RESUMO
OBJECTIVE AND DESIGN: This prospective experimental study aims to investigate whether matrilin-2 is released from burn injury and induces post-burn inflammatory responses as an endogenous danger signal. SUBJECTS: Fifteen burn patients, 15 volunteers, 12 matrilin-2-deficient mice, 36 C57BL/6 mice and raw 264.7 cells. METHODS: Matrilin-2 levels were detected by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction. The inflammatory cytokines production in Matn2 deficient mice and wide type mice were detected by ELISA. Macrophages were activated by recombinant mouse MATN2 with or without adding anti-Toll-like receptor (TLR) 4 antibody. Student's t test and one-way analysis of variance were used for statistical analysis. RESULTS: The matrilin-2 levels in serum of burned patients were drastically elevated as compared to those of healthy controls. The matrilin-2 levels in burned mice were significantly increased than those of non-burned controls, whereas the matrilin-2 mRNA expression was not significantly changed after burn. In addition, Matn2 deficient mice showed remarkably less inflammatory cytokines production and less neutrophil infiltration in lung. Exogenous MATN2 induced potent expression of proinflammatory cytokines production in macrophages, which was inhibited by anti-TLR4 antibody. CONCLUSION: Matrilin-2 induces post-burn inflammatory responses as an endogenous danger signal, partly through a TLR4-mediated mechanism.
Assuntos
Queimaduras/enzimologia , Inflamação/enzimologia , Inflamação/genética , Adulto , Animais , Citocinas/biossíntese , Feminino , Humanos , Inflamação/patologia , Masculino , Proteínas Matrilinas/genética , Proteínas Matrilinas/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Peroxidase/metabolismo , Células RAW 264.7 , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Adulto JovemRESUMO
Background and Aims: Burn and scald injuries are the fourth most common type of trauma. Pediatric burns account for a high proportion of the total number of burn patients and impose a high burden on public health. Understanding the epidemiology of pediatric burns can help improve science education and reduce the incidence of burn injuries. Methods: This study is a single-center retrospective study. One thousand five hundred and twenty-seven pediatric burn patients admitted to our burn center from January 2016 to December 2020 were included. Demographic and epidemiological data of included patients were extracted and analyzed. The correlations of categorical data were tested by the Chi-square tests, and differences of continuous data were tested by the Kruskal-Wallis tests. A p-value of less than 0.05 was considered to be statistically significant. Results: The results showed that children under 3 years of age were most susceptible to burn and scald injuries. Burn injuries were most likely to occur in the season of winter and at the place of home. 56.6% of included patients did receive first aid measures, while 1.8% received gold-standard first aid. Clinical variables related to the severity of injuries were statistically different between patients with and without cooling measures in first aid. Linear regression models showed that emergency treatment of burns in children and adolescents was associated with outcome indicators, including number of operations, total operation duration per total burn surface area (TBSA), cost per TBSA, and length of stay per TBSA. Conclusions: This study summarized the epidemiology and outcomes of pediatric burn patients admitted to a burn center in northern China. Adopting cooling measures in first aid can reduce the severity of injuries and reduce the burden on the medical system. Education on burn prevention and first aid measures to caregivers of children, especially preschool children, should be strengthened.
RESUMO
With the swift evolution of multidrug-resistant bacteria resulting from the intense and inappropriate use of antibiotics, there is a pressing need for innovative solutions. In this study, a thermosensitive hydrogel was developed for efficient bacterial inhibition and promotion of wound healing. The antibacterial chitosan (CS) thermosensitive hydrogel, cross-linked with two-dimensional photothermal nanomaterial black phosphorus (BP) nanosheets through electrostatic interactions, effectively encapsulates and sustains the release of angiogenic drug deferoxamine mesylate (DFO). This facilitates the acceleration of re-epithelialization and neovascularization by enhancing cell migration and proliferation. Following near-infrared (NIR) treatment, this hydrogel demonstrates rapid eradication of the most common multidrug-resistant bacteria encountered in clinical settings, achieved through physical disruption of bacterial membranes and photothermal therapies. Noteworthy is the significant upregulation of IL-19 expression via STAT3 signaling pathways by the BP/CS-DFO hydrogel in a full-thickness wound model. This results in the polarization of the anti-inflammatory M2 macrophage phenotype, altering the microenvironment to a pro-healing state and enhancing extracellular matrix deposition and blood vessel formation. In conclusion, the BP/CS-DFO hydrogel shows immense promise as a potential clinical candidate for wound healing and antimicrobial therapy. Its innovative design and multifunctional capabilities position it as a valuable asset in combating antibiotic resistance and enhancing efficiency in wound healing.
