ObjectiveTo summarize the research advances of pyroptosis in hepatic ischamia-reperfusion injury (IRI).MethodThe literatures about the studies of mechanism of pyroptosis in hepatic IRI were retrieved and analyzed.ResultsPyroptosis, also known as inflammatory necrocytosis, was proven to play an important role in the hepatic IRI. When hepatic ischemia-reperfusion occurred, the classical pathway of pyroptosis dependenting on caspase-1 and the non-classical pathway of pyroptosis dependenting on caspase-11 were initiated by specific stimulants, and leaded to the activation of gasdermin D, releases of proinflammatory factors such as interleukin-1β, interleukin-18, etc., and the recruitment and activation of neutrophils. Consequently, pyroptosis caused more severe hepatic inflammation and aggravated existing cell injury and dysfunction of liver during hepatic IRI.ConclusionsPyroptosis plays an important role in liver IRI. Further researches about mechanism of pyroptosis will be beneficial to the prevention and treatment of the pyroptosis of related diseases.
【Abstract】ObjectiveOn the basis of traditional transplantation model, a successful model of pancreaticoduodenal transplantation (PDT) were established in rats, which is the foundation of basic and clinical transplantation research. Methods We improved the technique of microoperation on donor and harvested high-quality graft. The dual cuff technique was applied to end-to-end anastomose proximal part of abdominal aorta and portal vein with left renal aorta and vein of recipient, and distal part of abdominal aorta was connected with Y-tube. External secretion was performed by duodenum stoma. The PDT model was finished without blocking systemic circulation and portal vein system. Random blood glucose levels and drainage were monitored postoperatively to evaluate the function of endocrine and ectocrine. Results Thirty operations were done. The total procedure of transplantation lasted 2 hours. Moreover the operation on recipient and the reconstruction of vessels took only (26±5) and (25±5) minutes, respectively. The success rate was elevated to 100%. The ectocrine function was restored within 2 hours after operation. Except for 3 cases of non-function graft because of thrombosis in cannula, the glucose level of the remaining recipients was reduced to normal level 6 h or 24 h after transplantation. The survival rate of graft function was 90% (27/30). Conclusion This model is finished without special equipment and can recover the endocrine function in advance. It is a simple and stable model, which might be used in research of the theoretical problems involved in clinical pancreas transplantation.
Objective To investigate the maximum tolerance limit of rats to hepatic inflow occlusion with portal vein blood bypss (PBB) in normothermia. Methods First. A new animal model was established, the animal survival rate were calculated following 7 days of reperfusion after hepatic inflow occlusion of 30, 60, 90, 100, 110, 120 min or portal triad clamping (PTC) of 30 min. And then, the hepatic energy metabolism (RCR, P/O, ATP, AKBR) was studied following 30, 90, 120 min of ischemia or 1, 6, and 24 hours of reperfusion after the ischemia. According to the reversibility of the hepatic motochondrial function injury and maximum as long as a period of liver warm ischemia of all animal postoperative 7 days survial, the safe limit of rat to hepatic inflow occlusion was evaluated. Results The survival rate on postoperative 7 days was one hundred percent subjected to 30, 60 and 90 min of hepatic inflow occlusion, and 50, 30, 20 percent in 100, 110, 120 min, respectively, the survival rate in rats with 30 min of portal triad champing was about 40 percent. The parameters of hepatic motochondrial function reflecting the degree of liver damage to ischemia showed significantly different as compared to sham group. The functional lesion was exacerbated during inital reperfusion, then was restored progressively in PBB-30 min and PBB-90 min groups, but was maintained low level in PBB-120 min and PTC-30 min groups.Conclusion The 90 minutes is the maximum limit of rats to hepatic inflow occlusion in normothermia.
Objective To investigate the research base and current understanding of the mechanism of ischemia-reperfusion injury (IR) to intrahepatic cholangiocytes after l iver transplantation, so as to identify the key points of the mechanism and provide references for cl inical practice. Methods We searched PubMed (1970 to 2007) and CBM(1979 to 2007). Qual ity assessment and data collection were performed by two reviewers independently. Since the baseline supplied and the measure were very different, we decided to provide a descriptive summary only. Results The earliest study on liver IR was publ ished in 1970. A total of 65 papers were included. There were 13 on cl inical studies, 35 on basic research studies; and 17 review articles. Most basic studies focus on injury mechanism: ① The physiology of bile ducts and Intrahepatic Bil iary Duct Cells(IBDC); ②the IR caused injury mechanism of IBDC during or after liver transplantation; ③ the basic injury mechanisms include: cold ischemia, warm ischemia, reperfusion, injury of bile and bile salts. Most clinical studies focused on preventive measures, including surgical and non-surgical approaches. Based on the evidence from basic research, changing the composition and perfusion methods of perfusate and protecting the specific blood supply to biliary ducts and cholangiocytes during the operation were important in preventing or reducing such an injury. Conclusion ① The heterogeneity of morphology, function, status and the special blood supply in large and small IBDC are important material base. ② Our own study indicated that simple IR or H/R was able to change the expression of MHC, MIC, DR4, DR5 and other adhesion molecules. ③ Compared to hepatic cells, hIBDC can’ t resist cold ischemia and even worse in tolerating reperfusion injury. ④ Hydrophobic bile salts will could increase the harm to bile ducts during organ preservation. ⑤ Due to the low quantity and limited quantities of clinical researches, the power of evidence was low. The evaluation indexes and baseline conditions are not unified. So the conclusions are for reference only.
