Role of Flavonoids in Traditional Chinese Medicine to Improve Cerebral Ischaemia-reperfusion Injury and Its Mechanism： A Review / 中国实验方剂学杂志

Cerebral ischemia-reperfusion injury （CIRI） has a very high incidence， disability， and mortality rates， which seriously affects human life and health. In recent years， modern medicine has made some progress in the diagnosis and treatment of CIRI， but there are still problems such as difficulties in postoperative rehabilitation and adverse drug reactions， and new therapeutic drugs for CIRI are urgently needed. As an important class of active ingredients in traditional Chinese medicine， flavonoids can play antioxidant， apoptosis inhibition， anti-inflammatory， and other pharmacological effects to improve brain tissue damage， which is important for improving the quality of life of CIRI patients and slowing down the aging of the social population. Numerous studies have found that flavonoids in traditional Chinese medicine can regulate cell surface receptors Toll-like receptor 4/nuclear factor-kappaB （TLR4/NF-κB）， phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， adenylate-activated protein kinase/mammalian target of rapamycin protein （AMPK/mTOR）， Ras homologous gene family member A/Rho-associated coiled-coil protein kinase （RhoA/ROCK）， nuclear factor E2-associated factor 2/Kelch-like epoxychloropropane-associated protein-1/haemoglobin oxygenase 1 （Nrf2/Keap1/ HO-1）， Notch， and other signaling pathways， so as to regulate the transcription and expression of related proteins after CIRI， alleviate brain tissue injury， and improve CIRI. This paper analyzed the relevant literature in China and abroad in recent years， reviewed the mechanism of action and related pathways of flavonoids in traditional Chinese medicine to improve CIRI， and explored the new therapeutic direction of CIRI at the metabolic level， with a view to providing a basis for the further development and application of flavonoids in traditional Chinese medicine.

Effect of Tongdu Xingshen Needling Method （通督醒神针刺法） on Expression of AMPA Receptors and Their Accessory Proteins in the Hippocampus of Rats with Learning Memory Impairment After Cerebral Ischaemia-Reperfusion / 中医杂志

ObjectiveTo explore the possible mechanism of Tongdu Xingshen needling method （通督醒神针刺法） on post-stroke cognitive impairment. MethodsSD rats were randomly divided into a normal group （n=12）， a sham surgery group （n=12）， a model group （n=12）， and a electroacupuncture group （n=13）. The rats in the model group and electroacupuncture group were subjected to the wire bolus method to establish the rats model with learning memory impairment after cerebral ischaemia-reperfusion. After successful modelling， the rats in the electroacupuncture group were given electroacupuncture interventions at “Shenting （GV 24）” and “Baihui （GV 20）” once a day for 30 minutes for 14 days. The other three groups did not receive other interventions but grasp. A 5-day localisation navigation experiment was conducted on the 9th day of intervention， and a spatial exploration experiment was conducted on the 14th day of intervention to evaluate the learning and memory abilities of the rats. After the spatial exploration experiment， hippocampal tissues were taken from each group of rats， and the changes in the volume of cerebral infarction were observed by TTC staining； the changes in the morphology of pyramidal neurons and the density of dendritic spines in the CA1 area of the hippocampus were observed by Golgi staining； protein immunoblotting was used to detect the relative protein expression of the subunits of the α-amino-3-carboxy-5-methylisoxazole-4-propionic acid （AMPA） receptor including glutamate receptor 1 （GluR1）， glutamate receptor 2 （GluR2）， glutamate receptor 3 （GluR3） and auxiliary proteins TARPγ2， TARPγ8 in hippocampal tissues of rats in each group； the real-time fluorescence quantitative PCR was used to detect GluR1， GluR2， GluR3 mRNA levels in the hippocampal tissues of rats. ResultsIn the localisation navigation experiment， compared with the normal group and sham surgery group， the escape latency and total distance of rats in the model group were significantly extended （P＜0.05） at day 1， 2， 3， 4， and 5； and the escape latency and total distance of rats in the electroacupuncture group tended to be significantly shorter than those in the model group （P＜0.05）. In the spatial exploration experiment， compared with the normal group and the sham surgery group， the number of rats crossing the platform in the model group was significantly reduced （P＜0.05）， and the number of crossings of the platform in the electroacupuncture group increased significantly （P＜0.05）. The results of TTC staining showed that the volume of cerebral infarction increased clearly in the model group compared with the sham surgery group （P＜0.05）， and apparently decreased in the electroacupuncture group compared with the model group （P＜0.05）. Golgi staining showed that the number of dendritic branches of pyramidal neurons and dendritic spines in hippocampal CA1 region significantly decreased in the model group compared with the normal group and the sham surgery group （P＜0.05）. The number of dendritic branches of pyramidal neurons and the density of dendritic spines in hippocampal CA1 region significantly increased in the electroacupuncture group compared with the model group （P＜0.05）. The protein relative expression levels of GluR1， GluR2， GluR3， TARPγ2 and TARPγ8， and the mRNA levels of GluR1， GluR2 and GluR3 in hippocampus decreased in the model group compared with the normal group and the sham surgery group （P＜0.05）. The protein relative expression levels of GluR1， GluR2， GluR3， TARPγ2 and TARPγ8， and the mRNA levels of GluR1， GluR2 and GluR3 in hippocampus increased in the electroacupuncture group compared with model group （P＜0.05）. ConclusionThe Tongdu Xingshen needling method can improve learning memory impairment after cerebral ischaemia-reperfusion， which may be related to up-regulation of the expression of AMPA receptor and their auxiliary protein TARP， and promoting the synaptic plasticity of hippocampal tissues.

