Local and systemic effects of adrenomedullin after intestinal ischemia reperfusion

Adrenomedullin (AM) is a peptide proven to increase cellular tolerance to hypoxia and oxidative stresss and contribute angiogenesis. Despite its known therapeutic effects on myocardial, renal or spinal ischemic reperfusion injuries, its local and systemic effects on intestinal ischemic reperfusion injury still remain unknown. This study aims to demonstrate the local and systemic effects of AM on Intestinal Ischemic Reperfusion Injury (I-IRI) demonstrated in rats. Thirty male rats were randomly allocated to five groups: Control, Adrenomedullin (AM), Intestinal Ischemic Reperfusion Injury (I-IRI), Adrenomedullin and Intestinal Ischemic Reperfusion Injury (AM+I-IRI), and Intestinal Ischemic Reperfusion Injury and Adrenomedullin (I-IRI+AM). Blood and tissue samples were obtained for biochemical and histopathological evaluation. The results were expressed as mean±SEM and, P <0.05 was considered statistically significant. The levels of inflammatory cytokines were found to be elevated in I-IRI group and depleted in I-IRI+AM group. The biochemical and histopathological markers of injuries at the intestine and remote organs were found to be recuperated when the AM applied before the reperfusion phase. Results of this study demonstrated that the therapeutic drug adrenomedullin (AM) could reverse the intestinal and remote organ injuries related to intestinal ischemic reperfusion injury (I-IRI). These effects might be related to the antioxidant, anti-inflammatory, and anti-apoptotic activities of AM.

Role of fibrinogen in the attenuation of ischemia reperfusion and remote ischemic preconditioning / El papel del fibrinógeno en la atenuación de la isquemia-reperfusión y el preacondicionamiento isquémico remoto

Abstract Background: Ischemic reperfusion injury (IRI) is a common hazard involved in many human diseases, such as cerebral stroke, myocardial infarction, solid organ transplant dysfunction or failure, and vascular diseases. Understanding the molecular bases of this injury is essential for the prevention and control of these life-threatening conditions. Ischemic and remote ischemic preconditioning techniques (IPC and RIPC, respectively) have gained increasing importance in the clinical practice to protect against the IRI; however, the exact mechanisms of these techniques are not fully understood, which renders their clinical application query. Possible effectors: Nitric oxide (NO) has been reported by multiple studies to be an important mediator of the protective effects of those techniques. While the physiological concentrations of NO and fibrinogen (FB) are known to antagonize each other, the circulating levels of both effectors increase in response to RIPC. Hypothesis: While NO has potential anti-inflammatory effects, non-soluble fibrinogen (sFB) shows pro- inflammatory effects. However, the sFB may have the potential to act synergistically rather than antagonistically with NO toward the attenuation of the IRI. Conclusion: While increased FB is considered a risk factor for cardiovascular and inflammatory conditions that is also able to decrease the efflux of NO, and increase the NO oxidative metabolits and S- nitroglutathione, the increased sFB during the acute phase reaction might have other protective aspects that should be carefully investigated.

Resumen Antecedentes: La lesión por isquemia-reperfusión (LIR) es un riesgo común involucrado en muchas enfermedades humanas tales como derrame cerebral, infarto del miocardio, disfunción o falla de trasplante de órgano sólido, y enfermedades vasculares. Una comprensión de la base molecular de esta lesión es fundamental para la prevención y el control de estas enfermedades potencialmente mortales. Las técnicas de preacondicionamiento isquémico y preacondicionamiento isquémico remoto (PIR) han cobrado una creciente importancia en la práctica clínica para la protección contra la LIR, sin embargo, los mecanismos precisos de estas técnicas no se entienden plenamente, lo cual pone en duda su aplicación clínica. Posibles efectores: El óxido nítrico (ON) ha sido reportado por varios estudios como un importante mediador de los efectos protectores de estas técnicas. Si bien se sabe que las concentraciones fisiológicas del ON y fibrinógeno son antagónicas, los niveles circulantes de ambos efectores aumentan en respuesta al PIR. Hipótesis: Aunque el ON tiene posibles efectos anti-inflamatorios, el fibrinógeno insoluble muestra efectos proinflamatorios. Sin embargo, el fibrinógeno soluble puede tener el potencial de actuar de manera sinérgica en lugar de antagónica con el ON hacia la atenuación de la LIR. Conclusión: Aunque el fibrinógeno elevado se considera un factor de riesgo para las enfermedades cardiovasculares e inflamatorias, que también puede disminuir la descarga de ON y aumentar los niveles de metabolitos oxidantes del ON y de S-nitrosoglutatión, el aumento de fibrinógeno soluble durante la reacción de fase aguda puede tener otros aspectos protectores que deben ser cuidadosamente investigados.

