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.
ObjectiveTo understand the current research progress on the role of hydrogen sulfide (H2S) in liver diseases. MethodThe relevant literature on the role of H2S in the liver diseases published in recent years was retrieved and reviewed. ResultsCurrent research focused primarily on exploring the mechanisms of H2S in various liver diseases. Studies had shown that H₂S played an important role in the occurrence and development of liver diseases through mechanisms such as antioxidative stress, anti-inflammatory effects, regulation of autophagy, endoplasmic reticulum stress, angiogenesis, and cell death. ConclusionsBy supplementing exogenous H2S, adjusting the gut microbiota, or inhibiting key enzymes involved in H₂S synthesis, the concentration of H2S in the body can be modulated, providing new strategies for treating liver diseases. However, the related mechanisms are still controversial. Future research should further investigate the specific role of H2S in different liver diseases and how to precisely control its level in the body to achieve targeted drug delivery.
Acute lung injury is a kind of common complication after cardiopulmonary bypass. Acute lung injury is attributed to the ischemia-reperfusion injury and systemic inflammatory response syndrome. Several factors common in cardiac surgery with cardiopulmonary bypass may worsen the risk for acute lung injury including atelectasis, transfusion requirement, older age, heart failure, emergency surgery and prolonged duration of bypass. Targets for prevention of acute lung injury include mechanical, surgical and anesthetic interventions that aim to reduce the contact activation, systemic inflammatory response, leukocyte sequestration and hemodilution associated with cardiopulmonary bypass. We aim to review the etiology, risk factors and lung protective strategies for acute lung injury after cardiopulmonary bypass.
ObjectiveTo observe the protective effect of tanshinone Ⅱ A on the mouse liver ischemia-reperfusion injury (IRI) model and preliminarily explore its mechanism of alleviating liver injury.MethodsThe IRI mouse model was established after the pre-treating with tanshinone Ⅱ A. Then, the serum and liver tissue of mice were collected to detect the changes of liver function, histopathology, liver cell apoptosis, and inflammatory factors. In addition, the protein expression levels of high mobility group box 1 (HMGB1), advanced glycosylation end-product specific receptor (RAGE), and Toll like receptor 4 (TLR4) in the liver tissues were detected by the Western blot method.ResultsAll data were analyzed by the homogeneity of variance test. The results of factorial design showed that the levels of ALT and AST in the serum, the pathological score and apoptosis index, the inflammatory response, as well as the expressions of HMGB1, TLR4 and RAGE proteins in the liver tissues were decreased significantly (P<0.05) in the sham operatation plus tanshinone Ⅱ A mice, which were increased significantly (P<0.05) in the IRI mice, which were antagonized synergistically by the tanshinone ⅡA and IRI (P<0.05).ConclusionsTanshinone ⅡA could reduce the liver IRI and inflammatory response in mouse. These effects might be related to the down-regulations of TLR4, HMGB1, and RAGE expressions.
ObjectiveTo compare the myocardial protective effect of HTK solution and St.ThomasⅡ(STH) solution in immature rabbit myocardium at different cardiac arrest time. MethodsAccording to cardioplegia and cardiac arrest time, 32 immature New Zealand white rabbits (aged 2-3 weeks) were randomly divided into four groups. A group SO (8 rabbits) underwent 1 hour cardiac arrest with STH solution, a group ST (8 rabbits) underwent 2 hours cardiac arrest with STH solution, a group HO (8 rabbits) underwent 1 hour cardiac arrest with HTK solution, a group Ht (8 rabbits) underwent 2 hours cardiac arrest with HTK solution. Compare the myocardial protective effect of HTK and STH solution in immature myocardium at different cardiac arrest time. ResultsThe Langendorff models were successfully established in 30 cases (8 cases in the group SO and HO, 7 cases in the group ST and HT). There were no statistical differences in hemodynamics and myocardial enzyme (CK-MB, LDH) (P > 0.05), but HTK solution reduced the activity of nitric oxide synthase (NOS) and content of malonaldehyde (MDA) and NO, maintained high activity of superoxide dismutase (SOD) and Ca2+-ATPase (P < 0.05), performed more effective myocardial protection for immature myocardium. ConclusionHTK solution has more effective myocardial protection for immature myocardium than STH solution does, but STH solution still has good outcomes within short cardiac arrest time (1h).
