目的研究依达拉奉影响肝脏缺血再灌注过程中TNF-α的表达情况，探讨依达拉奉对肝脏缺血再灌注损伤的逆转作用。 方法将80只Wistar大鼠编号，根据计算机产生随机数字，前40为一组，后40为一组，分为实验组和对照组2组，建立常温下部分肝缺血再灌注损伤动物模型。 在肝脏缺血再灌注损伤开始前1 h和开始时对实验组大鼠给予依达拉奉注射液10 ml，对照组则给予同等容量的生理盐水。分别于再灌注后0、1、2及4 h测定肝脏脂质过氧化物酶（LPO）和肝脏谷草转氨酶(AST) 浓度； 应用RT-PCR法检测肝组织TNF-α mRNA含量，并测定肝组织和血清中TNF-α水平； 应用TUNEL染色法检测缺血肝组织的细胞凋亡情况。结果再灌注后1、2及4 h，实验组大鼠肝脏LPO及AST浓度均明显低于对照组（Plt;0.001）； 实验组再灌注后1 h时肝组织TNF-α mRNA表达量、肝组织和血清TNF-α含量均明显升高且达峰值，但均明显低于对照组（Plt;0.05）； 再灌注后各时相实验组肝细胞凋亡率明显升高，但均明显低于对照组（Plt;0.05）。 结论依达拉奉能抑制氧化应激反应，从而降低肝缺血再灌注损伤； 并显著减少炎性细胞因子TNF-α的产生，抑制炎性反应的发生，减少肝细胞的凋亡。
Objective To observe the influence of edaravone perfusion via the pulmonary artery on postoperative lung tissue and lung function during pulmonary ischemia in deep hypothermic circulatory arrest （DHCA）， and explore its possible mechanism. Methods A total of 24 healthy New Zealand white big-ear rabbits were randomly divided into three groups： （1） control group： DHCA model under cardiopulmonary bypass （CPB） was established； （2）low potassium dextran （LPD）group： LPD solution perfusion via the pulmonary artery after the establishment of DHCA； （3）edaravone group：LPD solution containing edaravone （5 mg/kg） perfusion via the pulmonary artery after the establishment of DHCA. Oxygenation index and lung compliance were observed at the time of baseline condition， recovery of ventilation， 1 hour and 2 hours after recovery of ventilation， and postoperative lung function of the three groups were compared. Malondialdehyde （MDA） and superoxide dismutase （SOD） in pulmonary venous blood were measured. All the rabbits were sacrificed after the operation. HE staining and immunohistochemistry were performed on the lung tissues to investigate lung structure changes and inflammatory reaction. Transmission electron microscopy was used to compare ultrastructural changes of lung.Results There were no statistical difference in oxygenation index， lung compliance， MDA and SOD among the 3 groups under the baseline condition （P＞0.05）. After recovery of ventilation， oxygenation index and lung compliance deteriorated to varying degrees in all 3 groups. Oxygenation index and lung compliance of the control group and LPD group at the time of recovery of ventilation， 1 hour and 2 hours after recovery of ventilation were significantly lower than those of edaravone group （oxygenation index：recovery of ventilation and in control group and edaravone group: 198.25±11.02 mm Hg vs. 244.87±13.05 mm Hg；lung compliance：one hour after recovery ventilation in control group and edaravone group：45.88±1.64 ml/cm H2O vs. 59.75±2.38 ml/cm H2O；P＜0.05）. After CPB removal， MDA levels were increased to varying degrees in all 3 groups. MDA levels of the control group and LPD group at the time of CPB removal， 1 hour and 2 hours after CPB removal were significantly higher than those of edaravone group （P＜0.05）. After CPB removal， SOD levels were decreased to varying degrees in all 3 groups. SOD levels of the control group and LPD group at the time of CPB removal， 1 hour and 2 hours after CPB removal were significantly lower than those of edaravone group （P＜0.05）. HE staining showed clear lung structure， less red blood cell leakage， less inflammatory cell infiltration， and less alveolar fluid accumulation in the edaravone group. Immunohistochemistry showed that integral light density of interleukin 6 （IL-6）in edaravone group was significantly lower than those of the LPD group and control group （14.44±1.75 vs. 20.18±2.22， P＜0.05）. Transmission electron microscopy showed integral basement membrane structure， clear blood gas barrier structure， significantly larger number of type II epithelial cells， abundant but not swollen mitochondria and lamellar bodies in the cytoplasm in the edaravone group， which were destroyed in varying degrees in the LPD group and control group. Conclusion Pulmonary artery perfusion of protective solution in low temperature can significantly reduce lung injury induced by DHCA and CPB. Protective solution containing edaravone in low temperature can better decrease lung injury and protect oxygenation.