Objective To identify the N6-methyladenosine (m6A)-related characteristic genes analyzed by gene clustering and immune cell infiltration in myocardial ischemia-reperfusion injury (MI/RI) after cardiopulmonary bypass through machine learning. Methods The differential genes associated with m6A methylation were screened by the dataset GSE132176 in GEO, the samples of the dataset were clustered based on the differential gene expression profile, and the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the differential genes of the m6A cluster after clustering were performed to determine the gene function of the m6A cluster. R software was used to determine the better models in machine learning of support vector machine (SVM) model and random forest (RF) model, which were used to screen m6A-related characteristic genes in MI/RI, and construct characteristic gene nomogram to predict the incidence of disease. R software was used to analyze the correlation between characteristic genes and immune cells, and the online website was used to build a characteristic gene regulatory network. Results In this dataset, a total of 5 m6A-related differential genes were screened, and the gene expression profiles were divided into two clusters for cluster analysis. The enrichment analysis of m6A clusters showed that these genes were mainly involved in regulating monocytes differentiation, response to lipopolysaccharides, response to bacteria-derived molecules, cellular response to decreased oxygen levels, DNA transcription factor binding, DNA-binding transcription activator activity, RNA polymerase Ⅱ specificity, NOD-like receptor signaling pathway, fluid shear stress and atherosclerosis, tumor necrosis factor signaling pathway, interleukin-17 signaling pathway. The RF model was determined by R software as the better model, which determined that METTL3, YTHDF1, RBM15B and METTL14 were characteristic genes of MI/RI, and mast cells, type 1 helper lymphocytes (Th1), type 17 helper lymphocytes (Th17), and macrophages were found to be associated with MI/RI after cardiopulmonary bypass in immune cell infiltration. Conclusion The four characteristic genes METTL3, YTHDF1, RBM15B and METTL14 are obtained by machine learning, while cluster analysis and immune cell infiltration analysis can better reveal the pathophysiological process of MI/RI.
Objective To observe the influences of depolarized arrest and hyperpolarized arrest on alternation of fluidity of myocardial cell membrane during cardiopulmonary bypass (CPB) and evaluate the protective effects on myocardium of hyperpolarized arrest. Methods Seventy-two felines were randomized into three groups, each group 24. Control group: 180 minutes of CPB was conducted without aortic and vena caval cross-clamping. Depolarized arrest group: hearts underwent 60 minutes of global ischemia after aortic cross-clamping (ACC) followed by 90 minutes of reperfusion. The cardioplegic solution consisted of St. Thomas solution (K+16mmol/L). Hyperpolarized arrest group: the protocol was the same as that in depolarized arrest group except that the cardioplegic solution consisted of St.Thomas solution with pinacidil (50 mmol/L,K+5mmol/L). Microviscosity, the reciprocal of fluidity of myocardial membrane was measured in all groups by using fluorescence polarization technique. (Results )Microvis cosity of myocardial cell in depolarized arrest group during ACC period was significantly higher than that before ACC and kept on rising during reperfusion period. Microviscosity of myocardial cell in hyperpolarized arrest group during ACC was trending up and reperfusion periods as well, but markedly lower compared to that in depolarized arrest group at corresponding time points(Plt;0.01). Conclusion Hyperpolarized arrest is more effective in protecting myocardial cells from ischemia-reperfusion injury than depolarized arrest during CPB by maintaining better fluidity of myocardial membrane.
ObjectiveTo investigate relationship between liver non-parenchymal cells and hepatic ischemia-reperfusion injury (HIRI).MethodThe relevant literatures on researches of the relationship between HIRI and liver non-parenchymal cells were analyzed and reviewed.ResultsDuring HIRI, hepatocytes could be severely damaged by aseptic inflammatory reaction and apoptosis. The liver non-parenchymal cells included Kupffer cells, sinusoidal endothelial cells, hepatic stellate cells, and dendritic cells, which could release a variety of cytokines and inflammatory mediators to promote the damage, and some liver non-parenchymal cells also had effect on reducing HIRI, for example: Kupffer cells could express heme oxygenase-1 to reduce HIRI, and hepatic stellate cells may participate in the repair process after HIRI. The role of liver non-parenchymal cells in HIRI was complex, but it also had potential therapeutic value.ConclusionLiver non-parenchymal cells can affect HIRI through a variety of mechanisms, which provide new goals and strategies for clinical reduction of HIRI.