The effect of lithium tetraborate as a novel cardioprotective agent after renal ischemia-reperfusion injury

Abstract Epidemiological studies suggest that acute kidney injury has certain effect on myocardial function. In this study, for the first time, we tested a boron compound namely lithium tetraborate an act as an anti-oxidant and anti-inflammatory agent in ischemia-reperfusion injury. For this, we employed an in vivo rat model with kidney ischemia reperfusion injury to evaluate cardiac injury to clarify the mechanisms of lithium tetraborate. The evaluation of cardiac injury through kidney artery occlusion and reperfusion rat model indicated that lithium tetraborate could (1) reduce oxidative stress-induced endothelial dysfunction; (2) attenuate the inflammatory response of cardiac cells; and (3) alleviate the apoptosis and necrosis of myocytes. In summary, lithium tetraborate demonstrates significant therapeutic properties that contribute to the amelioration of cardiac damage, and it could be a promising candidate for future applications in myocardial dysfunction.

Protective effect of naringin in rat model of renal ischemia reperfusion injury / Efecto protector de la naringina en modelo de rata con lesión por reperfusión de isquemia renal

ABSTRACT Objective: We aimed to research that naringin whether protects from renal ischemia/reperfusion induced renal damage in rats. Methods: Twenty-four Wistar albino female rats randomly were divided into three groups: 1) control group, in which the rats were only performed right nephrectomy; 2) a second group received right nephrectomy and left kidney ischemia (1 h) and reperfusion (24 h) group ischemia/reperfusion (I/R); 3) a third group received 50 mg/kg naringin orally once a day for two weeks before ischemia/reperfusion (I/R/N). Expression of cyclooxygenase-2 (COX-2), cytosolic phospholipase A2 (cPLA2), inducible nitric oxide synthase (iNOS), caspase-3, B-cell lymphoma-2 (Bcl-2), Bcl-2 associated x protein (Bax), serum creatinine (Cr), tumor necrosis factor α (TNF-α), interleukin 6 (IL-6) were measured by using enzyme-linked immunosorbent assay (ELISA). Results: Naringin-treated rats that performed renal ischemia/reperfusion demonstrated significant decrease in Cr, IL-6 and TNF-α levels when compared to the only renal ischemia/reperfusion performed rats. While renal ischemia/reperfusion caused a decrease of bcl-2 (1.72 ± 0.20 pg/ml) levels, while an increase of COX-2 (11882 ± 642 pg/ml), cPLA2 (2448 ± 139 pg/ml), iNOS (4331 ± 438 IU/ml), cleaved caspase-3 (7.33 ± 0.76 ng/ml) and Bax (2.33 ± 0.44 ng/ml) levels. The treatment of naringin reversed these kidney effects (7.47 ± 60.35 pg/ml; 9299 ± 327 pg/ml; 2001 ± 78 pg/ml; 3112 ± 220 IU/ml; 3.38 ± 0.54 ng/ml; 2.33 ± 0.44 ng/ml, respectively) (p <0.05). Conclusion: This study showed that naringin treatment attenuated renal damage induced by ischemia/reperfusion in rats.

