Role of β-Adrenergic Signal Transduction Pathway on Myocardial Ischemic Preconditioning of Rats

To study the changes in every part of the β-adrenergic signal transduction pathway and their effects on ischemic preconditioning of rat myocardium in vivo. SD rats were divided into three groups： IP group, I/R group and CON group. The IP group was further divided into PC1-, 2-, 3-, and PC1＋, 2＋, 3＋ groups according to preconditioning procedure. The rats received surgical procedure and underwent left coronary artery occlusion and reperfusion. We analyzed the infarct size by TTC staining, measured serum myocardial enzymes, studied the β-AR Bmax and Kd by radioligand binding assay of receptors, checked the activity of AC and PKA by the method of biochemistry and examined the content of cAMP by radioimmunoassay. The infarct area was much smaller in the IP group than in the I/R group （P〈0. 001）, while the enzymes were significantly higher in I/R （P〈0. 001）. The Bmax of β-AR in IP was much higher than that in I/R （P〈0. 001）, but no difference in Kd could be seen between IP and I/R groups. In IP, the activity of AC and PKA and the content of cAMP were higher than those in I/R （P〈0.05, 0. 002 and 0. 001, respectively）. In the procedure of preconditioning, the content of cAMP and the activity of PKA showed the characteristic of cyclic fluctuation. Ischemic preconditioning can protect the heart from necrosis and reduce endo-enzyme leakage. The system of β-adrenergic signal transduction pathway probably takes part in the protection effect of the IP, which might be elicited by the PKA .

Impact of hypoglycemic agents on myocardial ischemic preconditioning

Murry et al in 1986 discovered the intrinsic mechanism of profound protection called ischemic preconditioning. The complex cellular signaling cascades underlying this phenomenon remain controversial and are only partially understood. However, evidence suggests that adenosine, released during the initial ischemic insult, activates a variety of G protein-coupled agonists, such as opioids, bradykinin, and catecholamines, resulting in the activation of protein kinases, especially protein kinase C(PKC). This leads to the translocation of PKC from the cytoplasm to the sarcolemma, where it stimulates the opening of the ATP-sensitive K+ channel, which confers resistance to ischemia. It is known that a range of different hypoglycemic agents that activate the same signaling cascades at various cellular levels can interfere with protection from ischemic preconditioning. This review examines the effects of several hypoglycemic agents on myocardial ischemic preconditioning in animal studies and clinical trials.

Involvement of adenosine and standardization of aqueous extract of garlic(Allium sativum Linn.)on cardioprotective and cardiodepressant properties in ischemic preconditioning and myocardial ischemia-reperfusion induced cardiac injury

The present study investigated the effect of garlic （Allium sativum Linn.） aqueous extracts on ischemic pre- conditioning and ischemia-reperfusion induced cardiac injury, as well as adenosine involvement in ischemic pre- conditioning and garlic extract induced cardioprotection. A model of ischemia-reperfusion injury was established using Langendorff apparatus. Aqueous extract of garlic dose was standardized （0.5%, 0.4%, 0.3%, 0.2%, 0.1%, 0.07%, 0.05%, 0.03%, 0,01%）, and the 0.05% dose was found to be the most effective. Higher doses （more than 0.05%） were highly toxic, causing arrhythmia and cardiodepression, whereas the lower doses were ineffective. Garlic exaggerated the cardioprotective effect of ischemic preconditioning. The cardioprotective effect of ischemic preconditioning and garlic cardioprotection was significantly attenuated by theophylline （1,000 ~tmol/L） and 8-SPT （10 mg/kg, i.p.） and expressed by increased myocardial infarct size, increased LDH level, and reduced nitrite and adenosine levels. These findings suggest that adenosine is involved in the pharmacological and molecular mechanism of garlic induced cardioprotection and mediated by the modulation of nitric oxide.