Research status and application prospect of hemoglobin-based oxygen carriers in organ transplantation / 中国输血杂志

Hemoglobin-based oxygen carriers(HBOCs) is a category of artificial blood substitute with efficient oxygen carrying and delivery functions. Due to the outstanding oxygen-carrying properties of HBOCs, the studies of expanding its clinical applications are undergoing rapidly. Studies have shown the efficacy of HBOCs in organ transplantation as machine perfusion solution in maintaining the organ metabolism or meliorating the margin donor organ quality with promising perspectives. This article aims to review the application status and prospect of HBOCs in organ transplantation in recent years.

Ethanolic Extract of Centella asiatica Ameliorates Kidney Ischemia/reperfusion Injury Through Inhibition of Inflammatory Process

@#Introduction: Kidney ischemic-reperfusion injury (IRI) is the main cause of acute kidney injury (AKI) which leads to the inflammation epithelial apoptosis and interstitial fibrosis as the chronic consequenses. Centella asiatica (CeA) has been known to have various pharmacological effects such as, anti-inflammatory, antioxidant, anti-fibrosis, and, anti-apoptosis. We aimed to elucidate the role of CeA in inhibiting kidney injury and infammatory mediators due to kidney IRI. Methods: Kidney IRI were performed with bilateral renal pedicles clamping in Swiss background mice (3 months-old, 30-40 grams) for 30 minutes (IR group, n=6), then terminated at day 7 after operation. At the next day, the mice that have been underwent bilateral kidney IRI were administered per-orally with ethanolic extract of CeA (210 mg/kg of BW, CeA1 group, n=6, and 420 mg/kg of BW, CeA2 group, n=6). The Sham Operation (SO group, n=6) was used as control. At the day 7 after the surgery, the mice were sacrificed and the kidneys were harvested. The kidney was used to assess tubular injury, interstitial fibrosis, and macrophage number, and another kidney was used to assess the mRNA expression of TLR4. Data were quantified using SPSS 22. Results: Kidney IRI produced significantly higher tubular injury, interstitial fibrosis and macrophage number (p<0.05) compared to SO with upregulating TLR4 mRNA expression (p<0.05). CeA treatment attenuated the tubular injury, interstitial fibrosis, macrophage number, and TLR4 mRNA expression which obviously shown in higher-dose of CeA (p<0.05). Conclusion: CeA ameliorates tubular injury, kidney fibrosis, and inflammatory mediators due to kidney IRI.

Protective effect of combined melatonin and alpha-tocopherol administration in spinal cord ischemia-reperfusion injury in rat / Efecto protector de la administración combinada de melatonina y alfa-tocoferol en la lesión por isquemia-reperfusión de la médula espinal en ratas

Oxidative stress and inflammation are the key players in the development of motor dysfunction post-spinal cord ischemic reperfusion injury (SC-IRI). This study investigated the protective effect of concomitant pre-administration of melatonin and alpha-tocopherol on the early complications (after 48 hours) of spinal cord IRI injury in rats. Melatonin or α-tocopherol were preadministered either individually or in combination for 2 weeks, then rats were exposed SC-IRI. Neurological examinations of the hind limbs and various biochemical markers of oxidative stress and inflammation in the SC tissue were assessed. Solely pre-administration of either melanin or α-tocopherol significantly but partially improved motor and sensory function of the hind limbs mediated by partial decreases in SC levels of MDA, AOPP and PGE2 levels and activities of SOD, partial significant decreases in plasma levels of total nitrate/nitrite and significant increases in AC activity of GSH-Px. However, combination therapy of both drugs resulted in the maximum improvements in all neurological assessments tested and biochemical endpoints. In conclusion, by their synergistic antioxidant and antiinflammatory actions, the combination therapy of melatonin and α-tocopherol alleviates SC-IRI induced paraplegia.