RESUMEN Objetivo: Nuestro objetivo fue investigar si la naringina protege del daño en los riñones provocado por isquemia-reperfusión renal en ratas. Material y métodos: De forma aleatoria, dividimos 24 ratas albinas Wistar hembras en tres grupos: 1) grupo control, en el que solo se les realizó a las ratas una nefrectomía derecha; 2) un segundo grupo isquemia-reperfusión, con nefrectomía derecha e isquemia de riñón izquierdo (1 h) y reperfusión (24 h); 3) un tercer grupo al que se le administró 50 mg/kg de naringina por vía oral una vez al día durante dos semanas antes de la isquemia-reperfusión. Por medio de un ensayo inmunoabsorbente ligado a enzimas (ELISA), se midieron las siguientes expresiones: ciclooxigenasa-2 (COX-2), fosfolipasa citosólica A2 (cPLA2), óxido nítrico sintetasa inducible (ONSi), caspasa-3, linfoma de células B2 (Bcl-2), proteína X asociada a Bcl-2 (Bax), creatinina sérica (Cr), factor de necrosis tumoral alfa (FNT-α) e interleucina 6 (IL-6). Resultados: Las ratas tratadas con naringina por isquemia-reperfusión renal mostraron un descenso significativo en los niveles de Cr, IL-6 y FNT-α en comparación con las ratas a las que se les indujo isquemia-reperfusión renal pero que no se les suministró naringina. La isquemia-reperfusión renal provocó un descenso de los niveles de Bcl-2 (1,72 ± 0,20 pg/ml) y un ascenso en los niveles de COX-2 (11882 ± 642 pg/ml), cPLA2 (2448 ± 139 pg/ml), ONSi (4331 ± 438 UI/ml), caspasa-3 escindida (7,33 ± 0,76 ng/ml) y Bax (2,33 ± 0.,44 ng/ml). El tratamiento con naringina diminuyó estos efectos en el riñón (7,47 ± 60,35 pg/ml; 9299 ± 327 pg/ml; 2001 ± 78 pg/ml; 3112 ± 220 UI/ml; 3.38 ± 0.54 ng/ml; 2.33 ± 0,44 ng/ml, respectivamente) (p <0,05). Conclusión: En este estudio se demostró que el tratamiento con naringina atenuó el daño renal producido por isquemia-reperfusión en ratas.

The Effects of Lung Ischaemia/Reperfusion on TRPM Gene Expression

ABSTRACT Objective: Transient receptor potential melastatin (TRPM) are integral membrane proteins that have broad range of cellular functions. Roles of TRPM2, TRPM3, TRPM4 and TRPM7 among these channels are very important, and their roles in lung ischaemia/reperfusion injury have not been evaluated yet. The aim of this study is to investigate the contribution of these genes in lung ischaemia/reperfusion injury and evaluate histopathology of tissues. Methods: A total of 40 Wistar albino rats were enrolled for the study. Ischaemia was performed by the application of an atramvatic clamp to pulmonary artery. Gene expressions were determined by the semi-quantitative reverse transcription-polymerase chain reaction method. Histopatholical evaluations were held by a standard haematoxyline-eosin staining. Results: The major histopathological tissue damage was observed in ischaemia performed groups, and expression of TRPM channels was found to be obviously downregulated. Substantial changes were determined between TRPM2, TRPM3, TRPM4 and TRPM7 and lung ischaemia/reperfusion injury. In particular, expression of TRPM2 and TRPM7 was reversibly downregulated in ischaemia. Yet, the expression of TRPM3 and TRPM4 was irreversibly down-regulated after ischaemia. Conclusion: Consequently, these results indicate that TRPM family of cation channels may have significant roles in the lung ischaemia/reperfusion injury.

GDF -15 and Severity Scores in Sickle Cell Disease Patients Attending Nnamdi Azikiwe University Teaching Hospital, Nnewi, Anambra State, Nigeria

Aim:Granulocyte differentiation factor 15 (GDF15) is a growth factor andbiomarker for many disorders where Ischaemia Reperfusion Injury (IRI) is pathophysiologically relevant. Hence theneed to evaluate GDF-15 as a biomarker inSickle Cell Disease (SCD).Study Design:This is a cross sectional study.Place and Duration of Study: Department of Haematology, Nnamdi University Teaching Hospital, Nnewi, Anambra state, Nigeria, between January and December 2018.Methods:Ninety subjects were randomly recruitedwith haemoglobin (Hb) phenotypesSS (test),AS and AA (controls); numbering30,28and 32 respectively. Disease severity was determined by calculating an objective score. 5 mls of blood was collectedandused to determine Full Blood Count (FBC),haemoglobin Phenotype andGDF-15 levels(byEnzymeLinked Immunosorbent assay).Data collected was analysed using Statistical Package for Social Sciences software version 20 (SPSS Inc., IL, Chicago, USA). P< 0.05 was considered as significant.Results: GDF-15 level was found to be significantly differentin the different HB phenotypes p= 0.005 and correlated negatively with sickle cell disease severity (r= -0.307, p= 0.098). The difference betweenmedianGDF-15 levels of HBSS subjects with mild and moderate disease was statistically significant at p= 0.01.Conclusion:We hypothesize that GDF-15 maybeapotential therapeutic target for intervention against ischaemia/reperfusion inducedmicro-vascularinjury.Natural GDF-15 mimetics maybe useful in taking advantage of this potential therapeutic target.