Protective Effect of Electroacupuncture and Ischemic Preconditioning on the Circulatory Function in Pigs with Ischemia/Reperfusion Myocardial Injury

Objective: To investigate the effects of electroacupuncture and ischemic preconditioning (IPC) on circulatory function in pigs with myocardial ischemia/reperfusion injury. Method: Eighteen pigs with myocardial ischemia/reperfusion injury were randomly allocated into three groups, 6 in each. Group I was the control group, group II was the group that received IPC, and group III was that received both electroacupuncture and IPC. Blood malondialdehyde (MDA), superoxide dismutase (SOD), creatine phos-phokinase (CPK) and its isoenzyme (CK-MB), coronary artery flow and myocardial heat-shock protein (HSP) mRNA expression were detected for evaluation. Results: After treatment, the MDA content was decreased and SOD activities increased significantly in the acupuncture and IPC group compared with the control group (P<0. 05 respectively). The levels of CPK, CK-MB at 20, 60 min after reperfusion were significantly higher than those before treatment, but the levels in group III and group n were remarkably lower than those in group I . HSP70 mRNA expression was found to be increased in group II and group III at 60 min after ischemia/reperfusion compared with those in group I . Conclusion: Electroacupuncture can enhance the myocardial protection of IPC against ischemia/reperfusion injury. The.protective mechanism may be related to the improvement of antioxidation and the increased expression of HSP70 gene.

Flow cytometric analysis of circulating microvesicles derived from myocardial ischemic preconditioning and cardioprotection of ischemia/reperfusion injury in rats

Objective: To establish a flow cytometric method to detect the alteration of phenotypes and concentration of circulating microvesicles(MVs) from myocardial ischemic preconditioning(IPC) treated rats(IPC-MVs), and to investigate the effects of IPC-MVs on ischemia/reperfusion(I/R) injury in rats. Methods: Myocardial IPC was elicited by three cycles of 5-min ischemia and 5-min reperfusion of the left anterior descending(LAD) coronary artery. Platelet-free plasma(PFP) was isolated through two steps of centrifugation at room temperature from the peripheral blood, and IPC-MVs were isolated by ultracentrifugation from PFP. PFP was incubated with anti-CD61, anti-CD144, anti-CD45 and anti-Erythroid Cells, and added 1, 2 μm latex beads to calibrate and absolutely count by flow cytometry. For functional research, I/R injury was induced by 30-min ischemia and 120-min reperfusion of LAD. IPC-MVs 7 mg/kg were infused via the femoral vein in myocardial I/R injured rats. Mean arterial blood pressure(MAP), heart rate(HR) and ST-segment of electrocardiogram(ECG) were monitored throughout the experiment. Changes of myocardial morphology were observed after hematoxylin-eosin(HE) staining. The activity of plasma lactate dehydrogenase(LDH) was tested by Microplate Reader. Myocardial infarct size was measured by TTC staining. Results: Total IPC-MVs and different phenotypes, including platelet-derived MVs(PMVs), endothelial cell-derived MVs(EMVs), leucocyte-derived MVs(LMVs) and erythrocyte-derived MVs(RMVs) were all isolated which were identified membrane vesicles(<1 μm) with corresponding antibody positive. The numbers of PMVs, EMVs and RMVs were significantly increased in circulation of IPC treated rats(P<0.05, respectively). In addition, at the end of 120-min reperfusion in I/R injured rats, IPC-MVs markedly increased HR(P<0.01), decreased ST-segment and LDH activity(P<0.05, P<0.01). The damage of myocardium was obviously alleviated and myocardial infarct size was significantly lowered after IPC-MVs treatment(P<0.01). Conclusion: The method of flow cytometry was successfully established to detect the phenotypes and concentration alteration of IPC-MVs, including PMVs, EMVs, LMVs and RMVs. Furthermore, circulating IPC-MVs protected myocardium against I/R injury in rats.

The effect of adrenergic receptor-adenyl cyclase system on myocardial ischemic preconditioning in rats

In order to study the effects of every part of adrenergic receptor-adenyl cyclase system on ischemic preconditioning of myocardium in rats in vivo,SD rats were divided into three groups:IP group,I/R group and CON group.Rate were received surgical procedure and undergone left coronary artery occlusion and reperfusion.Hearts were extracted to analyze the infarct size by TTC staining,to measure serum myocardial enzymes,to study β-AR Bamx and Kd by radioligand binding assay of receptors(RAB),and to check the activity of AC and the content of cAMP by radioimmunoassay(RIA).The infarct area was found much smaller in IP group than I/R group(P<0.001);CK,CK-MB and LDH were found significantly higher in I/R group (P<0.001),The Bmax of β-AR in IP group were higher than in I/R group (P<0.001), No difference of Kd could be seen between IP and I/R group,In IP group,the activity of Ac and the content of cAMP were higher than I/R group(P<0.05 and 0.001,respectively).It is concluded that ischemic preconditioning can protect the hearts from necrosis and reduce endo-enzyme leakage.The system of adrenergic receptor-adenyl cyclase system probably takes part in the protection of the IP.

