BACKGROUND： Studies have shown that low molecular weight heparin-superoxide dismutase conjugate exhibits a remarkable neuroprotective effect. OBJECTIVE： To investigate the effect of low molecular weight heparin-supe...BACKGROUND： Studies have shown that low molecular weight heparin-superoxide dismutase conjugate exhibits a remarkable neuroprotective effect. OBJECTIVE： To investigate the effect of low molecular weight heparin-superoxide dismutase conjugate on astrocytes in an interleukin-6 （IL-6） overexpressing mice following local cerebral ischemia. DESIGN, TIME AND SETTING： Randomized, cytological, controlled, animal study was performed in the Department of Physiology and Neuroscience, Neurology and Biochemistry and Molecular Biology, Medical University of South Carolina from January 2005 to March 2005. MATERIALS： Nine IL-6 transgenic mice, irrespective of gender, were randomly divided into three groups： sham-operated, model, and treatment, with three mice in each group. With exception of the sham-operated group, right middle cerebral artery occlusion was induced in the mice. Expression of glial fibrillary acidic protein, an astrocyte marker, was determined by immunohistochemistry. Low molecular weight heparin-superoxide dismutase conjugate was purchased from Biochemistry and Biotechnique Institute, Shandong University. METHODS： Two minutes prior to ischemia induction, 0.5 mL/kg saline or 20 000 U/kg low molecular weight heparin-superoxide dismutase conjugate were administrated via the femoral artery in the model group and treatment group, respectively. The sham-operated group underwent the same protocols, with the exception of occlusion and treatment. MAIN OUTCOME MEASURES： The number of glial fibrillary acidic protein-positive cells was quantified under light microscopy （x200）. RESULTS： In the sham-operated group, there were a large number of astrocytes in the IL-6 transgenic mice. However, the cell bodies were small, and the branches were few and thin. The number of astrocytes in the model group was remarkably less than the sham-operated group. Compared to the model and sham-operated groups, the number of astrocytes significantly increased, and the cell body became larger, following treatment with low molecular weight heparin-superoxide dismutase conjugate. Astrocytes exhibited hypertrophy and hyperplasia, and the processes became longer and thicker. CONCLUSION： The low molecular weight heparin-superoxide dismutase conjugate may provide neuroprotection through astrocytic activation at the super-early stage of cerebral ischemia and reperfusion.展开更多
BACKGROUND： Several studies have demonstrated that low molecular weight heparin-superoxide dismutase （LMWH-SOD） conjugate may exhibit good neuroprotective effects on cerebral ischemia/reperfusion injury though anti...BACKGROUND： Several studies have demonstrated that low molecular weight heparin-superoxide dismutase （LMWH-SOD） conjugate may exhibit good neuroprotective effects on cerebral ischemia/reperfusion injury though anticoagulation, decreasing blood viscosity, having anti-inflammatory activity, and scavenging oxygen free radicals. OBJECTIVE： To investigate the intervention effects of LMWH-SOD conjugate on serum levels of nitric oxide （NO）, glutathione peroxidase （GSH-Px）, and myeloperoxidase （MPO） following cerebral ischemia/reperfusion injury. DESIGN, TIME AND SETTING： A randomized, controlled, and neurobiochemical experiment was performed at the Institute of Biochemical Pharmacy, School of Pharmaceutical Sciences, Shandong University between April and July 2004. MATERIALS： A total of 60 Mongolian gerbils of either gender were included in this study. Total cerebral ischemia/reperfusion injury was induced in 50 gerbils by occluding bilateral common carotid arteries. The remaining 10 gerbils received a sham-operation （sham-operated group）. Kits of SOD, NO, and MPO were sourced from Nanjing Jiancheng Bioengineering Institute, China. LMWH, SOD, and LMWH-SOD conjugates were provided by Institute of Biochemistry and Biotechnique, Shandong University, China. METHODS： Fifty successful gerbil models of total cerebral ischemia/reperfusion injury were evenly randomized to five groups： physiological saline, LMWH-SOD, SOD, LMWH ＋ SOD, and LMWH. At 2 minutes prior to ischemia, 