ObjectiveTo analyze the protective mechanism of spinal cord ischemia-reperfusion injury mediated by N-methyl-D-aspartate (NMDA) receptor.MethodsA total of 42 SD rats were randomly assigned to 4 groups: a non-blocking group (n=6), a saline group (n=12), a NMDA receptor blocker K-1024 (25 mg/kg) group (n=12) and a voltage-gated Ca2+ channel blocker nimodipine (0.5 mg/kg) group (n=12). The medications were injected intraperitoneally 30 min before ischemia. The neural function was evaluated. The neuronal histologic change of spinal cord lumbar region, the release of neurotransmitter amino acids and expression of spinal cord neuronal nitric oxide synthase (nNOS) were compared.ResultsAt 8 h after reperfusion, the behavioral score of the K-1024 group was 2.00±0.00 points, which was statistically different from those of the saline group (5.83±0.41 points) and the nimodipine group (5.00±1.00 points, P<0.05). Compared with the saline group and nimodipine group, K-1024 group had more normal motor neurons (P<0.05). There was no significant difference in glutamic acid concentration in each group at 10 min after ischemia (P=0.731). The nNOS protein expression in the K-1024 group was significantly down-regulated compared with the saline group (P<0.01). After 8 h of reperfusion, the expression of nNOS protein in the K-1024 group was significantly up-regulated compared with the saline group (P<0.05).ConclusionK-1024 plays a protective role in spinal cord ischemia by inhibiting NMDA receptor and down-regulating nNOS protein expression; during the reperfusion, K-1024 has a satisfactory protective effect on spinal cord function, structure and biological activity of nerve cells.
ObjectiveTo summarize the mechanism of neutrophil extracellular traps (NETs) in hepatic ischemia-reperfusion injury (HIRI) and the research progress in targeting NETs to reduce HIRI, providing valuable reference for reducing HIRI. MethodThe related literatures at home and abroad about the role of NETs in the pathogenesis of HIRI and target NETs to alleviate HIRI were retrieved and reviewed. ResultsHIRI usually appeared in the process of liver surgery and was a common clinical problem, which occured in situations such as liver surgery, organ transplantation, liver ischemia and so on. This kind of injury would lead to tissue necrosis, inflammatory response and oxidative stress, which was a major cause of hepatic dysfunction and multiple organ failure after hepatic surgery, greatly increases the complications and mortality after hepatic surgery. NETs played a crucial role in the aseptic inflammatory response induced by hepatic ischemia/reperfusion. During hepatic ischemia-reperfusion, neutrophils promoted inflammatory cascade reactions and cytokine storms by forming NETs, exacerbating damage caused by hepatic ischemia-reperfusion. At present, some experimental and clinical studies had shown that inhibiting the formation of NETs or eliminating the formed NETs could alleviate the hepatic ischemia-reperfusion injury and improve the prognosis. ConclusionsTargeting NETs may become a new method for treating hepatic ischemia-reperfusion injury. In the future, it is foreseeable that more experiments and clinical trials will be conducted on targeted NETs for the treatment of hepatic ischemia-reperfusion injury. And gradually establish more comprehensive and effective treatment strategies, thereby providing new ways to improve the prognosis of hepatic surgery patients in clinical practice.
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.
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.