Role of Beclin 1-dependent Autophagy in Cardioprotection of Ischemic Preconditioning

Emerging evidence indicates that ischemic preconditioning （IPC） induces autophagy which attenuates myocardial ischemia/reperfusion （I/R） injury. However, the precise mechanisms remain com- plex and unclear. The present study was to investigate which autophagy pathway was involved in the cardioprotection induced by IPC, so that we can acquire an attractive treatment way for iscbemic heart disease. Adult male Sprague-Dawley （SD） rats were randomly divided into sham group, I/R group and IPC group. IPC was induced with three cycles of 5 min regional ischemia alternating with 5 m^n reper- fusion in a heart I/R model. Samples were taken from the center of the infracted heart and examined by using the electron microscopy, the terminal deoxynucleotidyl transferase-mediated nick end-labeling （TUNEL） method, Western blotting and co-immunoprecipitation （Co-IP）. A large number of autophagic vacuoles were observed in the cardiomyocytes oflPC group as compared with I/R group. LC3-II forma- tion, an autophagy marker, was up-regulated in IPC group as compared with FR group （P〈0.05）. Moreover, the interaction between Beclin 1 and Bcl-2 was significantly increased in IPC group as com- pared with I/R group （P〈0.01）. It was also found that IPC decreased I/R-induced apoptosis （P〈0.01）. These results suggest that IPC inhibits Beclin 1-dependent excessive autophagy in reperfusion phase and cooperates with anti-apoptosis pathway to diminish the cell death induced by the myocardial I/R injury.

Neuroprotective effect of ischemic preconditioning in focal cerebral infarction: relationship with upregulation of vascular endothelial growth factor

Neuroprotection by ischemic preconditioning has been confirmed by many studies, but the precise mechanism remains unclear. In the present study, we performed cerebral ischemic pre- conditioning in rats by simulating a transient ischemic attack twice （each a 20-minute occlusion of the middle cerebral artery） before inducing focal cerebral infarction （2 hour occlusion-reper- fusion in the same artery）. We also explored the mechanism underlying the neuroprotective effect of ischemic preconditioning. Seven days after ocdusion-reperfusion, tetrazolium chloride staining and immunohistochemistry revealed that the infarct volume was significantly smaller in the group that underwent preconditioning than in the model group. Furthermore, vascular endothelial growth factor immunoreactivity was considerably greater in the hippocampal CA3 region of preconditioned rats than model rats. Our results suggest that the protective effects of ischemic preconditioning on focal cerebral infarction are associated with upregulation of vascu- lar endothelial growth factor.

Ischemic preconditioning-induced hyperperfusion correlates with hepatoprotection after liver resection

AIM:To characterize the impact of the Pringle ma-neuver (PM) and ischemic preconditioning (IP) on total blood supply to the liver following hepatectomies. METHODS: Sixty one consecutive patients who un-derwent hepatic resection under in flow occlusion were randomized either to receive PM alone (n = 31) or IP (10 min of ischemia followed by 10 min of reperfusion) prior to PM (n = 30). Quantification of liver perfusion was measured by Doppler probes at the hepatic artery and portal vein at various time points after reperfusion of remnant livers. RESULTS: Occlusion times of 33 ± 12 min (mean ± SD) and 34 ± 14 min and the extent of resected liver tissue (2.7 segments) were similar in both groups. In controls (PM), on reperfusion of liver remnants for 15 min, portal perfusion markedly decreased by 29% while there was a slight increase of 8% in the arterial blood flow. In contrast, following IP + PM the portal vein flow remained unchanged during reperfusion and a significantly increased arterial blood flow (+56% vs baseline) was observed. In accordance with a better postischemic blood supply of the liver, hepatocellular injury, as measured by alanine aminotransferase (ALT) levels on day 1 was considerably lower in group B compared to group A (247 ± 210 U/I vs 550 ± 650 U/I, P < 0.05). Additionally, ALT levels were significantly correlated to the hepatic artery in flow.CONCLUSION: IP prevents postischemic flow reduction of the portal vein and simultaneously increases arterial perfusion, suggesting that improved hepatic macrocirculation is a protective mechanism following hepatectomy.