0.5 mL/65 g physiological saline, 20 000 U/kg LMWH-SOD conjugate, 20 000 U/kg SOD, a mixture of SOD （20 000 U/kg） and LMWH （LMWH dose calculated according to weight ratio, LMWH： SOD = 23.6：51）, and LMWH （dose as in the LMWH ＋ SOD group） were administered through the femoral artery in each above-mentioned group, respectively. MAIN OUTCOME MEASURES： Serum levels of NO, MPO, and GSH-Px. RESULTS： Compared with 10 sham-operated gerbils, the cerebral ischemia/reperfusion injury gerbils exhibited decreased serum levels of GSH-Px and increased serum levels of NO and MPO （P 〈 0.01）. The serum level of GSH-Px was significantly upregulated in all groups, in particular in the LMWH-SOD group （P 〈 0.01）, compared with the physiological saline group （P 〈 0.05-0.01）. Following medical treatment, serum levels of NO and MPO were significantly downregulated in all groups, in particular in the LMWH-SOD group （P 〈 0.01）. Serum levels of GSH-Px, NO, and MPO in the LMWH-SOD group were close to those in the sham-operated group （P 〉 0.05）. CONCLUSION： In cerebral ischemia/reperfusion injury, LMWH-SOD conjugate exhibits stronger neuroprotective effects on free radical scavenging, inflammation inhibition, and cytotoxicity inhibition than simple or combined application of LMWH and SOD by downregulating NO and MPO levels and upregulating the GSH-Px level.展开更多
目的观察低分子肝素-超氧化物歧化酶(LMWH-SOD)对沙土鼠脑缺血再灌注脑组织肿瘤坏死因子α(TNF-α)表达的影响,探讨LMWH-SOD脑保护作用机制。方法健康沙土鼠48只,随机分为假手术组、生理盐水组、低分子肝素(LMWH)组、超氧化物歧化酶(SOD...目的观察低分子肝素-超氧化物歧化酶(LMWH-SOD)对沙土鼠脑缺血再灌注脑组织肿瘤坏死因子α(TNF-α)表达的影响,探讨LMWH-SOD脑保护作用机制。方法健康沙土鼠48只,随机分为假手术组、生理盐水组、低分子肝素(LMWH)组、超氧化物歧化酶(SOD)组、LMWH与SOD联合(LMWH+SOD)治疗组和LMWH-SOD组。建立沙土鼠全脑缺血再灌注损伤模型,采用免疫组织化学染色法检测脑缺血10 m in再灌注6 h沙土鼠脑组织内TNF-α表达的变化。结果脑缺血再灌注后脑组织内TNF-α的表达明显升高;与生理盐水组比,各用药组TNF-α阳性细胞数明显减少(P<0.01),细胞染色明显变浅;而LMWH-SOD对TNF-α表达的抑制最为显著,阳性细胞数减少最为明显,与其它用药组比较差异有统计学意义(P<0.01),细胞着色也较浅。结论LM-WH-SOD对脑缺血再灌注损伤有保护作用,其脑保护机制可能与抑制炎性细胞因子TNF-α的过度表达有关。展开更多
文摘BACKGROUND： Studies have shown that low molecular weight heparin-superoxide dismutase conjugate exhibits a remarkable neuroprotective effect. OBJECTIVE： To investigate the effect of low molecular weight heparin-superoxide dismutase conjugate on astrocytes in an interleukin-6 （IL-6） overexpressing mice following local cerebral ischemia. DESIGN, TIME AND SETTING： Randomized, cytological, controlled, animal study was performed in the Department of Physiology and Neuroscience, Neurology and Biochemistry and Molecular Biology, Medical University of South Carolina from January 2005 to March 2005. MATERIALS： Nine IL-6 transgenic mice, irrespective of gender, were randomly divided into three groups： sham-operated, model, and treatment, with three mice in each group. With exception of the sham-operated group, right middle cerebral artery occlusion was induced in the mice. Expression of glial fibrillary acidic protein, an astrocyte marker, was determined by immunohistochemistry. Low molecular weight heparin-superoxide dismutase conjugate was purchased from Biochemistry and Biotechnique Institute, Shandong University. METHODS： Two minutes prior to ischemia induction, 0.5 mL/kg saline or 20 000 U/kg low molecular weight heparin-superoxide dismutase conjugate were administrated via the femoral artery in the model group and treatment group, respectively. The sham-operated group underwent the same protocols, with the exception of occlusion and treatment. MAIN OUTCOME MEASURES： The number of glial fibrillary acidic protein-positive cells was quantified under light microscopy （x200）. RESULTS： In the sham-operated group, there were a large number of astrocytes in the IL-6 transgenic mice. However, the cell bodies were small, and the branches were few and thin. The number of astrocytes in the model group was remarkably less than the sham-operated group. Compared to the model and sham-operated groups, the number of astrocytes significantly increased, and the cell body became larger, following treatment with low molecular weight heparin-superoxide dismutase conjugate. Astrocytes exhibited hypertrophy and hyperplasia, and the processes became longer and thicker. CONCLUSION： The low molecular weight heparin-superoxide dismutase conjugate may provide neuroprotection through astrocytic activation at the super-early stage of cerebral ischemia and reperfusion.