El estrés oxidativo y la inflamación son claves en el desarrollo de la disfunción motora posterior a lesión isquémica de la médula espinal (SC-IRI). Este estudio investigó acerca del efecto protector de la administración previa concomitante de la melatonina y alfa-tocoferol en las complicaciones tempranas (después de 48 horas) de la lesión de IRI de la médula espinal en ratas. La melatonina o el α-tocoferol se administraron individualmente o en combinación durante 2 semanas, luego las ratas fueron expuestas a SC-IRI. Se evaluaron los exámenes neurológicos de las miembros pélvicos y diversos marcadores bioquímicos de estrés oxidativo e inflamación en el tejido subcutáneo. Solo la administración previa de melatonina o α-tocoferol mejoró parcial y significativamente la función motora y sensorial de los miembros pélvicos mediadas por disminuciones parciales en los niveles de SC de los niveles de MDA, AOPP y PGE2 y las actividades de la SOD, disminuciones significativas parciales en los niveles plasmáticos del total nitrato / nitrito y aumentos significativos en la actividad de AC de GSH-Px. Sin embargo, se observaron los mejores resultados durante la combinación de ambos fármacos en todas las evaluaciones neurológicas y en los puntos finales bioquímicos. En conclusión, debido a sus acciones antioxidantes y antiinflamatorias sinérgicas, la terapia de melatonina y α-tocoferol alivia la paraplejía inducida por SC-IRI.

Protective effect of icaritin on focal cerebral ischemic–reperfusion mice / 中草药·英文版

Objective: To investigate the protective effects of icaritin (ICT), one of the active ingredients in Epimedii Folium, on mouse model of cerebral ischemia-reperfusion (I/R) in vivo. Methods: ICR mice were subjected to an 1 h transient middle cerebral artery occlusion (MCAO) and followed by 24 h of reperfusion. Neurological deficits, infarct volume, brain edema and survive rate were measured, respectively. The levels of brain IL-1β TNF-α ROS and DNA-binding activity of NF-κB p65 were measured by ELISA kits. The levels of malondialdehyde (MDA) and activities of superoxide dismutase (SOD) were detected by spectrophotometry, and the release of nitric oxide (NO) were detected by Griess kit. Results: ICT markedly reduced the neurological deficit scores, brain edema, infarct volume and increased the survival rate of the cerebral I/R mice. The expression of IL-1β TNF-α NO, MDA and DNA-binding activity of NF-κB p65 were significantly inhibited by ICT, while the activity of SOD were up-regulated at the same time. Conclusion: ICT possessed significant neuroprotective effects in cerebral I/R mice, which might be related to prevent neuroinflammatory and oxidative damage.

Application of targeted temperature management in the treatment of cardiac arrest in adult patients / 中华危重病急救医学

Cardiac arrest (CA) is a fatal condition with low resuscitation rate and high mortality rate. Most of the survivors have neurological sequelae affecting their quality of life. Targeted temperature management (TTM) has been suggested by a number of studies to increase the survival rate and improve neurological outcome of CA. It is highly recommended by the International Liaison Committee on Resuscitation (ILCOR) for unconscious patients after resuscitation. In this review, we discuss the pathological mechanism of brain injury in CA and applications of TTM in adults with CA, with the aim of providing valuable information for clinical application.

Protective Effects of Duloxetine on Arrhythmia in Rats with Myocardial Ischemia Reperfusion Injury / 医学研究杂志

Objective To explore the protective effects of duloxetine on ventricular arrhythmia in rats with ischemia reperfusion injury.Methods Thirty Sprague Dawley (SD) rats were randomly divided into 3 groups:Sham group,ischemia reperfusion group (IR group),duloxetine-treated group (Dulo group).The rats in IR group were subjected to 30min-ischemia of left anterior descending artery ligation followed by 120min of reperfusion,while intraperitoneal injection of duloxetine 40mg/kg were give prior ischemia in Dulo group,and the remaining experiment protocols were same as IR group.The left anterior descending artery of rats in sham group was exposed without being clamped.Two biopotential leads ECG monitor was used to record the arrhythmia in each group,and ECG parameters were analyzed by LabChart 8 software.Triphenyltetrazolium chloride (TTC) was used for determination of infarct area.The protein expressions of Akt,extracellular regulated protein kinases (Erk),caspase-3,superoxide dismutase (SOD) 1,SOD2 and Connexin 43 (Cx 43) were measured by western blot analysis.Results As compared to IR group,the incidences of both ventricular extrasystoles and tachycardia were decreased during ischemic period (P ＜0.05),and the incidence of ventricular tachycardia was decreased with no significant changes in ventricular extrasystoles during reperfusion period in Dulo group (P ＜ 0.05).Duloxetine decreased the prolonged QTc and infraeted area during IR injury (P ＜ 0.05).Duloxetine inhibited the phosphorylation of Akt and Erk,and downregulated the protein expressions of cleaved caspase-3,cytochrome C,while upregulated SOD1,SOD2 and Cx 43 protein expression during I/R injury (P ＜ 0.05).Conclusion Duloxetine decreases the phosphorylation of Akt and Erk,inhibits oxidative stress and apoptosis,exerts anti-arrhythmogenic effects and decreases the occurrence of ventricular arrhythmia and infracted area induced by myocardial IR.