Objective To investigate the effect of N-acetylserotonin (NAS) on the retinal microglia polarization in retinal ischemia-reperfusion injury (RIRI) rats and explore its mechanism via nucleotide-bound oligomeric domain 1 (NOD1)/receptor interacting protein 2 (Rip2) pathway. MethodsHealthy male Sprague Dawley rats were randomly divided into Sham (n=21), RIRI (n=21) and NAS (injected intraperitoneally 30 min before and after modeling with NAS, 10 mg/kg, n=18) groups, using random number table. And the right eye was used experimental eye. The RIRI model of rats in RIRI group and NAS group was established by anterior chamber high intraocular pressure method. Rats in NAS group were intraperitoneally injected with 10 mg/kg NAS before and 30 min after modeling, respectively. The retinal morphology and the number of retinal ganglion cell (RGC) in each group were detected by hematoxylin-eosin staining and immunohistochemical staining. The effect of NAS on polarization of retinal microglia was detected by immunofluorescence staining. Transcriptome sequencing technology was used to screen out the differentially expressed genes between Sham and RIRI groups. Western blot and real-time quantitative polymerase chain reaction (RT-PCR) were used to examine the differentially expressed genes. Immunohistochemical staining, Western blot and RT-PCR were used to investigate the effect of NAS on the expression of NOD1 and Rip2 protein and mRNA in retinal tissue and microglia of rats. General linear regression analysis was performed to determine the correlation between the number difference of NOD1+ cells and the number difference of M1 and M2 microglia in retinal tissues of rats in NAS group and RIRI group. ResultsA large number of RGC were observed in the retina of rats in Sham group. 24 h after modeling, compared with Sham group, the inner retinal thickness of rats in RIRI group was significantly increased and the number of RGC was significantly decreased. The thickness of inner retina in NAS group was significantly thinner and the number of RGC was significantly increased. Compared with Sham group, the number of retinal microglia of M1 and M2 in RIRI group was significantly increased. Compared with RIRI group, the number of M1 microglia decreased significantly and the number of M2 microglia increased significantly in NAS group. There was statistical significance in the number of M1 and M2 microglia in the retina of the three groups (P＜0.05). Transcriptome sequencing results showed that retinal NOD1 and Rip2 were important differential genes 24 h after modeling. The mRNA and protein relative expressions of NOD1 and Rip2 in retina of RIRI group were significantly higher than those of Sham group, with statistical significance (P＜0.05). The number of NOD1+ and Rip2+ cells and the relative expression of mRNA and protein in retinal microglia in RIRI group were significantly higher than those in Sham group, and NAS group was also significantly higher than that in Sham group, but lower than that in RIRI group, with statistical significance (P＜0.05). The number of Iba-1+/NOD1+ and Iba-1+/Rip2+ cells in retinal microglia in RIRI group was significantly increased compared with that in Sham group, and the number of Iba-1+/Rip2+ cells in NAS group was significantly decreased compared with that in RIRI group, but still significantly higher than that in Sham group, with statistical significance (P＜0.05). Correlation analysis results showed that the difference of retinal NOD1+ and Rip2+ cells in NAS group and RIRI group was positively correlated with that of M1 microglia (r=0.851, 0.895), and negatively correlated with that of M2 microglia (r=−0.797, −0.819). The differences were statistically significant (P＜0.05). ConclusionNAS can regulate the microglial polarization from M1 to M2 phenotype, the mechanism is correlated with the NOD1/Rip2 pathway.
