Objective To study the mechanism of alleviating lung ischemia-reperfusion injury by postischemic treatment with namefene hydrochloride, and explore the optimal timing of drug treatment throughout the disease course. Methods A total of 60 rats were randomly divided into six groups with 10 rats in each group: a sham group, a model group, a nalmefene A (NA) group, a nalmefene B (NB) group, a nalmefene C (NC) group and a nalmefene D (ND) group. The sham group without drug treatment was not treated with ischemia-reperfusion. The lung ischemia-reperfusion model was established by occlusion of the left pulmonary hilum in the model group without drug treatment. After ischemic treatment, the NA, NB, NC and ND groups were respectively injected with nalmefene (15 μg/kg) by the tail vein at 5 min before, 10 min, 30 min and 60 min after pulmonary circulation reperfusion. At the 3rd hour after reperfusion, all rats were sacrificed and the specimens from the upper lobe of the left lung tissue were preserved to observe pulmonary lesions, detect wet/dry weight ratio and the activity of myeloperoxidase (MPO), the expressions of tumor necrosis factor-α (TNF-α), Toll-like receptor 2 (TLR2) mRNA and MyD88 mRNA as well as the expressions of TLR2, MyD88, NF-κB p65 and p-NF-κB p65 in lung tissue. Results There were different degrees of alveolar septal destruction, obvious pulmonary interstitial edema, the infiltration of inflammatory cell, the exudationred of blood cell in the mesenchyme, and the collapse of partial alveolar in the model group and the NA, NB, NC, ND groups. In terms of wet/dry weight ratio, the score of lung tissue injury, the activity of MPO, the expressions of TNF-α, TLR2 mRNA and MyD88 mRNA as well as the expressions of TLR2, MyD88, NF-κB p65 and p-NF-κB p65 in lung tissue, the model group were significantly higher than the sham group (P<0.01); there was no significant difference between the ND group and the model group (P>0.05). The corresponding test values of the nalmefene groups with post-ischemic treatment showed the characteristics of ND group> NC group> NB group> NA group (P<0.01). Conclusion The effect of nammefene on alleviating lung ischemia-reperfusion injury is closely related to the inhibition of TLR2, MyD88, NF-κB p65 and phosphorylation of NF-κB p65 with a characteristic of time-dependent manner.
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 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.
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.
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 protective effect of Shenfu injection on liver injury in rats with hind limb ischemia-reperfusion and its mechanism. MethodsSixty-four male rats were randomly divided into sham operation group, ischemia-reperfusion group, Shenfu group〔Shenfu injection 7.5 mL/kg injection of peritoneal(ip), given 10 min before ischemia-reperfusion〕, Shenfu+Znpp group(Shenfu injection 7.5 mL/kg+Znpp 5 mg/kg ip, given 10 min before ischemia-reperfusion), 16 rats in each group. The rat model of hind limb ischemia-reperfusion injury was reproduced by occluding the hind limb artery of the rats for 3 h and subsequent reperfusing for 4 h. The liver tissues were gathered for malondialdehyde(MDA)and superoxide dismutase(SOD)determination. The expression of hemeoxygenase 1(HO-1)protein in the liver tissues was detected by immunohistochemistry. The pathological changes of liver were observed under the light microscope. The changes of serum glutamate-pyruvate transaminase(GPT)and glutamine oxaloacetic transaminase(GOT)were observed respectively. Results①Compared with the sham operation group, the contents of MDA, GPT, GOT, and the expression of HO-1 protein were markedly increased in the ischemia-reperfusion group, Shenfu group, and Shenfu+Znpp group(P < 0.05), the activities of SOD were markedly decreased in the ischemia-reperfusion group and Shenfu+Znpp group(P < 0.05).②Compared with the ischemia-reperfusion group, the contents of MDA, serum GPT, GOT, and the expression of HO-1 protein were markedly decreased, the activity of SOD was markedly increased in the Shenfu group(P < 0.05).③Compared with the Shenfu group, the contents of MDA, GPT, GOT were markedly increased, the activity of SOD was markedly decreased in the Shenfu+Znpp group(P < 0.05). Unde ther light microscope, the pathological changes induced by ischemia-reperfusion were significantly attenuated by the Shenfu injection in the Shenfu group and were reversed by the Znpp in the Shenfu+Znpp group. ConclusionShenfu injection inhibits liver tissue injury during hind limb ischemia-reperfusion, this protective effect might be partly through induction of HO-1.
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.
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).
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.