RESUMO
The diaphragm, which is crucial for ventilation, is the primary muscle responsible for inspiration. Patients with severe burns who experience diaphragmatic dysfunction have an increased risk of mortality. Unfortunately, there are currently no effective medications available to prevent or treat this condition. The objective of our study is to utilize bioinformatics to identify potential genes and drugs associated with diaphragmatic dysfunction. In this study, text mining techniques were utilized to identify genes associated with diaphragmatic dysfunction and recovery. Common genes were then analyzed using GO and KEGG pathway analysis, as well as protein-protein interaction (PPI) network analysis. The obtained hub genes were processed using Cytoscape software, and their expression levels in diaphragmatic dysfunction were validated using quantitative real-time polymerase chain reaction (qRT-PCR) in severe burn rats. Genes that were confirmed were then examined in drug-gene interaction databases to identify potential drugs associated with these genes. Our analysis revealed 96 genes that were common to both the "Diaphragm dysfunction" and "Functional Recovery" text mining concepts. Gene enrichment analysis identified 19 genes representing ten pathways. qRT-PCR showed a significant increase in expression levels of 13 genes, including CCL2, CCL3, CD4, EGF, HGF, IFNG, IGF1, IL17A, IL6, LEP, PTGS2, TGFB1, and TNF, in samples with diaphragmatic dysfunction. Additionally, we found that a total of 56 drugs targeted 5 potential genes. These findings provide new insights into the development of more effective drugs for treating diaphragmatic dysfunction, and also present substantial opportunities for researching new target pharmacology and promoting drugs in the pharmaceutical industry.
RESUMO
Burns are characterized by difficult treatment, poor prognosis, and high mortality especially in elderly patients. The aim of this paper is to study the epidemiological and clinical characteristics of elderly burn patients admitted to a major burn center from 2016 to 2020. The data of 471 elderly burn patients admitted to our burn center from January 2016 to December 2020 were retrospectively analyzed. Demographic and clinical variables of different age groups were statistically analyzed, and variables related to length of stay (LOS) and hospitalization costs were analyzed through linear regression models. The mean age of included patients was 69.03 years. Scald injuries accounted for 42.7% of all burns with the extremities being the most commonly affected anatomic site (46.5%). Approximately 67.5% and 5.9% of all patients suffered from full-thickness burns and inhalation injuries, respectively. These patients required more surgical procedures, longer operation durations, and higher costs compared with other burn patients. The mean LOS was 17 days with a mortality rate of 2.1%. There were statistically significant differences in the etiological characteristics and clinical manifestations of burn patients in different age groups. Individualized targeted prevention and treatment strategies should be performed according to the clinical characteristics and relevant risk factors of each patient.
Assuntos
Unidades de Queimados , Queimaduras , Humanos , Idoso , Estudos Retrospectivos , Queimaduras/epidemiologia , Queimaduras/terapia , Hospitalização , Tempo de Internação , China/epidemiologiaRESUMO
Pseudoepitheliomatous hyperplasia (PEH) is a reactive epithelial proliferation secondary to a wide range of stimuli, including traumatic injury, inflammation, infection, and tumors of the skin. PEH secondary to burn injury is rarely reported. We report three cases of PEH patients after burn injury. All three cases were confirmed with the existence of bacterial infection, and all these cases were second- or third-degree burns. All three patients were treated with negative pressure wound therapy after wound debridement or tangential excision. All the wounds healed without split-thickness skin grafting and recurrence.