Objective To investigate the optimal dosage of bone marrow mesenchymal stem cells （BMSCs） transplantations for treatment of hepatic ischemia-reperfusion injury in rats， and to provide prophase experimental basis for it. Methods BMSCs of Wistar rats were isolated and cultivated by bone marrow adherent culture method. BMSCs of the fourth generation were prepared for cell transplantation. Thrity hepatic ischemia-reperfusion injury models of maleWistar rats were successfully established， and then were randomly divided into blank control group， 5×105 group， 1×106group， 2×106 group， and 3×106 group， each group enrolled 6 rats. The 200 μL cell suspension of BMSCs were transfusedinto the portal vein with number of 5×105， 1×106， 2×106， and 3×106 separately in rats of later 4 groups， and rats of blank control group were injected with phosphate buffered saline of equal volume. At 24 hours after cell transplantation， blood samples were collected to test aspartate aminotransferase （AST） and alanine aminotransferase （ALT）， liver tissueswere obtained to test malonaldehyde （MDA）， superoxide dismutase （SOD）， and nuclear factor-κB （NF-κB） p65 protein.Liver tissues were also used to perform HE staining to observe the pathological changes. Results Compared with blank control group， 5×105 group， and 3×106 group， the levels of AST， ALT， and MDA were lower （P＜0.05） while activity levels of SOD were higher （P＜0.05） in 1×106 group and 2×106 group， and expression levels of NF-κB p65 protein were lower with the pathological injury of liver tissue improved， but there were no significant differences on levels of AST， ALT， MDA， and SOD （P＞0.05）， and both of the 2 groups had the similar pathological change. Conclusion The optimal dosage of the BMSCs transplantations after hepatic ischemia-reperfusion injury is 1×106.
Objective To investigate the targeted combination and anti-inflammatory effects of anti-intercellular adhesion molecule 1 (ICAM-1) targeted perfluorooctylbromide (PFOB) particles on myocardial ischemia-reperfusion injury in rat model. Methods Seventy-six adult Sprague Dawley rats (male or female, weighing 250-300 g) were selected for experiment. The models of myocardial ischemia-reperfusion injury were established by ligating the left anterior descending coronary artery for 30 minutes in 30 rats. The expression of ICAM-1 protein was detected by immunohistochemistry staining at 6 hours after reperfusion, and the normal myocardium of 10 rats were harvested as control; then the content of interleukin 8 (IL-8) in serum was tested every 6 hours from 6 hours to 48 hours after reperfusion. The other 36 rats were randomly divided into 6 groups (n=6): ischemia-reperfusion injury model/targeted PFOB particles group (group A), ischemia-reperfusion injury model/untargeted PFOB group (group B), normal control/targeted PFOB particles group (group C), normal control/untargeted PFOB particles group (group D), ischemia-reperfusion injury model/normal saline group (group E), and sham operation group (group F). The ischemia-reperfusion injury models were established in groups A, B, and E; while a thread crossed under the coronary artery, which was not ligated after open-chest in group F. After 6 hours of reperfusion, 1 mL of corresponding PFOB particles was injected through juglar vein in groups A, B, C, and D, while 1 mL of nomal saline was injected in group E. Ultrasonography was performed in groups A, B, C, and D before and after injection. The targeted combination was tested by fluorescence microscope. The content of IL-8 was tested after 6 and 24 hours of reperfusion by liquid chip technology in groups A, B, E, and F. Results After 6 hours of reperfusion, the expression of ICAM-1 protein significantly increased in the anterior septum and left ventricular anterior wall of the rat model. The content of IL-8 rised markedly from 6 hours after reperfusion, and reached the peak at 24 hours. Ultrasonography observation showed no specific acoustic enhancement after injection of PFOB particles in groups A, B, C, and D. Targeted combination was observed in the anterior septum and left ventricular anterior wall in group A, but no targeted combination in groups B, C, and D. There was no significant difference in the content of IL-8 among groups A, B, and E after 6 hours of reperfusion (P gt; 0.05), but the content in groups A, B, and E was significantly higher than that in group F (P lt; 0.05). After 24 hours of reperfusion, no sigificant difference was found in the content of IL-8 between groups A and B (P gt; 0.05), but the content of IL-8 in groups A and B were significantly lower than that in group E (P lt; 0.05). Conclusion Anti-ICAM-1 targeted PFOB particles can target to bind and pretect injured myocardium of rat by its anti-inflammation effects.