Protective Effect of Total Saponins in Stems and Leaves of Panax notoginseng on Myocardial Ischemic Reperfusion Injury in Rats / 世界科学技术-中医药现代化

Objective To explore the protective effect of saponins in stems and leaves of Panax notoginseng onmyocardial ischemic reperfusion injury in rats. Methods The rats were divided into six groups (the sham operation group, model group, DAXXK group, PNSSL 40, 80, 160 mg·kg-1 group) and continuous oral administration for 7 days. The ratmodel of myocardial ischemic reperfusion injury (MIRI) was developed by ligation of the left anterior descending coronaryartery the electrocardiogram (ECG), myocardial infarct size, staining with hematoxylin and eosin were observed. Theactivities of LDH、CK、AST、ALT in serum and SOD、GSH-Px、MDA in cardiac muscle tissue were detected by kit.Results Saponins in stems and leaves of Panax notoginseng in each dose (40, 80, 160 mg · kg-1) group significantlyreduced the myocardial infarct size and improved the ECG on ST segment, the myocardial damage was obviously reducedfrom the pathological section. Stems and leaves of Panax notoginseng in a dose of 160 mg · kg-1 lowered the serumactivities of LDH、CK and AST, contents of SOD and GSH-Px in a dose of 80 mg·kg-1 significantly lowered. Conclusions The results indicates that PNSSL have the effect against myocardial ischemic reperfusion injury and that the mechanismof pharmacological action related to the improvement of ECG changes, the stability of cell membrane, eliminate oxygenfree radicals and the reducing of inflammatory infiltration.

Effects of CNTF Antibody Block to the Bone Marrow Mesenchymal Stem Cells Transplantated by Abdominal Aortic on the Downstream Signaling Pathways STAT3/Caspase-9 in Spinal Cord Ischemic Reperfusion Injuried Rats / 昆明医科大学学报

Objective To investigate the functional recovery and the effect of CNTF antibody block to the bone marrow mesenchymal stem cells (BMSCs) transplantated by Abdominal aortic on the downstream signaling pathways STAT3/Caspase-9 in spinal cord ischemic reperfusion injury in rats.Methods Adult female SD ratswere assigned randomly to 4 groups. The neurological functional status of the animals was assessed with BBB scores, the Motor evoked potentials (MEP) and Cortical somatosensory evoked potentials (CSEP).The IHC were used to detect the the expressional changes of CNTF, then Western blot and RT-PCR were used to detect the expressional changes of STAT3、p-STAT3、CNTF and Caspase-9 in the ischemic segments of spinal cord.Results Compared with the sham group, in the SCIRI rats, the BBB scores were markedly decreased at all time points (P＜0.01), the latency and the amplitude of MEP and CSEP was longer and lower at 14 d post operation (P＜0.01), and this change was the most significant in the control group the second in the CNTF block group, and the last in the transplantation group, Resutts between each two groups were statistically significant (P＜0.05). At 7 d post operation, compared with the sham group, the immunoreactive products of CNTF were decreased in the CNTF block group (P＜0.05), but were increased (P＜0.05) in the control group and the transplantation group (P＜0.05), and results in the transplantation group were higher than in the control group (P＜0.05). At 7 d post operation, compared with the sham group, the m RNA and protein level of CNTF、STAT3、 p-STAT3 were decreased obviously in CNTF block group (P＜0.05), the levels were increased in the control group and the transplantation group (P＜0.05), and the levels in the transplantation group were higher than that in the control group (P＜0.05); but the m RNA and protein level of Caspase-9 were only decreased in the transplantation group (P＜0.05), the level was increased in the CNTF block group and the control groups (P＜0.05), and the level in the CNTF block group was more significantly increased than that in the control group (P＜0.05). At 14 d post operation, in CNTF block group, the m RNA and protein level of CNTF、STAT3、p-STAT3 were significantly higher than that in the sham group and the control group (P＜0.05), and the m RNA and protein level of caspase-9 was higher than that in the sham group (P＜0.05), but lower than that in the control group (P＜0.05), there were not statistically different in the level of each factor compared with transplantation group (P＞0.05). Conclusions BMSCs, transplanted by the abdominal aorta, can promote the expression of CNTF in the injuried spinal cord and significantly improve the hind limb function recovery by CNTF-mediated signaling pathway downstream of STAT3/Caspase-9 SCIRI in rats, but the role of BMSCs can be weakening by CNTF block that inhibited STAT3/Caspase-9 signaling pathway.