Tao-Hong-Si-Wu Decoction promotes angiogenesis after cerebral ischaemia in rats via platelet microparticles / 中国天然药物

Platelet microparticles (PMPs) are membrane particles derived from the platelet membrane that enter into the blood circulation. We sought to explore the therapeutic effects of Tao-Hong-Si-Wu Decoction (THSWD) on angiogenesis in a rat model of cerebral ischaemia-reperfusion (I/R). The protective effect of THSWD on I/R rats was observed morphologically by immunohistochemical expression of VEGF and CD34, along with immunofluorescence results of co-expression of BrdU and vWF. Then, PMPs from different groups of rats were extracted, and cytokine array analysis was used to screen for angiogenesis associated proteins. The results showed that THSWD can promote the expression of VEGF, CD34, BrdU and vWF. Cytokine array analysis revealed the changes in the expression of 29 related angiogenic proteins in the total protein of PMPs, which involved the Notch signalling pathway. Compared with model group, the expression levels of NICD and Hes-1 in the THSWD group were significantly increased. In the context of I/R, the angiogenesis-related proteins of PMPs are different. THSWD may involve the promotion of activation of the Notch signalling pathway to achieve therapeutic effects on cerebral ischaemia.

Tourniquet-induced ischaemia-reperfusion injury: the comparison of antioxidative effects of small-dose propofol and ketamine / Lesão de isquemia-reperfusão induzida por torniquete: comparação dos efeitos antioxidantes de propofol e cetamina em doses baixas

Abstract Objectives: The aim of the present study was to investigate the preventive effects of propofol and ketamine as small dose sedation during spinal anaesthesia on tourniquet-induced ischaemia-reperfusion injury. Methods: 30 patients were randomly assigned into two groups of 15 patients. In the propofol group, sedation was performed with propofol 0.2 mg·kg-1 followed by infusion at a rate of 2 mg·kg-1·h-1. In the ketamine group, a continuous infusion of ketamine 0.5 mg·kg-1·h-1 was used until the end of surgery. Intravenous administration of midazolam was not used in any patients. Ramsay sedation scale was used for assessing the sedation level. Venous blood samples were obtained before propofol and ketamine infusion (T1), at 30 minutes (min) of tourniquet ischaemia (T2), and 5 min after tourniquet deflation (T3) for malondialdehyde (MDA) measurements. Results: No differences were noted between the groups in haemodynamic (p > 0.05) and demographic data (p > 0.05). There was no statistically significant difference between the two groups in terms of T1, T2 and T3 periods (p > 0.05). There was a statistically increase observed in MDA values respectively both in Group P and Group K between the reperfusion period (1.95 ± 0.59, 2.31 ± 0.48) and pre-ischaemia (1.41 ± 0.38, 1.54 ± 0.45), and ischaemia (1.76 ± 0.70, 1.71 ± 0.38) (µmoL-1) periods (p < 0.05). Conclusions: Small-dose propofol and ketamine has similar potential to reduce the oxidative stress caused by tourniquet-induced ischaemia-reperfusion injury in patients undergoing arthroscopic knee surgery under spinal anaesthesia.