【 Abstract 】 Objective To investigate the protective effect of peroxisome proliferator-activated receptor γ (PPAR γ ) activator 15-deoxyprostaglandin J2 (15d-PGJ2) in rat hepatic ischemia-reperfusion injury and its mechanism. Methods The models of 70% warm ischemia-reperfusion injury were established in SD rats, rats were randomly divided into 4 groups: sham operation group, ischemia-reperfusion group, 15d-PGJ2 group and 15d-PGJ2+GW9662 group. After reperfusion, serum AST and ALT levels were determined; the liver tissues were removed for measurement of activity of NF-κB and myeloperoxidase (MPO), TNF-α content and expression of ICAM-1. Results Compared with sham operation group, the serum levels of ALT and AST, and the activities of MPO and NF- κ B, TNF- α content and expression of ICAM-1 in ischemia-reperfusion group, 15d-PGJ2 group and 15d-PGJ2+GW9662 group were greatly improved (P ＜ 0.05). Compared with ischemia-reperfusion group, the serum levels of ALT and AST and the activities of MPO and NF- κ B, TNF- α content and expression of ICAM-1 in 15d-PGJ2 group were significantly decreased (P ＜ 0.05). Compared with 15d-PGJ2 group, the serum levels of ALT and AST, and the activities of MPO and NF- κ B, TNF- α content and the expression of ICAM-1 in 15d-PGJ2+GW9662 group were obviously increased (P ＜ 0.05). Conclusion PPAR γ activator 15d-PGJ2 could protect against ischemia-reperfusion injury in rats, with its possible mechanism of inhibiting NF-κB activation and down-regulating TNF-α content and ICAM-1 expression in a PPARγ dependent fashion.
Acute kidney injury (AKI) is characterized by a sudden and rapid decline of renal function and associated with high morbidity and mortality. AKI can be caused by various factors, and ischemia-reperfusion injury (IRI) is one of the most common causes of AKI. An increasing number of studies found out that exosomes of mesenchymal stem cells (MSCs) could alleviate IRI-AKI by the adjustment of the immune response, the suppression of oxidative stress, the reduction of cell apoptosis, and the promotion of tissue regeneration. This article summarizes the effect and mechanism of MSC-derived exosomes in the treatment of renal ischemia-reperfusion injury, in order to provide useful information for the researches on this field.
Objective To summarize the mechanism and research progress of Kruppel-like factor 2 (KLF2) in various liver diseases and related drug development, providing theoretical basis for further mechanism exploration and clinical application. Method The literatures on the mechanism of KLF2 in liver diseases at home and abroad were collected and summarized. Results KLF2 was widely distributed and had various functions in human body, mainly regulating the growth, differentiation and function of endothelial cells, inhibiting pro-inflammatory and pro-thrombotic gene expression, and participating in important physiological processes such as liver inflammation, oxidative stress and thrombosis, and affecting the occurrence and development of various liver diseases. The regulation of KLF2 expression by statins had been widely used in the treatment of liver diseases. Conclusion KLF2 regulates the expression of related molecules through a variety of pathways and affects the functions of various cells in the liver, which is the focus of research on improving liver injury.
ObjectiveTo investigate the effect of post-conditioning with fospropofol disodium on hepatic ischemiareperfusion (I/R) and its possible mechanism in rats.
MethodsForty-eight Sprague-Dawley rats were randomly divided into four groups, including sham group (S), control group (C), propofol group (P) and fospropofol disodium group (F). According to the different periods after reperfusion, each group was further divided into 2-hour and 4-hour reperfusion subgroups respectively (n=6 in each subgroup), named S2h, C2h, P2h, and F2h subgroups and S4h, C4h, P4h, and F4h subgroups. The livers of rats were reperfused after hepatic ischemia for one hour. In the beginning of reperfusion, normal saline was infused intravenously in group S and group C continuously, propofol was infused intravenously in group P continuously, fospropofol disodium was infused continuously in group F. The blood was sampled at the end of ischemia and reperfusion for assay of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The bcl-2 and bax protein contents in liver tissue were detected by immunohistochemical analysis, and liver samples were stained with hematoxylin-eosine for histological observation and damage degree evaluation by counting the proportion of necrosis cells.
ResultsThe activity of ALT and AST, the rate of necrosis cells and the amount of bcl-2 and bax protein after reperfusion in group C, group P and group F were higher than those in group S at matched reperfusion time points (P<0.05). The activity of ALT and AST, the proportion of necrosis cells and bax protein contents decreased in group P and group F, compared with group C at the same reperfusion time points, while the contents of bcl-2 protein were significantly increased (P<0.05).
ConclusionFospropofol disodium can alleviate hepatic injury induced by ischemia-reperfusion in rats, in which the bcl-2 and bax protein may play important roles.
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.