Protective Effect of Glycyrrhetinic Acid on Myocardial Ischemia/Reperfusion Injury / 中国药学杂志

OBJECTIVE: To explore the protective effect of glycyrrhetinic acid (GA) on myocardial ischemia/reperfusion injury. METHODS: Forty-eight healthy male SD rats were randomly and averagely divided into six groups: sham, control, and control with tanshinone ⅡA sodium injection, GA at low, median and high dosages. The rats were subjected to 30 min of ischemia, followed by 180 min reperfusion. The influence of GA on arrhythmic during reperfusion period was observed. At the end of reperfusion period, the concentrations of CK-MB and LDH in serum were measured with assay kits, and the myocardial infarct size was measured with colouring method. RESULTS: At the time of myocardial ischemia and reperfusion, the HR, MAP and PRI in any GA group were not significantly different compared with the control group. At the end of the reperfusion period, the myocardial infarct sizes were decreased significantly in median and high dosage GA groups compared with the control group (P < 0.05); the CK-MB concentration in serum in all the GA groups were much lower (P < 0.05); the LDH concentrations in serum were much lower in median and high dosage GA groups (P < 0.05). CONCLUSION: GA exerts protection against myocardial ischemia/reperfusion as shown by a significant reduction in infarct size and decreased concentrations of CK-MB and LDH in serum.

The protective effects of ulinastatin on brain tissue after CPR in swine / 中华急诊医学杂志

Objective To study the protective effects of ulinastatin on brain tissue from pathomorphism and the changes of serum IL-6,Ngb (neuroglobin of brain),S100B protein and superoxide dismutase (SOD) after cardiopulmonary resuscitation (CPR) in swine.Methods The CPR model of swine was made by a programmed electric stimulation given to myocardium to produce a ventricular fibrillation and then a CPR was given.A flock of 16 male healthy Beijing landraces pigs of 3-4 months old were divided in random number method into control group (n =6) and ulinastatin group (n =6),because there were 12 swine survived from ventricular fibrillation.The t-test was used for the statistical analysis.ELISA was used to detect the changes in levels of those biomarkers in serum at each interval as well as the pathomorphological changes in brain tissues were observed under the light microscope after HE staining.Results (1) Before ventricular fibrillation,there were no distinct differences in levels of various biomarkers in porcine serum between two groups.After ventricular fibrillation,serum IL-6,S100B protein and Ngb levels in both groups gradually increased as time elapsed,and the levels of those biomarkers in the control were significantly higher than those in the ulinastatin group (P ＜ 0.05).Serum SOD in both groups gradually reduced,and more distinct decline of biomarkers was found in the ulinastatin group (P ＜ 0.05).(2) HE staining showed the porcine brain tissues in control group had significant ischemia,degeneration and necrosis and the degree of those pathological changes in the ulinastatin group were significantly moderated.Conclusion The immediate administration of ulinastatin as CPR initiated can alleviate porcine brain tissue damage after ischemia/reperfusion (I/R).This showed a protective effect of ulinastatin against I/R injury on porcine brain.