Outcomes and mechanisms of ischemic preconditioning in liver transplantation

BACKGROUND: Liver transplantation is so far the most effective therapeutic modality for end-stage liver diseases, but ischemia/reperfusion (I/R) injury represents a critical barrier to liver transplantation. Primary graft dysfunction and small-for-size syndrome are closely associated with I/R injury. Ischemic preconditioning (IPC) is defined as a brief period of liver ischemia followed by reperfusion, and has demonstrated protections against a prolonged I/R injury and improved the capacity of regeneration. The article aimed to review IPC literatures for the understanding of the effects of IPC on I/R injury involving in the procurement of donor liver and protective mechanisms. DATA SOURCES: A literature search of MEDLINE and Web of Science databases using 'liver transplantation', 'liver regeneration', 'hepatectomy', 'ischemia/reperfusion' and 'ischemic preconditioning' was performed, and then a large amount of related data was collected. RESULTS: The literature search provided a huge amount of evidence for the protective effects of IPC on I/R injury in liver transplantation, including reduction of blood loss in hepatectomy, intraoperative hemodynamic stability and its significant role in liver regeneration. The mechanism involves in balancing inflammatory cytokines, enhancing energy status and mitigating microcirculatory disturbance. CONCLUSION: IPC plays an essential role in hepatectomy before and after harvest of living donor liver and implantation of liver graft.

Late cardioprotection of exercise preconditioning against exhaustive exercise-induced myocardial injury by up-regulatation of connexin 43 expression in rat hearts

Objective: To investigate the expression of myocardium connexin 43(Cx43) in late exercise preconditioning(LEP) cardioprotection. Methods: Eight-week-old adult male Sprague Dawley rats were randomly assigned into four groups(n=8). Myocardial injury was judged in accordance with serum levels of c Tn and NT-pro BNP as well as hematoxylin basicfuchsin picric acid staining of myocardium. Cx43 m RNA was detected by in situ hybridization and qualified by real-time fluorescence quantitative PCR. Cx43 protein was localized by immunohistochemistry and its expression level was determined by western blotting. Results: The LEP obviously attenuated the myocardial ischemia/hypoxia injury caused by exhaustive exercise. There was no significant difference of Cx43 m RNA level between the four groups. Cx43 protein level was decreased significantly in group EE(P<0.05). However, LEP produced a significant increase in Cx43 protein level(P<0.05), and the decreased Cx43 protein level in exhaustive exercise was significantly up-regulated by LEP(P<0.05). Conclusions: LEP protects rat heart against exhaustive exercise-induced myocardial injury by up-regulating the expression of myocardial Cx43.

Protective effects of remote ischemic preconditioning in rat hindlimb on ischemia- reperfusion injury

Three cycles of remote ischemic pre-conditioning induced by temporarily occluding the bilateral femoral arteries （10 minutes） prior to 10 minutes of reperfusion were given once a day for 3 days before the animal received middle artery occlusion and reperfusion surgery. The results showed that brain infarct volume was significantly reduced after remote ischemic pre-conditioning. Scores in the forelimb placing test and the postural reflex test were significantly lower in rats having undergone remote ischemic pre-conditioning compared with those who did not receive remote ischemic pre-conditioning. Thus, neurological function was better in rats having undergone remote ischemic pre-conditioning compared with those who did not receive remote ischemic pre-conditioning. These results indicate that remote ischemic pre-conditioning in rat hindlimb exerts protective effects in ischemia-reperfusion injury.