Objective To evaluate the effectiveness and safety of edaravone combined with Xingnaojing injection in the treatment of adult acute cerebral infarction. Methods Databases including PubMed, EMbase, The Cochrane Library, CBM, CNKI, VIP and WanFang Data were searched from inception to March 2012 to identify the randomized controlled trials (RCTs) on edaravone combined with Xingnaojing injection for adult acute cerebral infarction. Two reviewers independently selected the literature, extracted the data and assessed the methodological quality of the included RCTs, and then meta-analysis was performed using RevMan 5.0 software. Results A total of 9 RCTs involving 1 098 patients were included. The results of meta-analyses showed: a) The edaravone combined with Xingnaojing injection group was superior to the Xingnaojing injection group with significant differences in the effective rate (OR=3.43, 95%CI 2.44 to 4.82, Plt;0.000 01), significantly-effective rate (OR=2.33, 95%CI 1.78 to 3.05, Plt;0.000 01), mortality (OR=0.38, 95%CI 0.15 to 0.95, P=0.04), ESS score after treatment (7 days after treatment: SMD=–0.48, 95%CI –0.80 to –0.17, P=0.003; 14 days after treatment: SMD=–0.89, 95%CI –1.17 to –0.62, Plt;0.000 01; 1 month after treatment: SMD=–0.89, 95%CI –1.20 to –0.59, Plt;0.000 01) and NDS score after treatment (7 days after treatment: MD=10.42, 95%CI 4.78 to 16.05, P=0.000 3; 14 days after treatment: MD=13.82, 95%CI 12.86 to 14.79, Plt;0.000 01; 21 days after treatment: MD=10.33, 95%CI 4.43 to 16.23, P=0.000 6); and b) The edaravone + Xingnaojing injection + conventional therapy group was superior to the conventional therapy group with significant differences in the effective rate (OR=3.03, 95%CI 1.36 to 6.73, P=0.006), significantly-effective rate (OR=2.86, 95%CI 1.50 to 5.44, P=0.001) and ESS score after treatment (7 days after treatment: MD=–6.26, 95%CI –8.49 to –4.03, Plt;0.000 01; 14 days after treatment: MD=–6.43, 95%CI –8.73 to –4.13, Plt;0.000 01). Conclusion Current evidence shows edaravone combined with Xingnaojing injection is obviously superior to either Xingnaojing injection or conventional therapy for adult acute cerebral infarction. But this conclusion still needs to be further proved by more high-quality and large-scale RCTs because of the low quality of the included studies.
ObjectiveTo investigate the effects and clinical significance of edaravone on serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1) in elderly patients with obstructive sleep apnea hypopnea syndrome (OSAHS).MethodsA total of 90 elderly patients with moderate to severe OSAHS confirmed by polysomnography were recruited from North China University of Science and Technology Affiliated Hospital in February 2016 to October 2017. According to random number table method the OSAHS patients were randomly divided into group A (n=30), group B (n=30) and group C (n=30). Group A received continuous positive airway pressure treatment for six months, group B received edaravone therapy and continuous positive airway pressure treatment for six months, and group C only received edaravone therapy for six months. The changes of serum TNF-α, IL-6 and ICAM-1 were detected by enzyme-linked immunosorbent assay before and after treatment.ResultsThe differences of serum TNF-α, IL-6 and ICAM-1 before treatment in the three groups were not statistically significant (P>0.05). Compared with before treatment, the levels of serum TNF-α, IL-6 and ICAM-1 decreased in the three groups (P<0.05). After six months of treatment, the levels of serum TNF-α, IL-6 and ICAM-1 decreased in group A and group B compared with group C (P<0.05), and decreased significantly in group B compared with group A (P<0.05).ConclusionEdaravone can inhibit the expressions of serum TNF-α, IL-6 and ICAM-1 in elderly patients with moderate to severe OSAHS, and thereby reduce vascular endothelial dysfunction and injury.