Effects of necroptosis related proteins on brain ischemia/reperfusion injury in mice / 中华行为医学与脑科学杂志

Objective To explore the effect and mechanism of necroptosis related proteins in middle cerebral artery occlusion (MCAO) induced brain ischemia/reperfusion injury in mice.Methods C57BL/6 mice were used to establish the brain ischemia/reperfusion injury model induced by MCAO.MCAO mice were treated with z-VAD.fmk (zVAD,1.1 g/kg),GSK'872 (0.7 g/kg) and combined intervention of zVAD and GSK'872,and neurological defect was evaluated by mNSS while brain infarct volume was measured by TTC staining.Western blot and immunofluorescence assay were used to detect protein expression and location of RIP1,RIP3 and MLKL,respectively.Results Neurological defect and brain infarction were caused by MCAO.Compared with MCAO group,zVAD,GSK'872 and the combined intervention alleviated neurological defect and reduced brain infarct volume significantly (P＜0.05 or P＜0.01).The protein levels of RIP3 and RIP1 MLKL were increased in mice of MCAO group,while GSK'872 and the combined intervention obviously downregulated the aforementioned protein expression [RIP1 (GSK'872:0.64± 0.02 vs MCAO:1.28±0.02,P＜0.01);RIP3 (GSK'872:1.08±0.02 vs MCAO:1.45±0.02,P＜0.01);MLKL (GSK'872:0.54±0.01 vs MCAO:1.00±0.01,P＜0.01)].However,zVAD only slightly reduced protein expression of MLKL (P＜0.05) but didn't change the protein expression of RIP1 and RIP3 (P＞0.05).Conclusion RIP1,RIP3 and MLKL are involved in the execution of necroptosis and contribute to the pathological progress of brain ischemia/reperfusion injury.

Picroside Ⅱ plays a neuroprotective effect by inhibiting cyto C/caspase-9/caspase-3 signal pathway following ischemia/reperfusion injury in rats / 中国药理学通报

Aim To investigate the neuroprotective effect of picroside Ⅱ(PIC)on cyto C/caspase-9/caspase-3 signal pathway following ischemia/reperfusion(I/R)injury in rats.Methods Atractyloside(Atr)was selected as negative control,cyclosporin A(CsA)was selected as positive control,and PIC was selected as the treatment medicine.The I/R model was made by inserting a monofilament suture into internal carotid artery for 2 h,and then reperfused for 24 h.The cerebral infarction volume was detected by TTC staining,and the expression of cyto C,caspase-9 and caspase-3 were determined by immunohistochemical assay and Western blot.Results In model group,the cerebral infarct volume was obviously large;the expression of cyto C,caspase-9 and caspase-3 was increased significantly more than that in sham group(P<0.05).In PIC group,the cerebral infarct volume was significantly improved;the expression of cyto C,caspase-9 and caspase-3 was significantly decreased than that in model group(P<0.05).In Atr+PIC group,the rat infarction volume was reduced,and the expression of cyto C,caspase-9 and caspase-3 was significantly decreased than that in Atr group(P<0.05).Conclusion The mechanism of PIC inhibiting neuron apoptosis in focal cerebral I/R rats might be through down-regulating the expression of cyto C,caspase-9 and caspase-3.

Progress in Drug Treatment for Renal Ischemic Reperfusion Injury / 中国药师

Renal ischemia reperfusion injury refers to the recovery failure of renal function induced by renal perfusion after ischemia,and resulting in a series of pathophysiological reactions.At present,there are no sovereign drugs for the treatment of renal ischemia reperfusion injury.Based on the pathophysiological characteristics of renal ischemia reperfusion injury and the latest research results at home and abroad,the article reviewed the research progress in the therapeutical drugs for renal ischemia reperfusion injury,including apoptotic protease inhibitors,P-selectin antagonists and antioxidants,which could provide reference for the effective intervention with the disease.