Hepatic ischemic preconditioning increases portal vein flow in experimental liver ischemia reperfusion injury

BACKGROUND: Ischemic preconditioning(IPC) has been shown to decrease liver injury and to increase hepatic microvascular perfusion after liver ischemia reperfusion. This study aimed to evaluate the effects of IPC on hemodynamics of the portal venous system. METHODS: Thirty-two rats were randomized into two groups: IPC group and control group. The rats of the IPC group underwent IPC by 10 minutes of liver ischemia followed by 10 minutes of reperfusion before liver ischemia, and the rats of the control group were subjected to 60 minutes of partial liver ischemia. Non-ischemic lobes were resected immediately after reperfusion. The animals were studied at 4 hours and 12 hours after reperfusion. Mean arterial pressure, heart rate, portal vein flow and pressure were analyzed. Blood was collected for the determination of the levels of aspartate aminotransferase, alanine aminotransferase, calcium, lactate, pH, bicarbonate, and base excess. RESULTS: IPC increased the mean portal vein flow at 4 hours and 12 hours after reperfusion. IPC recovered 78% of the meanportal vein flow at 12 hours after reperfusion. IPC decreased the levels of aspartate aminotransferase, alanine aminotransferase and lactate, and increased the levels of ionized calcium, bicarbonate and base excess at 12 hours after reperfusion. CONCLUSIONS: This study demonstrated that IPC increases portal vein flow and enhances hepatoprotective effects in liver ischemia reperfusion. The better recovery of portal vein flow after IPC may be correlated with the lower levels of transaminases and with the better metabolic profile.

Remote ischemic preconditioning protects liver ischemia-reperfusion injury by regulating eNOS-NO pathway and liver microRNA expressions in fatty liver rats

BACKGROUND: Ischemic preconditioning (IPC) is a strategy to reduce ischemia-reperfusion (I/R) injury. The protective effect of remote ischemic preconditioning (RIPC) on liver I/R injury is not clear. This study aimed to investigate the roles of RIPC in liver I/R in fatty liver rats and the involvement of endothelial nitric oxide synthase-nitric oxide (eNOS-NO) pathway and microRNA expressions in this process. METHODS: A total of 32 fatty rats were randomly divided into the sham group, I/R group, RIPC group and RIPC+I/R group. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and nitric oxide (NO) were measured. Hematoxylin-eosin staining was used to observe histological changes of liver tissues, TUNEL to detect hepatocyte apoptosis, and immunohistochemistry assay to detect heat shock protein 70 (HSP70) expression. Western blotting was used to detect liver inducible NOS (iNOS) and eNOS protein levels and realtime quantitative polymerase chain reaction to detect miR-34a, miR-122 and miR-27b expressions. RESULTS: Compared with the sham and RIPC groups, serum ALT, AST and iNOS in liver tissue were significantly higher in other two groups, while serum NO and eNOS in liver tissue were lower, and varying degrees of edema, degeneration and inflammatory cell infiltration were found. Cell apoptosis number was slightly lower in the RIPC+I/R group than that in I/R group. Compared with the sham group, HSP70 expressions were significantly increased in other three groups (all P<0.05). Compared with the sham and RIPC groups, elevated miR-34a expressions were found in I/R and RIPC+I/R groups (P<0.05). MiR-122 and miR-27b were found significantly decreased in I/R and RIPC+I/R groups compared with the sham and RIPC groups (all P<0.05). CONCLUSION: RIPC can reduce fatty liver I/R injury by affecting the eNOS-NO pathway and liver microRNA expressions.

Ischemic preconditioning protects against ischemic brain injury

In this study, we hypothesized that an increase in integrin αβand its co-activator vascular endothelial growth factor play important neuroprotective roles in ischemic injury. We performed ischemic preconditioning with bilateral common carotid artery occlusion for 5 minutes in C57BL/6J mice. This was followed by ischemic injury with bilateral common carotid artery occlusion for 30 minutes. The time interval between ischemic preconditioning and lethal ischemia was 48 hours. Histopathological analysis showed that ischemic preconditioning substantially diminished damage to neurons in the hippocampus 7 days after ischemia. Evans Blue dye assay showed that ischemic preconditioning reduced damage to the blood-brain barrier 24 hours after ischemia. This demonstrates the neuroprotective effect of ischemic preconditioning. Western blot assay revealed a significant reduction in protein levels of integrin αβ, vascular endothelial growth factor and its receptor in mice given ischemic preconditioning compared with mice not given ischemic preconditioning 24 hours after ischemia. These findings suggest that the neuroprotective effect of ischemic preconditioning is associated with lower integrin αβand vascular endothelial growth factor levels in the brain following ischemia.