目的:观察依达拉奉联合高压氧治疗脑梗死的疗效。方法:50例脑梗死随机分成2组，对照组25例采用依达拉奉治疗30 mg，静脉滴注2次/d，疗程14 d，观察组采用依达拉奉治疗的同时给予高压氧治疗，14 d后评定疗效。结果:观察组和对照组的有效率分别是96%和88%，对照组与观察组比较Plt;0.05，差异有统计学意义。结论:依达拉奉联合高压氧治疗脑梗死是一种更有效的治疗方法，值得推广。
ObjectiveTo investigate the expression of C/EBP homologous protein (CHOP) in lung tissue of chronic intermittent hypoxia rats, and explore the intervention effect of edaravone and its possible mechanism.MethodsA total of 120 adult male Wistar rats were randomly divided into three groups: a normal control group (UC group), a chronic intermittent hypoxia group (CIH group), an edaravone intervention group (NE group), and a normal saline group (NS group). The above four groups were also randomly divided into five time subgroups of 3 days, 7 days, 14 days, 21 days and 28 days, respectively, with 6 rats in each time subgroup. The histopathological changes of lung tissue were observed by hematoxylin-eosin (HE) staining and the expression of CHOP in lung tissue was detected by immunohistochemical method.ResultsHE staining results showed that there was no obvious pathological change in UC group. The epithelial cells of lung tissue in CIH group showed edema, hyperemia, widening of alveolar septum and inflammatory cell infiltration. The pathological injury was more serious with the prolongation of intermittent hypoxia time. There were also pathological changes in NE group, but the degree of lung tissue injury was significantly lower than that in CIH group. The results of immunohistochemistry showed that the expression of CHOP in CIH group was significantly higher than that in UC group. The expression of CHOP in NE group was higher than that in UC group, but it was still significantly lower than that in CIH group.ConclusionsThe expression of CHOP protein in lung tissue of chronic intermittent hypoxic rats is enhanced and the high expression of CHOP protein plays a certain role in the lung injury of chronic intermittent hypoxia rats complicated with lung injury. Edaravone may protect lung tissue from chronic intermittent hypoxia by inhibiting the expression of CHOP.
Objective To observe the short-term effect and safety of hyperbaric oxygen combined with edaravone and ozagrel sodium in treating progressive cerebral infarction. Methods A total of 65 in-patients with acute progressive cerebral infarction were randomly divided into two groups: 33 in-patients in the trial group were treated by hyperbaric oxygen combined with edaravone and ozagrel sodium, while the other 32 in-patients in the control group were treated by edaravone and ozagrel sodium. The course of treatment was 14 days. The following indications were assessed before and after the treatment respectively: the national institutes of health stroke scale (NIHSS), activities of daily living (ADL), and clinical effects. Results This study showed that the scores of both ADL and NIHSS in the trial group were higher than those in the control group, with significant differences (Plt;0.05). The clinical effective rate of the trial group was 90.91% which was obviously higher than the control group with a significant difference (P=0.028). There were no obvious adverse reactions in both groups. Conclusion Hyperbaric oxygen combined with both edaravone and ozagrel sodium is notable in short-term effect and safe, thus it is worth being popularized in clinical treatment.