文摘BACKGROUND： Several studies have demonstrated that low molecular weight heparin-superoxide dismutase （LMWH-SOD） conjugate may exhibit good neuroprotective effects on cerebral ischemia/reperfusion injury though anticoagulation, decreasing blood viscosity, having anti-inflammatory activity, and scavenging oxygen free radicals. OBJECTIVE： To investigate the intervention effects of LMWH-SOD conjugate on serum levels of nitric oxide （NO）, glutathione peroxidase （GSH-Px）, and myeloperoxidase （MPO） following cerebral ischemia/reperfusion injury. DESIGN, TIME AND SETTING： A randomized, controlled, and neurobiochemical experiment was performed at the Institute of Biochemical Pharmacy, School of Pharmaceutical Sciences, Shandong University between April and July 2004. MATERIALS： A total of 60 Mongolian gerbils of either gender were included in this study. Total cerebral ischemia/reperfusion injury was induced in 50 gerbils by occluding bilateral common carotid arteries. The remaining 10 gerbils received a sham-operation （sham-operated group）. Kits of SOD, NO, and MPO were sourced from Nanjing Jiancheng Bioengineering Institute, China. LMWH, SOD, and LMWH-SOD conjugates were provided by Institute of Biochemistry and Biotechnique, Shandong University, China. METHODS： Fifty successful gerbil models of total cerebral ischemia/reperfusion injury were evenly randomized to five groups： physiological saline, LMWH-SOD, SOD, LMWH ＋ SOD, and LMWH. At 2 minutes prior to ischemia, 0.5 mL/65 g physiological saline, 20 000 U/kg LMWH-SOD conjugate, 20 000 U/kg SOD, a mixture of SOD （20 000 U/kg） and LMWH （LMWH dose calculated according to weight ratio, LMWH： SOD = 23.6：51）, and LMWH （dose as in the LMWH ＋ SOD group） were administered through the femoral artery in each above-mentioned group, respectively. MAIN OUTCOME MEASURES： Serum levels of NO, MPO, and GSH-Px. RESULTS： Compared with 10 sham-operated gerbils, the cerebral ischemia/reperfusion injury gerbils exhibited decreased serum levels of GSH-Px and increased serum levels of NO and MPO （P 〈 0.01）. The serum level of GSH-Px was significantly upregulated in all groups, in particular in the LMWH-SOD group （P 〈 0.01）, compared with the physiological saline group （P 〈 0.05-0.01）. Following medical treatment, serum levels of NO and MPO were significantly downregulated in all groups, in particular in the LMWH-SOD group （P 〈 0.01）. Serum levels of GSH-Px, NO, and MPO in the LMWH-SOD group were close to those in the sham-operated group （P 〉 0.05）. CONCLUSION： In cerebral ischemia/reperfusion injury, LMWH-SOD conjugate exhibits stronger neuroprotective effects on free radical scavenging, inflammation inhibition, and cytotoxicity inhibition than simple or combined application of LMWH and SOD by downregulating NO and MPO levels and upregulating the GSH-Px level.
文摘目的观察低分子肝素-超氧化物歧化酶(LMWH-SOD)对沙土鼠脑缺血再灌注脑组织肿瘤坏死因子α(TNF-α)表达的影响,探讨LMWH-SOD脑保护作用机制。方法健康沙土鼠48只,随机分为假手术组、生理盐水组、低分子肝素(LMWH)组、超氧化物歧化酶(SOD)组、LMWH与SOD联合(LMWH+SOD)治疗组和LMWH-SOD组。建立沙土鼠全脑缺血再灌注损伤模型,采用免疫组织化学染色法检测脑缺血10 m in再灌注6 h沙土鼠脑组织内TNF-α表达的变化。结果脑缺血再灌注后脑组织内TNF-α的表达明显升高;与生理盐水组比,各用药组TNF-α阳性细胞数明显减少(P<0.01),细胞染色明显变浅;而LMWH-SOD对TNF-α表达的抑制最为显著,阳性细胞数减少最为明显,与其它用药组比较差异有统计学意义(P<0.01),细胞着色也较浅。结论LM-WH-SOD对脑缺血再灌注损伤有保护作用,其脑保护机制可能与抑制炎性细胞因子TNF-α的过度表达有关。