Assuntos
Queimaduras , Tratamento de Ferimentos com Pressão Negativa , Queimaduras/cirurgia , Queimaduras/terapia , Humanos , Hiperplasia , Transplante de Pele , CicatrizaçãoRESUMO
Background: Hemorrhagic shock is the leading cause of early traumatic death. Research and discussion on restrictive fluid resuscitation have been ongoing for many years. The purpose of this study was to explore whether restrictive resuscitation can inhibit the shedding of vascular endothelial glycocalyx in the prehospital treatment of traumatic hemorrhagic shock pigs. Methods: Landrace pigs were randomly divided into a restrictive resuscitation group (restrictive group) and a conventional resuscitation group (conventional group), with 6 pigs in each group. The gunshot caused a rupture of the pig's receding right femoral artery, and the average arterial pressure was 40-45 mmHg stable for 30 minutes, which was defined as a successful shock model. The end point of resuscitation in the restrictive group was a mean arterial pressure (MAP) of 55-60 mmHg for 30 minutes, and the end point of resuscitation in the conventional group was a MAP of 70-75 mmHg for 30 minutes. The results of arterial blood gas analysis, hemodynamic indicators, endothelial glycocalyx damage and shedding marker Syndecan1 and soluble thrombomodulin (sTM) expression levels were compared between the two groups of experimental pigs after resuscitation. Results: The two groups of experimental pigs had the same baseline levels before injury in age, body weight, blood loss, cardiac output index, cardiac function index (CFI), extravascular lung water index (ELWI), and pulmonary vascular permeability index (PVPI). The arterial blood gas analysis of the two experimental pigs showed no significant difference in carbon dioxide partial pressure, oxygen partial pressure, blood oxygen saturation, or blood lactic acid after resuscitation. The difference in cardiac output index and CFI at the end of resuscitation between the two groups was not statistically significant; the absolute value and percentage of Syndecan1 level increase in the restrictive resuscitation group were lower than those in the conventional resuscitation group, and the difference was statistically significant. Conclusions: Compared with full resuscitation in a short period of prehospital treatment, restrictive resuscitation can achieve a similar effect in maintaining tissue oxygen supply and can reduce the loss of vascular endothelial glycocalyx to a certain extent.
RESUMO
Background: The skin morphological characteristics of the Bama miniature pig are very similar to those of humans; thus, the Bama miniature pig is an ideal choice for establishing a skin burn model. Methods: In this study, 6 ordinary, male, Bama miniature pigs (weight: 23-28 kg and length: 71-75 cm) were used to establish burn models. A mixture of 1 mg of Ketamine and Sumianxin II was used for Bama miniature pigs anesthetizing, and 1 mg of Pentobarbital sodium was added as necessary. The different burn depths were made using a continuous pressure of 1 kg and contact times of 0 s, 10 s, 15 s, 20 s, 25 s, 30 s, 35 s, 40 s, and 45 s by the newly invented electronic burn instrument. The burned tissues were collected and examined with hematoxylin and eosin (H&E) and Masson staining. Results: Burning for 10-15 s caused a first-degree burn; the blood vessels in the superficial dermis were dilated and congested, and necrosis occurred above the basal layer of the epidermis. Burning for 20-25 s caused a superficial partial-thickness burn; the whole epidermal layer was necrotic, and the collagen fibers were slightly deformed. Burning for 30-35 s caused a deep partial-thickness burn; the whole epidermal layer and dermal layers were necrotic with leukocyte infiltration zones, and the collagen fibers were disordered, degenerated, and necrotized. Burning for 40-45 s caused a third-degree burn; the skin layers and adipose tissues were necrotic, and the thick blood vessels in the skin adipose tissues were full of disintegrated and agglutinated red blood cells. Conclusions: Stable burn depth models of Bama miniature pigs were constructed using a new and innovative electronic burn instrument. Our findings provide a basis for further research on the burn mechanism and evaluations of therapeutic drugs.
RESUMO
OBJECTIVE: We aimed to review and discuss some of the latest research results related to post-burn pathophysiological changes and provide some clues for future study. BACKGROUND: Burns are one of the most common and serious traumas and consist of a series of pathophysiological changes of thermal injury. Accompanied by thermal damage to skin and soft tissues, inflammatory mediators are released in large quantities. Changes in histamine, bradykinin, and cytokines such as vascular endothelial growth factor (VEGF), metabolic factors such as adenosine triphosphate (ATP), and activated neutrophils all affect the body's vascular permeability. METHODS: We searched articles with subject words "microvascular permeability", "burn" "endothelium", and "endothelial barrier" in PubMed in English published from the beginning of database to Dec, 2020. CONCLUSIONS: The essence of burn shock is the rapid and extensive fluid transfer in burn and non-burn tissue. After severe burns, the local and systemic vascular permeability increase, causing intravascular fluid extravasation, leading to a progressive decrease in effective circulation volume, an increase in systemic vascular resistance, a decrease in cardiac output, peripheral tissue edema, multiple organ failure, and even death. There are many cells, tissues, mediators and structures involved in the pathophysiological process of the damage to vascular permeability. Ulinastatin is a promising agent for this problem.