Ischemic Preconditioning Inhibits Over-expression of Arginyl-tRNA Synthetase Gene Rars in Ischemia-injured Neurons

The expression changes of Rars gene in ischemia-injured neurons were investigated by detecting its translational product arginyl-t RNA synthetase（Arg RS）, and the inhibitory effects of ischemic preconditioning（IPC） on Rars gene were explored. Both IPC model and prolonged ischemia（PI） model were established by using the classic oxygen glucose deprivation（OGD） method. The primary cultured neurons were assigned into the following groups： the experimental group（IPC＋PI group）, undergoing PI after a short period of IPC; the conditional control group（PI control group）, subjected to PI without IPC; blank control group, the normally cultured neurons. The Rars transcriptional activities and Arg RS expression levels were measured at different time points after re-oxygenation（3 h/6 h/12 h/24 h）. Data were collected and statistically analyzed. Compared to the blank control group, the Rars activities and Arg RS levels were significantly increased in PI control group, peaking at the time point of 6 h after re-oxygenation. Rars activities and Arg RS levels were significantly lower in the experimental group than in the PI control group at different time points after re-oxygenation. PI insult can induce an escalating activity of Rars and lead to Arg RS over-expression in primary cultured neurons. IPC can inhibit the increased Rars activity and down-regulate Arg RS expression of ischemia-insulted neurons. This mechanism may confer ischemic tolerance on neurons.

Protective effect of ischemic preconditioning on hepatic ischemia-reperfusion injury by advancing the expressive phase of survivin in rats

BACKGROUND: Survivin is a new and important gene in the regulation of apoptosis. It is very important to explore the effect of the expression of survivin protein caused by ischemia-reperfusion (IR) injury. The effect of IR injury caused by ischemic preconditioning (IP) on the liver in rats and the relation between the protective effect of IP and the expression of survivin are unclear. METHODS: One hundred and fifty male Wistar rats (weighing 190-210 g, aged 6-7 weeks) were divided into three groups at random: ischemic preconditioning (IP), ischemia-reperfusion (IR) and sham-operation (SO). Sample specimens were collected from each group at 6, 12, 24, 48, and 72 hours after reperfusion. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured by an automatic biochemical analyzer. Malondialdehyde (MDA) in liver tissue was measured. Pathological changes in the liver and immunohistochemical staining for survivin were determined with an optical microscope. RESULTS: The ALT levels in the IP and IR groups after reperfusion at each time were higher than those in the SO group (P<0.05), whereas after reperfusion for 6 and 12 hours, the ALT levels in the IP group were lower than those in the IR group (P<0.05). The AST levels in all IP and IR groups were higher than those in the SO group (P<0.05), whereas after reperfusion for 12, 24, 48 and 72 hours, the AST levels in the IP group were lower than those in the IR group (P<0.05). The MDA concentrations after reperfusion in the IP group were lower than those in the IR group (P<0.05), though the MDA concentrations in the IP and IR groups increased in contrast to those in the SO group after reperfusion at each time (P<0.05). After reperfusion for 12, 24, 48 and 72 hours, the number of survivin-positive cells was larger in the IP and IR groups than in the SO group (P<0.05). After reperfusion for 12, 24, and 48 hours the number of survivin-positive cells in the IP group increased compared with that in the IR group (P<0.05). CONCLUSIONS: IR increases the protein expression of survivin in liver tissue. IP inhibits the accumulation of MDA, advances the expressive phase of survivin protein in hepatic tissue, and improves liver function.

Protection of retinal ganglion cells against optic nerve injury by induction of ischemic preconditioning

AIM： To explore if ischemic preconditioning （IPC） can enhance the survival of retinal ganglion cells （RGCs） after optic nerve axotomy. METHODS： Twenty-four hours prior to retinal ischemia 60min or axotomy, IPC was applied for ten minutes in groups of （n=72） animals. The survival of RGCs, the cellular expression of heat shock protein 27 （HSP27） and heat shock protein 70 （HSP70） and the numbers of retinal microglia in the different groups were quantified at 7 and 14d post-injury. The cellular expression of HSP27 and HSP70 and changes in the numbers of retinal microglia were quantified to detect the possible mechanism of the protection of the IPC. RESULTS： Ten minutes of IPC promoted RGC survival in both the optic nerve injury （IPC-ONT） and the retinal ischemia 60min （IPC-IR60） groups, examined at 7d and 14d post-injury. Microglial proliferation showed little correlation with the extent of benefit effects of IPC on the rescue of RGCs. The number of HSP27-positive RGCs was significantly higher in the IPC-ONT group than in the sham IPC-ONT group, although the percentage of HSP27-positive RGCs did not significantly differ between groups. For the IPC-IR60 group, neither the number nor the percentage ofthe HSP27-positive RGCs differed significantly between the IPC and the sham-operated groups. The number of HSP70-positive RGCs was significantly higher for both the IPC-ONT and the IPC-IR60 experimental groups, but the percentages did not differ. CONCLUSION： The induction of IPC enhances the survival of RGCs against both axotomy and retinal ischemia.