Resumo Objetivos: O objetivo do presente estudo foi investigar os efeitos preventivos de propofol e cetamina em sedação com doses baixas durante a raquianestesia sobre lesão de isquemia-reperfusão induzida por torniquete. Métodos: 30 pacientes foram randomicamente alocados em dois grupos de 15 pacientes cada. No grupo propofol, a sedação foi feita com 0,2 mg.kg-1 de propofol seguida por infusão a uma taxa de 2 mg.kg-1.h-1. No grupo cetamina, uma infusão contínua de 0,5 mg.kg-1.h-1 de cetamina foi usada até o final da cirurgia. Midazolam intravenoso não foi administrado em nenhum dos pacientes. A Escala de Sedação de Ramsay (ESR) foi usada para avaliar o nível de sedação. Amostras de sangue venoso foram colhidas antes da administração de propofol e infusão de cetamina (T1), aos 30 minutos (min) de isquemia do torniquete (T2) e 5 min após a desinsuflação do torniquete (T3), para medir os valores de malondialdeído (MDA). Resultados: Não observamos diferenças entre os grupos em relação à hemodinâmica (p > 0,05) e dados demográficos (p > 0,05). Não houve diferença estatisticamente significativa entre os dois grupos nos períodos T1, T2 e T3 (p > 0,05). Um aumento estatisticamente significativo foi observado nos valores de MDA, respectivamente, no Grupo P e Grupo C entre os períodos de reperfusão (1,95 ± 0,59, 2,31 ± 0,48) e pré-isquemia (1,41 ± 0,38, 1,54 ± 0,45) e isquemia (1,76 ± 0,70, 1,71 ± 0,38) (µmoL-1) (p < 0,05). Conclusões: Propofol e cetamina em doses baixas apresentam potencial semelhante para reduzir o estresse oxidativo causado pela lesão de isquemia-reperfusão induzida por torniquete em pacientes submetidos à artroscopia de joelho sob raquianestesia.

Effect of Neurosteroid Modulation on Global Ischaemia-Reperfusion-Induced Cerebral Injury in Mice

The present study was designed to investigate the putative effect of neurosteroid modulation on global ischaemia-reperfusion-induced cerebral injury in mice. Bilateral carotid artery occlusion followed by reperfusion, produced a significant rise in cerebral infarct size along with impairment of grip strength and motor coordination in Swiss albino mice. Administration of carbamazepine (16 mg/kg, i.p.) before global cerebral ischaemia significantly attenuated cerebral infarct size and improved the motor performance. However, administration of indomethacin (100 mg/kg, i.p.) attenuated the neuroprotective effect of carbamazepine. Mexiletine (50 mg/kg, i.p.) did not produce significant neuroprotective effect. It may be concluded that the neuroprotective effect of carbamazepine may be due to increase in synthesis of neurosteroids perhaps by activating enzyme (3alpha HSD) as indomethacin attenuated the neuroprotective effect of carbamazepine. The sodium channel blocking effect of carbamazepine may not be involved in neuroprotection as mexiletine, a sodium channel blocker, did not produce significant neuroprotective effect.

Histological Study on Effect of Mesenchymal Stem Cell Therapy on Experimental Renal Injury Induced by Ischemia/Reperfusion in Male Albino Rat

BACKGROUND AND OBJECTIVES: Acute kidney injury (AKI) represents a major clinical problem with high mortality and limited treatment protocols. This study was planned to evaluate the therapeutic effectiveness of bone marrow-derived mesenchymal stem cells (BM-MSCs) in a rat model of ischemia/reperfusion (I/R) AKI. METHODS AND RESULTS: This study was carried out on thirty adult male albino rats. Animals were divided equally into three groups. Group I (control sham-operated group) (n=10), were subdivided equally into two subgroups; Ia and Ib. The experimental group (n=20) were all subjected to I/R injury by clamping both renal pedicles for 40 minutes. Half of the I/R animals did not receive MSC therapy (group II) [non-MSC treated group]. The other half of the I/R animals received single intravenous injection of PKH26 labelled BM-MSCs immediately after removal of the clamps and visual confirmation of reflow (group III) [MSC treated group]. Animals were sacrificed 24 hrs (subgroups IIa & IIIa) and 72 hrs (subgroups IIb & IIIb) after intervention. Serological measurements included serum urea and creatinine. Kidney specimens were processed for H&E, PAS and PCNA. Mean % of renal corpuscles with affected glomeruli, mean % of affected tubules, mean area % of PAS-positive reaction and mean area % of PCNA immunoreactivity were measured by histomorphometric studies and statistically compared. MSCs-treated group exhibited protection against renal injury serologically and histologically. CONCLUSIONS: Results of the present study suggest a potential reno-protective capacity of MSCs which could be of considerable therapeutic promise for cell-based management of clinical AKI.

Protective effect of hydroalcoholic extract of Andrographis paniculata on ischaemia-reperfusion induced myocardial injury in rats.