OBJECTIVE: To investigate the injury on isolated testes induced by ischemia/reperfusion(I/R), and the protective effect of Yisheng injection on the injury. METHODS: Twenty-six isolated cadaver testes contributed by 13 persons were preserved with 4 degrees C 250 ml hypertonic citrate alloxuric (HCA) solution and then reperfused with 37 degrees C 500 ml HCA. Solution of experimental group contained 500 micrograms/ml Yisheng injection. In simple cold preservation test, involving in 8 experimental and 8 control testes, a series of time points (6, 12, 18, 24, 36, 48, 60, 72 hours) were set to harvest. 10 testes (1 testis respectively on 6, 12, 18, 24 and 36 hours in experimental and control groups) were reperfused with 37 degrees C HCA for 6 and 12 hours. Histological and histochemical changes were observed. RESULTS: In the experimental testes, 4 degrees C cold preservation in 24 hours could not induce obvious pathologic changes. After 24 hours, changes such as swelling, vacuolar degeneration or detachment of endothelial cells (ECs), separation between basement membrane and seminiferous epithelium, mal-alignment of spermatogenous cell and edema of mesenchyme could be observed. In the testes preserved for 12 hours, the activity of lactic dehydrogenase(LDH) and succinic dehydrogenase (SDH) increased, then fallen after 24 hours. The activity of Nitric oxide synthetase(NOS) decreased after 18 hours. All changes were more obvious after following 37 degrees C reperfusion. In the control testes, swelling and vacuolar degeneration of ECs occurred on 12 hours cold preservation, and injury was worse along with the prolongation of cold preservation time. Pathologic changes of ECs, seminiferous epithelium and mesenchyme were serious after 37 degrees C reperfusion. CONCLUSION: 4 degrees C cold preservation in 24 hours can only cause mild ECs’ injury, and obvious abnormal testes’ histological profile can be observed beyond 24 hours. 37 degrees C reperfusion will make injury worse. Yisheng injection can keep isolated testes histologic structure well in 24 hours cold preservation, and it has protective effect on I/R injury.
Objective To study the effect of dexamethasone to protect flaps from an ischemia-reperfusion injury and elucidate its mechanism of regulating the death course of the neutrophils.Methods The rats were randomly divided into 3 groups.The vein of the rat was clamped for 8 h after the flap had formed. Group A: the normal flap; Group B: the saline control flap; Group C: the treatment flap with dexamethasone. The survival area of the flaps was measured at 7 days; the apoptotic and necrotic neutrophils,tumor necrosis factor α （TNF-α）, and interleukin 10 （IL-10） concentrations were measured. Results The flap survival areas in Groups A and C were larger than those in Group B. The apoptotic neutrophils in Group B were fewer than those in Groups A and C on the 1st and 3rd days after operation; however, they were more in number in Group B than in groups A andC on the 6th day. The necrotic cells in Group B were more in number than those in Groups A and C. In Group B, the plasma TNF-α concentration reached the maximum level at 1 h,while the IL-10 level reached the lowest 3 h after the reperfusion. In Group C, the TNF-α concentration was lower than that in Group B and decreased dramatically at 6 h. The IL-10 concentration was the lowest at 1 h, and increased rapidly at 3 h. Thus, ischemia reperfusion could injure the flaps, probably through the abnormal action of the neutrophils, such as the disordered secretion of the cytokines and abnormal death course of the neutrophils. Conclusion Dexamethasone can protect the flap from an ischemia-reperfusion injury by its regulation for the neutrophil function.
ObjectiveTo investigate the protective mechanism of prostaglandin E1 against hepatic ischemia reperfusion injury.MethodsUsing 45minute ischemiareperfusion rat model in normal temperature, PGE1 was injected into portal vein before ischemia. An hour later blood was taken from portal vein to examine the enzyme levels, including GOT, GPT, LDH and TNFα, ET1. The alteration of pathological morphology of the ischemia lobe was observed.ResultsThe three enzemes, TNFα, ET1 levels of ischemiareperfusion group were significantly higher than those of the control group (P＜0.01). The indices of the PGE1 group were much lower than those of the ischemiareperfusion group (P＜0.01), but little higher than those of the control group (P＞0.05). The control group had obvious alteration in pathological morphology, but only slight alteration in PGE1 group, compared with the control group. ConclusionPGE1 protects against ischemiareperfusion injury of the liver.