ObjectiveTo observe the effects of overexpression of S100A4 protein on retinal capillary cells and retinal ganglion cells (RGC) after retinal ischemia-reperfusion injury (RIRI). MethodsOne hundred healthy adult male C57BL/6 mice were randomly divided into normal control group (group C), RIRI group, adeno-associated virus (AAV2)-S100A4 green fluorescent protein (GFP) intravitreal injection group (group S), RIRI+AAV2-GFP intravitreal injection group (group GIR), and RIRI+AAV2-S100A4-GFP intravitreal injection group (group SIR), with 20 mice in each group. The RIRI model was established using the high intraocular pressure anterior chamber method in the RIRI, GIR and SIR groups of mice. Eyes were enucleated 3 days after modelling by over anaesthesia. The number of retinal capillary endothelial cells and pericytes in the retinal capillaries of mice in each group was observed by retinal trypsinised sections and hematoxylin-eosin and periodic acid-Schiff staining; immunofluorescence staining was used to observe endothelial cell, pericyte coverage and RGC survival; The relative expression of Toll-like receptor 4 (TLR4), p38 MAPK and nuclear factor erythroid 2-related factor 2 (NRF2) in retinal tissues was measured by Western blot. One-way analysis of variance was used to compare data between groups. ResultsThree days after modeling, the endothelial cell to pericyte ratio in group C was compared with group S and SIR, and the difference was not statistically significant (F=106.30, P＞0.05); the SIR group was compared with group RIRI and GIR, and the difference was statistically significant (F=106.30, P＜0.000 1). Comparison of endothelial cell coverage in each group, the difference was not statistically significant (F=3.44, P＞0.05); compared with the pericyte coverage in group C, the RIRI group and the GIR group were significantly lower, and the difference was statistically significant (F=62.69, P＜0.001). Compared with the RGC survival rate in group C, it was significantly lower in RIRI and GIR groups, and the difference was statistically significant (F=171.60, P＜0.000 1); compared with RIRI and GIR groups, the RGC survival rate in SIR group was significantly higher, and the difference was statistically significant (F=171.60, P＜0.000 1). The relative expression levels of TLR4, p38 and NRF2 proteins were statistically significant among all groups (F=42.65, 20.78, 11.55; P＜0.05). ConclusionsPericytes are more sensitive to ischemia than endothelial cells after retinal RIRI in mice, and early vascular cell loss is dominated by pericytes rather than endothelial cells. The overexpression of S100A4 protein protects against loss of pericytes and RGC after RIRI by inhibiting the TLR4/p38/NRF2 signaling pathway.
ObjectiveTo explore performances of functional magnetic resonance imaging (MRI) in evaluation of hepatic warm ischemia-reperfusion injury.MethodThe relative references about the principle of functional MRI and its application in the assessment of hepatic warm ischemia-reperfusion injury were reviewed and summarized.ResultsThe main functional MRI techniques for the assessment of hepatic warm ischemia-reperfusion injury included the diffusion weighted imaging (DWI), intravoxel incoherent motion (IVIM), diffusion tensor imaging (DTI), blood oxygen level dependent (BOLD), dynamic contrast enhancement MRI (DCE-MRI), and T2 mapping, etc.. These techniques mainly used in the animal model with hepatic warm ischemia-reperfusion injury currently.ConclusionsFrom current results of researches of animal models, functional MRI is a non-invasive tool to accurately and quantitatively evaluate microscopic information changes of liver tissue in vivo. It can provide a useful information on further understanding of mechanism and prognosis of hepatic warm ischemia-reperfusion injury. With development of donation after cardiac death, functional MRI will play a more important role in evaluation of hepatic warm ischemia-reperfusion injury.