RESUMO
BACKGROUND: The choice of treatment methods for children with deep partial-thickness burn wounds (DPBWs) is an issue that requires careful consideration from surgeons. The purpose of this study was to evaluate the efficacy of precise partial scab removal (PPSR) in the treatment of DPBWs in children. METHODS: We retrospectively analyzed the clinical data of 78 children with DPBWs. The children were divided into a PPSR group (n=37) and a routine dressing change (RDC) group (n=41). In the PPSR group, an electric dermatome was used to cut the scab in the early post-injury period. The thickness scale of the electric dermatome was set to 0.1 mm. The scab was removed to the base with scattered bleeding points. There was still a small amount of necrotic tissue in the base of the wound. For the acellular dermal matrix, the first dressing change was about 1 week after surgery. The RDC group was given conventional wound-dressing treatment. The wound dressing was changed with epidermal growth factor, silver-zinc antibacterial cream, and dressing change. The frequency of dressing change was adjusted once a day or once every other day depending on the condition of wound secretions. The hospitalization time, wound-healing time, fever duration, antibiotic use time, number of subsequent operations, and overall hospitalization expenses were compared between the two groups. RESULTS: The wound-healing time of the PPSR group was 19.86±6.4 days, and the wound-healing time of the RDC group was 24.15±7.12 days (P=0.0068). The duration of fever in the PPSR group and RDC group was 2.62±1.99 and 4.44±3.10 days, respectively (P=0.0032). The antibiotic use time in the PPSR group and RDC group was 4.0±1.33 and 4.83±1.88 days, respectively (P=0.0292). The overall hospitalization cost of the PPSR group and RDC group was yuan renminbi ¥37,852.84±10,894.64 and ¥38,047.46±19,450.37, respectively (P=0.9573). CONCLUSIONS: PPSR can shorten wound-healing time, reduce the frequency of dressing changes, shorten the time of fever in children, lower the frequency of antibiotic use, and decrease number of dressing changes on the wound.
RESUMO
BACKGROUND: The diagnosis of burn depth often relies on the subjective judgment of plastic surgeons. Contrast-enhanced ultrasound (CEUS) can visualize the microcirculation well and has potential value in diagnosing the depth of burn wounds. We assessed the depth of the burn wounds by CEUS, and compared the results with histological examination. METHODS: Two rhesus monkeys were used, and multiple burn wounds with different depths were made on their backs. The echo of the dermis and subcutaneous tissue were observed for each wound, and the thickness of the dermis was measured. CEUS was performed to evaluate the depth of burn wounds and compared with pathological results. RESULTS: (I) After scalding, dermal tissue edema occurred, and the thickness of the dermis measured by a US tended to increase gradually, related to the time of scalding and the order of measurement. (II) With the prolongation of the burn time, the depth of filling by contrast agent gradually increased, from the superficial dermis to the deep dermis and subcutaneous tissue, indicating that the depth of tissue damage gradually increased. This was consistent with the pathological observation. The thickness of the healthy dermis was about 1.3-1.8 mm, and 2.7-4.1 mm after scalding. The depth of the burn wounds was 0.9-4.1 mm, accounting for 32-100% of the full skin thickness. CONCLUSIONS: CEUS is a convenient and fast examination method that is consistent with pathological diagnosis of the depth of burn wounds and could prove valuable for the accurate assessment of burn injuries.