The changes of β-arrestin 2 and microtubule-associated protein light chain 3 in renal tissue of rats with renal ischemia reperfusion injury / 中国小儿急救医学

Objective To investigate the expression of β-arrestin2 and microtubule-associated pro-tein light chain(LC)3 in renal of rat with acute renal ischemia reperfusion injury,and to analyze the relation-ship between them and renal injury. Methods Fifty-four male SD rat(3-4 weeks old) were randomly divid-ed into three groups:control group,sham group,acute ischemic reperfusion injury group. We established the acute renal ischemia reperfusion injury model through removing the right kidney and clamping the left renal for 45 minutes with noninvasive arterial clip. We obtained the kidney and blood samples respectively at 12 h, 24 h,36 h,48 h,72 h,96 h after the surgery. Expressions ofβ-arrestin2 and LC3 protein were detected by the immunohistochemistry method and Western blot method. The renal function and morphological changes were assessed. Results Compared with control group and sham group,the serum creatinine and kidney pathologi-cal grading of acute ischemia reperfusion injury group obviously rised. The kidney injury was the most serious at the 24 h after acute ischemic reperfusion injury. The expressions of β-arrestin2 and LC3 were little in the control group and sham group. However,the expressions of these two indicators were obviously higher and reached the peak at the 12 h after acute ischemia reperfusion injury. All these results suggested that the chan-ges of these two indicators were anterior to the histopathological changes. The expressions ofβ-arrestin 2 and LC3 protein were in positive correlation with the kidney injury(r=0. 821,P<0. 05;r=0. 913,P<0. 05). Conclusion In the acute renal ischemia-reperfusion injury,β-arrestin2 may be as a kind of upstream regula-tory protein involving in the kidney pathological process through the regulation of the autophagy.

Role of TAK1 mediated cell autophagy after global cerebral ischemia-reperfusion in rats / 临床麻醉学杂志

Objective To study the effects of TGFβ-activated kinase-1 (TAK1)mediated cell autophagy after global cerebral ischemia-reperfusion (IR ) in rats.Methods Seventy-two male Kunming rats were randomly divided into six groups:control group (group C),sham operation group (group S),ischemia-reperfusion group (group IR),TAK1 shRNA lentivirus group (group T),nega-tive lentivirus group (group Y)and normal saline group (group NS)(n = 12 each).The rats in groups T,Y and NS received cerebral ventricles injection of TAK1 shRNA lentivirus,negative lenti-virus and normal saline 10 μl two weeks before preparing animal model.Using thread embolism of the right middle cerebral artery occlusion (MCAO)to cause focal ischemia for 2 h and released for 24 h for reperfusion in groups IR,T,Y and NS.The common carotid arteries were separated but not liga-ted in group S,the rest of the procedure as the same as group IR.The rats of each group were evalua-ted by neurological severity scores (NSS)24 h after reperfusion,the cerebral infarct volume was measured with the method of TTC and the expression of TAK1,LC3Ⅱ/LC3Ⅰ,Beclin1 and p62 pro-tein in rat hippocampus were determined by using Western blot.Results The infarct volume and NSS in groups IR,T,Y and NS were significantly higher than those in group C (P <0.05).The infarct volume and NSS in group T were significantly lower than those in group IR (P <0.05).TAK1 pro-tein of hippocampus in groups IR,Y and NS was significantly higher than that in group C (P <0.05).TAK1 protein of hippocampus in group T were significantly lower than that in group IR (P <0.05).LC3Ⅱ/LC3 Ⅰand Beclin1 protein of hippocampus in groups IR,T,Y and NS were signifi-cantly higher than those in group C,and the p62 protein of hippocampus in groups IR,T,Y and NS was significantly lower than that in group C (P <0.05).The LC3 Ⅱ/LC3 Ⅰand Beclin1 in group T were significantly lower than those in group IR,and the p62 protein of hippocampus in group T was significantly higher than that in group C (P < 0.05 ).Conclusion TAK1 mediated cell autophagy takes part in the mechanism of brain ischemia-reperfusion injury in rats.

RIP3 expression and function in the liver of rats following ischemic postconditioning / 中国现代普通外科进展

Objective:To investigate the expression and function of RIP3 in the liver of rats following ischemic postconditioning.Methods:The model of 70％ hepatic ischemia and reperfusion was established,then a total of forty healthy adult male Sprague-Dawley(SD) rats were divided randomly into four groups,ten rats in each group:a sham-operation group (Sham group);an ischemia reperfusion injury group(IR group);an ischemic postconditioning group(IPO group);an ischemic postconditioning and necrostatin-1 group (Nec-1 group).The blood samples and liver tissues were collected.The serum levels of ALT and AST were detected,and the liver histological examination was performed.Western-bolt was used to detect the TNF-α and RIP3 levels.Results:Compared with the IR group,ALT and AST in serum were significantly declined in the IPO group (P＜0.05);The liver damage after ischemia and reperfusion was improved obviously in the IPO group compared to which in the IR group;The Suzuki's scores was increased in the IR group compared to which in the IPO group (P＜0.05);There was a low grade of TNF-α and RIP3 in the Sham group,whereas the level of TNF-α and RIP3 significantly increased in the IR and IPO and Nec-1 group(P＜0.05);Compared with the IR group,the level of RIP3 was further decreased in the IPO group (P＜0.05);Compared with the IPO group,the level of RIP3 was further decreased in the Nec-1 group (P＜0.05).Conclusion:RIP3-mediated necroptosis was involved during hepatic ischemia postconditioning,and the protective effect of ischemia postconditioning may act as reducing necroptosis by cutting down the levels of RIP3.