Background & objectives: Protecting myocardium from ischaemia-reperfusion (I-R) injury is important to reduce the complication of myocardial infarction (MI) and interventional revascularization procedures. In the present study, the cardioprotective potential of hydroalcoholic extract of Andrographis paniculata was evaluated against left anterior descending coronary artery (LADCA) ligation-induced I-R injury of myocardium in rats. Methods: MI was induced in rats by LADCA ligation for 45 min followed by reperfusion for 60 min. The rats were divided into five experimental groups viz., sham (saline treated, but LADCA was not ligated), I-R control (saline treated + I-R), benazepril (30 mg/kg + I-R), A. paniculata (200 mg/kg per se) and A. paniculata (200 mg/kg + I-R). A. paniculata was administered orally for 31 days. On day 31, rats were subjected to the I-R and cardiac function parameters were recorded. Further, rats were sacrificed and heart was excised for biochemical and histopathological studies. Results: In I-R control group, LADCA ligation resulted in significant cardiac dysfunction evidenced by reduced haemodynamic parameters; mean arterial pressure (MAP) and heart rate (HR). The left ventricular contractile function was also altered. In I-R control group, I-R caused decline in superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and reduced glutathione (GSH) as well as leakage of myocytes injury marker enzymes, creatine phosphokinase-MB (CK-MB) isoenzyme and lactate dehydrogenase (LDH), and enhanced lipid peroxidation product, malonaldialdehyde (MDA). However, rats pretreated with A. paniculata 200 mg/kg showed favourable modulation of haemodynamic and left ventricular contractile function parameters, restoration of the myocardial antioxidants and prevention of depletion of myocytes injury marker enzymes along with inhibition of lipid peroxidation. Histopathological observations confirmed the protective effects of A. paniculata. The cardioprotective effects of A. paniculata were found comparable to that of benazepril treatment. Interpretation & Conclusions: Our results showed the cardioprotective effects of A. paniculata against I-R injury likely result from the suppression of oxidative stress and preserved histoarchitecture of myofibrils along with improved haemodynamic and ventricular functions.

Protective effects of edaravone on ischaemia-reperfusion injury in rabbits with haemorrhagic shock / 中华急诊医学杂志

Objective To investigate the dynamic changes of MDA, NO, SOD and pathologic changes of the lung and kidneyduring repefusion after haemorrhagic shock in rabbits, and to study the protective effects of edaravone during thecourse.Method Totally 29 beparinized (3 mg/kg) rabbits were randomly divided into three groups:tho sham-operatedcontrol group (group C, n = 7), the haemorrhagic shock group (group I/R, n = 10), and the haemorrhagicshock group with edaravone infusion (group I/R-edaravone, n = 12). Rabbits in the latter two groups were bledfrom left arteria cmralis in 10 minutes with MAP maintained at 40 mmHg for 60 minutes, and then group I/R-edar-avone was given edaravone intravenously. After that, resuscitation began:all blood loss was replaced with normalsaline within 60 minutes with MAP at the end ≥ 70% MAP before haemorrhagic shock. Edaravone was reinjectedat 10 hours after shock.All rabbits were killed at 20 h after reperfusion.Plasma nitric oxide(NO), malonyldialde-hyde (MDA) and superoxide dismutase(SOD) in every group were measured before shock,60 minutes after shockaad 1 h, 5 h and 20 h after reperfusien. Part of the right lung and the right kidney tissues were taken from everyrabbit for pathologic examnation after sacrifice.Results There was no significant difference in MDA,NO aad SOD among three groups before shock. A higherlevel of MDA (5.35±0.29 μmol/L), NO(27.75 ±2.88 μmol/L)and lower serum concentration of SOD(194.58±14.42U/ml)could be found in group I/R during haemorrhagic shock,as compared to group C(4.44±0.59 μmol/L,25.01±4.95μmol/L,210.86±24.54U/ml,respectively,P<0.01).At 20 hours after resuscitation,MDA and NO contents continued to increase(5.69±0.24 μmol/L and 28.01±3.10 μmol/L respectively,P<0.05)while SOD contents kept decreasing(151.83±9.36 U/ml,P<0.05)in group I/R.Comparing to group I/R,group I/R-edaravone had significant lower level of MDA(3.48±0.23 μmol/L,P<0.01)and higher concentration of SOD(195.10±11.87U/ml,P<0.01).Edaravone attenuated the pathologic changes in the lung and kidney.Conclusions Edaravone could effectively protect vital organs from reperfusion injury caused by free radicals following haemorrhagic shock by reducing plasma levels of MDA,NO and increasing levels of SOD.