RESUMO
OBJECTIVE: To explore the early changes in serum neutrophil elastase (NE) in rats with burn, blast injury or combined burn-blast injury and its significance. METHODS: A total of 176 male Sprague Dawley rats were randomly divided into four groups: control (C), burn (BU), blast injury (BL) and burn-blast combined injury (BB). Rats in C group were not injured. Animals in BU group were subjected to 25% TBSA full-thickness burn on back with 94 degrees C water for 12 seconds; Animals in BL group were inflicted with moderate blast injury with 5 g 8701 compressed dynamite stick as the explosion source 75 cm away while left chest facing the explosive source; Rats in BB group were burned immediately after the blast injury similarly as in BL group. During the first 24 h post-injury, animals in BU and BB groups received intraperitoneal injection of sodium lactate Ringer's solution at a dose of 50 ml x kg(-1) x 12 h(-1). Protein concentration in bronchoalveolar lavage fluid (BALF), water content of lung tissue and NE content in serum were determined at 0 h (C group), 3 h, 6 h, 12 h, 1 d, 2 d, 3 d, 7 d post-injury. RESULTS: Protein concentration in BALF, water content of lung tissue and NE content in serum in SD rats of the injured groups were significantly higher than those in C group (P < 0.01 or P < 0.05), peaked within 2 d post-injury, especially at 2 d post-injury (NE content in serum: BU group, 319. 85 +/- 19.50 ng/ml; BL group, 467.43 +/- 31.64 ng/ml; BB group, 626.00 +/- 26.38 ng/ml vs. C group, 78.53 +/- 25.10 ng/ml). Overall, protein concentration in BALF, water content of lung tissue and NE content in serum in BB group were significantly higher than BU and BL groups (P < 0.01 or P < 0.05). Correlation analysis showed that within 3 d postinjury, a significant positive correlation was found between the protein concentration in BALF, water content of lung tissue and NE content in serum (r = 0.7910, 0.8078, P < 0.05) in BU group. NE content in serum and protein concentration in BALF were significantly positively correlated in BB group (r = 0.8672, P < 0.05). CONCLUSION: NE may play an important role in early lung injury of burn or blast injury, especially in combined burn-blast injury.
Assuntos
Queimaduras/sangue , Elastase de Leucócito/sangue , Lesão Pulmonar/sangue , Ferimentos e Lesões/sangue , Animais , Modelos Animais de Doenças , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
Vascular endothelium dysfunction plays a pivotal role in the initiation and progression of multiple organ dysfunction. The mesenchymal stem cell (MSC) maintains vascular endothelial barrier survival via secreting bioactive factors. However, the mechanism of human umbilical cord MSC (hMSC) in protecting endothelial survival remains unclear. Here, we found IGF-1 secreted by hMSC suppressed severe burn-induced apoptosis of human umbilical vein endothelial cells (HUVECs) and alleviated the dysfunction of vascular endothelial barrier and multiple organs in severely burned rats. Severe burn repressed miR-301a-3p expression, which directly regulated IGF-1 synthesis and secretion in hMSC. Down-regulation of miR-301a-3p decreased HUVECs apoptosis, stabilized endothelial barrier permeability, and subsequently protected against multiple organ dysfunction in vivo. Additionally, miR-301a-3p negatively regulated PI3K/Akt/FOXO3 signaling through IGF-1. Taken together, our study highlights the protective function of IGF-1 against the dysfunction of multiple organs negatively regulated by miR-301a-3p, which may provide the theoretical foundation for further clinical application of hMSC.
RESUMO
BACKGROUND: Hyperglycemia with insulin resistance remains a challenging problem in severely burned patients. Recent studies indicated the involvement of the nucleotide-binding domain and the leucine-rich, repeat-containing family, pyrin-containing 3 (NLRP3) inflammasome in insulin resistance and a beneficial role of apelin in insulin resistance. Our aim was to investigate whether apelin inhibits the activation of the NLRP3 inflammasome and ameliorates insulin resistance in severely burned rats. METHODS: Male Wistar rats were subjected to a full-thickness burn injury comprising 40% of the total body surface area and were randomized to receive apelin, N(G)-methyl-L-arginine acetate salt (L-NMMA), and apelin plus treatments with L-NMMA. The following outcome measurements were assessed: apelin/APJ mRNA expression in white adipose tissue (WAT) and muscles, plasma apelin level, and activation of the NLRP3 inflammasome in WAT, Interleukin-1 ß, interleukin-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1 levels in plasma, insulin resistance, survival rates, and endothelial nitric oxide synthase phosphorylation in soleus muscles. RESULTS: Severe burn induced a decreased expression of apelin/APJ mRNA in soleus muscles and a decrease in plasma apelin levels. Burn injury with apelin treatment restored plasma apelin level, inhibited NLRP3 inflammasome activity in WAT, and decreased inflammatory cytokine levels in plasma. Rats treated with apelin also showed improved insulin sensitivity and decreased mortality, accompanied by a remarkable induction of endothelial nitric oxide synthase phosphorylation in soleus muscle. Furthermore, the aforementioned effects of apelin were inhibited in part by treatment with L-NMMA. CONCLUSION: Apelin inhibits the activation of NLRP3 inflammasome, attenuates systemic inflammatory response, ameliorates insulin resistance, and promotes survival after severe burn, in part through an endothelial nitric oxide synthase-dependent pathway.