Inhibitory effect of ischemic postconditioning on autophagy induced by fo-cal cerebral ischemia reperfusion in rats / 中国病理生理杂志

AIM:To investigate the effect of ischemic postconditioning ( IPC) on autophagy induced by focal cerebral ischemia reperfusion ( I/R) in rats.METHODS:Healthy male SD rats were assigned randomly into sham-opera-tion (sham) group, I/R group and IPC group with 10 rats in each group.The rats in sham group were only exposed the right common , internal and external carotid artery surgically .The rats in I/R group were subjected to right middle cerebral artery occlusion (MCAO) by the modified Longa suture method for 2 h followed by 24 h of reperfusion.The rats in IPC group were subjected to MCAO for 2 h followed by reperfusion of the ipsilateral common carotid artery occlusion for 10 s for 5 episodes, and then reperfusion for 24 h.Autophagy was obeserved by transmission electron microscopy (TEM).The pro-tein levels of mammalian target of rapamycin (mTOR), p-mTOR and microtubule associated protein light chain 3 (LC3)-II in brain tissue of the rats were determined by Western blot .Pathological changes of brain tissue were observed by HE staining.RESULTS:The protein levels of mTOR and p-mTOR in IPC group were significantly higher than those in I/R group (P<0.05).The expression of LC3-II in IPC group was significantly lower than that in I/R group (P<0.01).The cerebral infarction area and brain water content in IPC group were significantly lower than those in I /R group (P<0.01). HE staining showed that neurons degeneration and necrosis in IPC group were significantly alleviated compared with I /R group.TEM observation showed that IPC revealed fewer autophagosomes , with much less severe cell damage than that in I/R group.CONCLUSION:IPC reduces brain ischemia reperfusion damage by decreasing autophagy of brain cells , which might be related to the activation of mTOR .

Inhibitory effect of ischemic postconditioning on autophagy induced by fo-cal cerebral ischemia reperfusion in rats / 中国病理生理杂志

AIM:To investigate the effect of ischemic postconditioning ( IPC) on autophagy induced by focal cerebral ischemia reperfusion ( I/R) in rats.METHODS:Healthy male SD rats were assigned randomly into sham-opera-tion (sham) group, I/R group and IPC group with 10 rats in each group.The rats in sham group were only exposed the right common , internal and external carotid artery surgically .The rats in I/R group were subjected to right middle cerebral artery occlusion (MCAO) by the modified Longa suture method for 2 h followed by 24 h of reperfusion.The rats in IPC group were subjected to MCAO for 2 h followed by reperfusion of the ipsilateral common carotid artery occlusion for 10 s for 5 episodes, and then reperfusion for 24 h.Autophagy was obeserved by transmission electron microscopy (TEM).The pro-tein levels of mammalian target of rapamycin (mTOR), p-mTOR and microtubule associated protein light chain 3 (LC3)-II in brain tissue of the rats were determined by Western blot .Pathological changes of brain tissue were observed by HE staining.RESULTS:The protein levels of mTOR and p-mTOR in IPC group were significantly higher than those in I/R group (P<0.05).The expression of LC3-II in IPC group was significantly lower than that in I/R group (P<0.01).The cerebral infarction area and brain water content in IPC group were significantly lower than those in I /R group (P<0.01). HE staining showed that neurons degeneration and necrosis in IPC group were significantly alleviated compared with I /R group.TEM observation showed that IPC revealed fewer autophagosomes , with much less severe cell damage than that in I/R group.CONCLUSION:IPC reduces brain ischemia reperfusion damage by decreasing autophagy of brain cells , which might be related to the activation of mTOR .