhibiting ferroptosis. Targeting ferroptosis is therefore a promising therapeutic approach for spinal cord injury.展开更多
Cardiovascular disease is the most important factor that affect the lifetime of uremia patients. Recently, scientists pay closer attention to study the mechanism of cardiac injury in uremia patients. In this article, ...Cardiovascular disease is the most important factor that affect the lifetime of uremia patients. Recently, scientists pay closer attention to study the mechanism of cardiac injury in uremia patients. In this article, we will make an overview on mechanism of cardiac injure caused by uremia toxin, secondary hyperparathyroidism, calcium-phosphorus metabolic disorder, rennin-angiotensin-aldosterone system.展开更多
Expansion of the secondary injury following primary spinal cord injury is a major pathological event that increases destruction in the spinal cord, so measures to reduce secondary injury are needed. Our previous study...Expansion of the secondary injury following primary spinal cord injury is a major pathological event that increases destruction in the spinal cord, so measures to reduce secondary injury are needed. Our previous study demonstrated that, at the front of the expanding secondary injury in the spinal cord, there is an ischemic area in which many neurons can still be rescued. Therefore, enhancement of blood circulation in the cord may be helpful, and indeed, we found that a traditional Chinese medicine, shu-xue-tong, efficiently reduces the secondary injury. The aim of the present study was to investigate the effect of reducing fibrinogen with Batroxobin, a drug widely used clinically for ischemia, in rats with spinal cord contusion. We found that both 2 and 4 Batroxobin units （BU）/kg efficiently decreased the plasma fibrinogen, and 2 BU/kg significantly increased spinal blood flow, enhanced neuronal survival, mitigated astrocyte and microglia activation, and improved locomotor recovery. However, 4 BU/kg had no effect on the secondary spinal cord injury. These data suggest that Batroxobin has multiple beneficial effects on spinal cord injury, indicating a potential clinical application.展开更多
Lithium promotes autophagy and has a neuroprotective effect on spinal cord injury（SCI）; however, the underlying mechanisms remain unclear. Therefore, in this study, we investigated the effects of lithium and the aut...Lithium promotes autophagy and has a neuroprotective effect on spinal cord injury（SCI）; however, the underlying mechanisms remain unclear. Therefore, in this study, we investigated the effects of lithium and the autophagy inhibitor 3-methyladenine（3-MA） in a rat model of SCI. The rats were randomly assigned to the SCI, lithium, 3-MA and sham groups. In the 3-MA group, rats were intraperitoneally injected with 3-MA（3 mg/kg） 2 hours before SCI. In the lithium and 3-MA groups, rats were intraperitoneally injected with lithium（LiCl; 30 mg/kg） 6 hours after SCI and thereafter once daily until sacrifice. At 2, 3 and 4 weeks after SCI, neurological function and diffusion tensor imaging indicators were remarkably improved in the lithium group compared with the SCI and 3-MA groups. The Basso, Beattie and Bresnahan locomotor rating scale score and fractional anisotropy values were increased, and the apparent diffusion coefficient value was decreased. Immunohistochemical staining showed that immunoreactivities for Beclin-1 and light-chain 3 B peaked 1 day after SCI in the lithium and SCI groups. Immunoreactivities for Beclin-1 and light-chain 3 B were weaker in the 3-MA group than in the SCI group, indicating that 3-MA inhibits lithium-induced autophagy. Furthermore, NeuN＋ neurons were more numerous in the lithium group than in the SCI and 3-MA groups, with the fewest in the latter. Our findings show that lithium reduces neuronal damage after acute SCI and promotes neurological recovery by inducing autophagy. The neuroprotective mechanism of action may not be entirely dependent on the enhancement of autophagy, and furthermore, 3-MA might not completely inhibit all autophagy pathways.展开更多
