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
目的:研究山药水提物(aqueous extract of Dioscorea batatas,DA)对四氯化碳(CCl4)造成的小鼠急性肝损伤的改善作用。方法:60只昆明小鼠随机均分为6组:正常对照组、造模组、阳性对照组(联苯双酯组)、不同提取工艺的山药水提物A、B、C组...目的:研究山药水提物(aqueous extract of Dioscorea batatas,DA)对四氯化碳(CCl4)造成的小鼠急性肝损伤的改善作用。方法:60只昆明小鼠随机均分为6组:正常对照组、造模组、阳性对照组(联苯双酯组)、不同提取工艺的山药水提物A、B、C组,用四氯化碳造成小鼠急性肝损伤模型,测定血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、肝组织超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量。肝组织常规HE染色观察。结果:各组肝损伤模型小鼠经山药水提物A、B、C及联苯双酯干预后,血清ALT、AST水平与造模组相比显著降低(P<0.05),肝组织中SOD活性升高,MDA含量降低(P<0.05),镜检观察山药水提物A、B、C及联苯双酯组小鼠肝组织病理切片,发现山药水提物A、B、C及联苯双酯组较造模组肝组织损伤坏死明显减轻,坏死灶减少,范围减小,粒细胞浸润减少,并且山药水提物A组较B、C2组干预肝损伤效果好。结论:山药水提物能明显改善CCl4所致急性肝损伤小鼠的肝功能状况,其作用可能与抗氧化清除自由基、和增强机体清除自由基的能力有关。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.
文摘目的:研究山药水提物(aqueous extract of Dioscorea batatas,DA)对四氯化碳(CCl4)造成的小鼠急性肝损伤的改善作用。方法:60只昆明小鼠随机均分为6组:正常对照组、造模组、阳性对照组(联苯双酯组)、不同提取工艺的山药水提物A、B、C组,用四氯化碳造成小鼠急性肝损伤模型,测定血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、肝组织超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量。肝组织常规HE染色观察。结果:各组肝损伤模型小鼠经山药水提物A、B、C及联苯双酯干预后,血清ALT、AST水平与造模组相比显著降低(P<0.05),肝组织中SOD活性升高,MDA含量降低(P<0.05),镜检观察山药水提物A、B、C及联苯双酯组小鼠肝组织病理切片,发现山药水提物A、B、C及联苯双酯组较造模组肝组织损伤坏死明显减轻,坏死灶减少,范围减小,粒细胞浸润减少,并且山药水提物A组较B、C2组干预肝损伤效果好。结论:山药水提物能明显改善CCl4所致急性肝损伤小鼠的肝功能状况,其作用可能与抗氧化清除自由基、和增强机体清除自由基的能力有关。