Objective To explore the potential protective effect in vivo of Edaravone, a free radical scavenger on model of acute lung injury in rats with sepsis. Methods Twenty-four male Wistar rats were randomly divided into three groups, ie. a control group( NS group) , a model group( LPS group) , a Edaravone treatment group( ED group) . ALI was induced by injecting LPS intravenously( 10 mg/ kg) in the LPS group and the ED group. Meanwhile the ED group was intravenously injected with Edaravone( 3 mg/ kg) . The NS group was injected with normal saline as control. The lung tissue samples were collected at 6 h after intravenous injection. The wet / dry ( W/D) weight ratio of lung tissue was measured. The levels of myeloperoxidase ( MPO) , malondialdehyde ( MDA ) and superoxide dismutase ( SOD) in lung tissue homogenate were assayed. The pathological changes and expression of nuclear factor-kappa B( NF-κB) in lung tissue were also studied. Results Compared with the NS group, The W/D, pathological scores, NF-κB expression, MPO and MDA levels in the LPS group were significantly higher( all P lt; 0. 01) , and the level of SOD was apparently lower( P lt; 0. 01) . The W/D, pathological scores, NF-κB expression, MPO and MDA levels in the ED group were significantly lower than those in the LPS group( all P lt; 0. 01) and higher than those in the NS group( all P lt; 0. 01) . And the level of SOD in lung tissue of the ED group was higher than that in the LPS group and lower than that in the NS group ( P lt; 0. 01) . Conclusions Edaravone has protective effect on ALI rat model. The mechanismmay be related to its ability of clearing the reactive oxygen species, inhibiting the activation of the signal pathway of NF-κB and inflammatory cascade.
Objective To investigate the impact of edaravone on serum reactive oxygen species during the perioperative period of off-pump coronary artery bypass grafting （OPCAB）. Methods A total of 40 patients who underwent selective OPCAB in the First Hospital of Hebei Medical University between June 2011 and November 2012 were prospectively enrolled in this study. All the patients were randomly divided into a trial group and a control group by a random digitaltable method with 20 patients in each group. There were 13 males and 7 females in the trial group with their age of 40-67（51.8±11.5） years， and 9 males and 11 females in the control group with their age of 42-70 （53.5±13.1） years. Afteranesthesia induction， patients in the trial group received continuous intravenous infusion of edaravone 60 mg （diluted in 100 ml saline）， while patients in the control group received continuous intravenous infusion of saline 100 ml， both of whichwere finished within 30 minutes. Venous blood samples were taken 24 hours preoperatively （T1）， 1 hour after skin incision（T2）， at the end of the surgery （T3） and 24 hours postoperatively （T4） to examine the concentration of superoxide dismutase（SOD） and malondialdehyde （MDA）. The data of the two groups were compared. Results All the patients successfully underwent their surgery and were included in the analysis. At the T2， T3 and T4 time point， SOD concentration was 80.3±21.3 U/ml， 78.5±17.4 U/ml and 81.4±17.5 U/ml， and MDA concentration was 10.2±1.8 nmol/ml， 11.3±1.9 nmol/ml，14.8±2.1 nmol/ml respectively in the control group；SOD concentration was 92.8±18.4 U/ml，90.0±18.1 U/ml，and 88.7±18.7 U/ml，and MDA concentration was 7.2±1.7 nmol/ml，8.2±1.2 nmol/ml，10.2±1.3 nmol/ml respectively in the trial group. At each above time point， SOD activity was significantly higher in the trial group than the control group （F=2.90，P=0.003；F=2.80，P=0.003；F=2.80，P=0.001）， and MDA concentration was significantly lower in the trial group than the control group （F=2.79，P=0.001；F=2.80，P=0.001；F=2.90，P=0.000）. Conclusion Edaravone can decrease serum reactive oxygen species caused by OPCAB and reduce myocardial injury.
Objective To study the effects of edaravone on the lung injury of severe acute pancreatitis （SAP） in rats. Methods Thirty-six SD rats were randomly divided into three groups: normal control group, model group and edaravone group, and SAP was induced by intraductal administration of 5% sodium taurocholate. Edaravone was given in edaravone group, while normal saline was given in normal control group and model group. After operation 6 h rats were executed, and dry/wet weight (D/W) ratio of lung was counted, and malondialdehyde (MDA) content, superoxide dismutase (SOD) activity in serum and lung were detected, respectively. In addition, the levels of tumor necrosis factor-α (TNF-α), interleukin-1, -6 (IL-1, -6) of serum were detected.Results The MDA contentof serum and lung and the levels of TNF-α, IL-1, IL-6 in model group were markedly higher than those in normal control group and edaravone group, but D/W ratio of lung, SOD activity of serum and lung were significantly lower (Plt;0.05). Conclusion Edaravone can alleviate lung injury of rats caused by SAP.