目的:探讨丹参注射液联合神经节苷脂辅助治疗康复期脊髓损伤(SCI)患者的临床疗效,挖掘其作用机制。方法:将新疆石河子大学第一附属医院收治的113例脊髓损伤患者随机分为对照组(n=25)、丹参注射液组(n=28)、神经节苷脂组(n=30)和联合组(n...目的:探讨丹参注射液联合神经节苷脂辅助治疗康复期脊髓损伤(SCI)患者的临床疗效,挖掘其作用机制。方法:将新疆石河子大学第一附属医院收治的113例脊髓损伤患者随机分为对照组(n=25)、丹参注射液组(n=28)、神经节苷脂组(n=30)和联合组(n=30),对照组患者给予正常康复训练,神经节苷脂组在对照组基础上,给予静脉滴注神经节苷脂治疗60mg,每日1次,丹参注射液组在对照组基础上给予静脉滴注丹参注射液治疗10 m L,每日1次,联合组在对照组治疗基础上给予神经节苷脂联合丹参注射液治疗,连续治疗20 d,停药10 d。比较两组患者的治疗总有效率和不良反应发生率,同时于治疗前后,比较各炎症因子水平和运动、痛觉及触觉等神经功能康复指标评分;采用ELISA法检测各组患者治疗前后血清中炎症相关因子TNF-α、IL-8、IL-1β及氧化应激相关因子SOD、MDA、VE的表达。结果:联合组疗效最佳,总有效率为83.33%,高于对照组(60%)、丹参注射液组(75%)及神经节苷脂(66.67%);联合组患者运动、痛觉及触觉的ASIA评分均明显高于对照组、丹参注射液组及神经节苷脂组(P<0.05),且联合组肌力恢复正常时间、住院时间及可下地行走时间均明显低于其他组(P<0.05);所有入组患者治疗后血清炎症相关因子TNF-α、IL-8、IL-1β均低于治疗前,但联合组表达最低(P<0.05);丹参注射液组及联合组患者治疗后血清SOD、VE表达升高,MDA降低(P<0.05)。结论:丹参注射液与神经节苷脂联合应用有助于康复期SCI患者恢复,预防脊髓继发性损害,其作用机制可能与抗炎、抗氧化有关。展开更多
基金supported by the National Natural Science Foundation of China,No.81672171(to XY),81330042(to SQF),81620108018(to SQF),81772342the State Key Laboratory of Medicinal Chemical Biology(Nankai University),China,No.2017027
文摘Ferroptosis is an iron-dependent novel cell death pathway. Deferoxamine, a ferroptosis inhibitor, has been reported to promote spinal cord injury repair. It has yet to be clarified whether ferroptosis inhibition represents the mechanism of action of Deferoxamine on spinal cord injury recovery. A rat model of Deferoxamine at thoracic 10 segment was established using a modified Allen's method. Ninety 8-week-old female Wistar rats were used. Rats in the Deferoxamine group were intraperitoneally injected with 100 mg/kg Deferoxamine 30 minutes before injury. Simultaneously, the Sham and Deferoxamine groups served as controls. Drug administration was conducted for 7 consecutive days. The results were as follows:(1) Electron microscopy revealed shrunken mitochondria in the spinal cord injury group.(2) The Basso, Beattie and Bresnahan locomotor rating score showed that recovery of the hindlimb was remarkably better in the Deferoxamine group than in the spinal cord injury group.(3) The iron concentration was lower in the Deferoxamine group than in the spinal cord injury group after injury.(4) Western blot assay revealed that, compared with the spinal cord injury group, GPX4, xCT, and glutathione expression was markedly increased in the Deferoxamine group.(5) Real-time polymerase chain reaction revealed that, compared with the Deferoxamine group, mRNA levels of ferroptosis-related genes Acyl-CoA synthetase family member 2(ACSF2) and iron-responsive element-binding protein 2(IREB2) were up-regulated in the Deferoxamine group.(6) Deferoxamine increased survival of neurons and inhibited gliosis. These findings confirm that Deferoxamine can repair spinal cord injury by inhibiting ferroptosis. Targeting ferroptosis is therefore a promising therapeutic approach for spinal cord injury.
文摘Cardiovascular disease is the most important factor that affect the lifetime of uremia patients. Recently, scientists pay closer attention to study the mechanism of cardiac injury in uremia patients. In this article, we will make an overview on mechanism of cardiac injure caused by uremia toxin, secondary hyperparathyroidism, calcium-phosphorus metabolic disorder, rennin-angiotensin-aldosterone system.
基金supported by grants from the National Natural Science Foundation of China (81072600 and 31271583)
文摘Expansion of the secondary injury following primary spinal cord injury is a major pathological event that increases destruction in the spinal cord, so measures to reduce secondary injury are needed. Our previous study demonstrated that, at the front of the expanding secondary injury in the spinal cord, there is an ischemic area in which many neurons can still be rescued. Therefore, enhancement of blood circulation in the cord may be helpful, and indeed, we found that a traditional Chinese medicine, shu-xue-tong, efficiently reduces the secondary injury. The aim of the present study was to investigate the effect of reducing fibrinogen with Batroxobin, a drug widely used clinically for ischemia, in rats with spinal cord contusion. We found that both 2 and 4 Batroxobin units （BU）/kg efficiently decreased the plasma fibrinogen, and 2 BU/kg significantly increased spinal blood flow, enhanced neuronal survival, mitigated astrocyte and microglia activation, and improved locomotor recovery. However, 4 BU/kg had no effect on the secondary spinal cord injury. These data suggest that Batroxobin has multiple beneficial effects on spinal cord injury, indicating a potential clinical application.