Effect of remote ischemic preconditioning among donors and recipients following pediatric liver transplantation:A randomized clinical trial

BACKGROUND Studies suggested that remote ischemic preconditioning(RIPC)may effectively lessen the harmful effects of ischemia reperfusion injury during organ transplantation surgery.AIM To investigate the protective effects of RIPC on living liver donors and recipients following pediatric liver transplantation.METHODS From January 2016 to January 2019 at Renji Hospital Affiliated with Shanghai Jiao Tong University School of Medicine,208 donors were recruited and randomly assigned to four groups:S-RIPC group(no intervention;n=55),D-RIPC group(donors received RIPC;n=51),R-RIPC group(recipients received RIPC,n=51)and DR-RIPC group(both donors and recipients received RIPC;n=51).We primarily evaluated postoperative liver function among donors and recipients and incidences of early allograft dysfunction,primary nonfunction and postoperative complications among recipients.RESULTS RIPC did not significantly improve alanine transaminase and aspartate aminotransferase levels among donors and recipients or decrease the incidences of early allograft dysfunction,primary nonfunction,and postoperative complications among recipients.Limited protective effects were observed,including a lower creatinine level in the D-RIPC group than in the S-RIPC group on postoperative day 0(P<0.05).However,no significant improvements were found in donors who received RIPC.Furthermore,RIPC had no effects on the overall survival of recipients.CONCLUSION The protective effects of RIPC were limited for recipients who received living liver transplantation,and no significant improvement of the prognosis was observed in recipients.

Ischemic preconditioning enhances hepatocyte proliferation in the early phase after ischemia under hemi-hepatectomy in rats

BACKGROUND: Ischemia/reperfusion (I/R) injury is an important barrier to liver surgery and transplantation because it impairs remnant liver/reduced-size-graft regeneration. Ischemic preconditioning (IPC), as an effective measure to overcome I/R injury, has been shown to enhance the regenerative capacity of hepatocytes. However, investigations have always focused on regeneration in the late phase after reperfusion. This study aimed to investigate whether IPC enhances hepatocyte proliferation in the early phase after reperfusion and possible underlying mechanisms. METHODS: A total of 90 rats were divided into three groups: hemi-hepatectomy alone (PHx group), 60 minutes of ischemia plus hemi-hepatectomy (I/R group), and a cycle of 10 minutes of alternating I/R prior to 60 minutes of ischemia plus hemi-hepatectomy (IPC group). Each group was divided into five subgroups sacrificed after 0.5, 2, 6, 12 or 24 hours (n=6/ subgroup). Subsequently, serum concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) were measured; caspase-3 and proliferating cell nuclear antigen (PCNA) proteins were also determined by Western blotting. Furthermore, PCNA was detected by immunohistochemistry to identify the expression site.RESULTS: Serum ALT and AST levels after 2-24 hours of reperfusion in the PHx and IPC groups were remarkably decreased compared to the I/R group, and the serum TNF-α was relatively lower. A significant increase of serum IL-6 levels was found in the PHx and IPC groups compared with the I/R group at each time point. Furthermore, PCNA expression was remarkably increased in the IPC group after 6-12 hours of reperfusion, and in the earlier 0.5 and 6 hours time points after reperfusion have shown the massive PCNA-positive hepatocytes. At the same time, the expression of liver p-JNK was higher in the IPC group in the early phase after reperfusion than that of the I/R group and its expression was consistent with the PCNA. CONCLUSION: IPC can initiate hepatocyte proliferation in the early phase after ischemia under hemi-hepatectomy, and may be associated with p-JNK expression and triggered by TNF-α/IL-6 signals.