基金supported by the Beijing Excellent Talent Training Funding in China,No.2017000021469G215(to DZ)the Youth Science Foundation of Beijing Tiantan Hospital of China,No.2016-YQN-14(to DZ)+1 种基金the Natural Science Foundation of Capital Medical University of China,No.PYZ2017082(to DZ)the Xi’an Science and Technology Project in China,No.2016048SF/YX04(3)(to XHL)
文摘Lithium promotes autophagy and has a neuroprotective effect on spinal cord injury（SCI）; however, the underlying mechanisms remain unclear. Therefore, in this study, we investigated the effects of lithium and the autophagy inhibitor 3-methyladenine（3-MA） in a rat model of SCI. The rats were randomly assigned to the SCI, lithium, 3-MA and sham groups. In the 3-MA group, rats were intraperitoneally injected with 3-MA（3 mg/kg） 2 hours before SCI. In the lithium and 3-MA groups, rats were intraperitoneally injected with lithium（LiCl; 30 mg/kg） 6 hours after SCI and thereafter once daily until sacrifice. At 2, 3 and 4 weeks after SCI, neurological function and diffusion tensor imaging indicators were remarkably improved in the lithium group compared with the SCI and 3-MA groups. The Basso, Beattie and Bresnahan locomotor rating scale score and fractional anisotropy values were increased, and the apparent diffusion coefficient value was decreased. Immunohistochemical staining showed that immunoreactivities for Beclin-1 and light-chain 3 B peaked 1 day after SCI in the lithium and SCI groups. Immunoreactivities for Beclin-1 and light-chain 3 B were weaker in the 3-MA group than in the SCI group, indicating that 3-MA inhibits lithium-induced autophagy. Furthermore, NeuN＋ neurons were more numerous in the lithium group than in the SCI and 3-MA groups, with the fewest in the latter. Our findings show that lithium reduces neuronal damage after acute SCI and promotes neurological recovery by inducing autophagy. The neuroprotective mechanism of action may not be entirely dependent on the enhancement of autophagy, and furthermore, 3-MA might not completely inhibit all autophagy pathways.
文摘目的:探讨丹参注射液联合神经节苷脂辅助治疗康复期脊髓损伤(SCI)患者的临床疗效,挖掘其作用机制。方法:将新疆石河子大学第一附属医院收治的113例脊髓损伤患者随机分为对照组(n=25)、丹参注射液组(n=28)、神经节苷脂组(n=30)和联合组(n=30),对照组患者给予正常康复训练,神经节苷脂组在对照组基础上,给予静脉滴注神经节苷脂治疗60mg,每日1次,丹参注射液组在对照组基础上给予静脉滴注丹参注射液治疗10 m L,每日1次,联合组在对照组治疗基础上给予神经节苷脂联合丹参注射液治疗,连续治疗20 d,停药10 d。比较两组患者的治疗总有效率和不良反应发生率,同时于治疗前后,比较各炎症因子水平和运动、痛觉及触觉等神经功能康复指标评分;采用ELISA法检测各组患者治疗前后血清中炎症相关因子TNF-α、IL-8、IL-1β及氧化应激相关因子SOD、MDA、VE的表达。结果:联合组疗效最佳,总有效率为83.33%,高于对照组(60%)、丹参注射液组(75%)及神经节苷脂(66.67%);联合组患者运动、痛觉及触觉的ASIA评分均明显高于对照组、丹参注射液组及神经节苷脂组(P<0.05),且联合组肌力恢复正常时间、住院时间及可下地行走时间均明显低于其他组(P<0.05);所有入组患者治疗后血清炎症相关因子TNF-α、IL-8、IL-1β均低于治疗前,但联合组表达最低(P<0.05);丹参注射液组及联合组患者治疗后血清SOD、VE表达升高,MDA降低(P<0.05)。结论:丹参注射液与神经节苷脂联合应用有助于康复期SCI患者恢复,预防脊髓继发性损害,其作用机制可能与抗炎、抗氧化有关。