Assuntos
Queimaduras/metabolismo , Citocinas/metabolismo , Resistência à Insulina , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , NG-Nitroarginina Metil Éster/farmacologia , Receptores Citoplasmáticos e Nucleares/metabolismo , Análise de Variância , Animais , Apelina , Sítios de Ligação , Queimaduras/mortalidade , Queimaduras/patologia , Proteínas de Transporte , Proteínas do Citoesqueleto/metabolismo , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Teste de Tolerância a Glucose , Inflamassomos/metabolismo , Escala de Gravidade do Ferimento , Peptídeos e Proteínas de Sinalização Intercelular/genética , Estimativa de Kaplan-Meier , Leucina/metabolismo , Masculino , Proteína 3 que Contém Domínio de Pirina da Família NLR , Pirina , Distribuição Aleatória , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase em Tempo Real/métodos , Receptores Citoplasmáticos e Nucleares/genética , Sensibilidade e Especificidade , Estatísticas não Paramétricas , Taxa de SobrevidaRESUMO
While insulin is an anabolic hormone, AMP-activated protein kinase (AMPK) is not only a key energy regulator, but it can also control substrate metabolism directly by inducing skeletal muscle protein degradation. The hypothesis of the present study was that insulin inhibits AMPK and thus down-regulates the expression of the ubiquitin E3 ligases, muscle atrophy F-box (MAFbx) and muscle RING finger 1 (MuRF1) in skeletal muscle cells. Differentiated L6 myotubes were treated with 5-aminoimidazole-4-carboxamide-1-ß-4-ribofuranoside (AICAR) and/or compound C to stimulate and/or block AMPK respectively. These treatments were also conducted in the presence or absence of insulin and the cells were analysed by western blot and quantitative real-time PCR. In addition, nucleotide levels were determined using HPLC. The activation of AMPK with AICAR enhanced the mRNA levels of MAFbx and MuRF1. Insulin reduced the phosphorylation and activity AMPK, which was accompanied by reduced MAFbx and MuRF1 mRNA levels. Using a protein kinase B (PKB/Akt) inhibitor, we found that insulin regulates AMPK through the activation of Akt. Furthermore, insulin down-regulated AMPK α2 mRNA. We conclude that insulin inhibits AMPK through Akt phosphorylation in L6 myotubes, which may serve as a possible signalling pathway for the down-regulation of protein degradation. In addition, decreased expression of AMPK α2 may partially participate in inhibiting the activity of AMPK.
Assuntos
Proteínas Quinases Ativadas por AMP/biossíntese , Regulação para Baixo/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Insulina/farmacologia , Fibras Musculares Esqueléticas/enzimologia , Ubiquitina-Proteína Ligases/biossíntese , Aminoimidazol Carboxamida/análogos & derivados , Animais , Linhagem Celular , Fibras Musculares Esqueléticas/citologia , Proteínas Musculares/metabolismo , Ratos , Ribonucleotídeos/biossíntese , Proteínas Ligases SKP Culina F-Box/metabolismo , Proteínas com Motivo Tripartido , Ubiquitina-Proteína Ligases/metabolismoRESUMO
OBJECTIVE: Neutrophil elastase (NE) takes part in the pathogenesis of acute lung injury. However, its role in lung injury of burn-blast combined injury is unclear. Our objective was to assess the role of NE, and effect of sivelestat, a specific NE inhibitor, in lung injury induced by burn-blast combined injury in rats. METHODS: One hundred and sixty male Sprague-Dawley rats were randomly subjected to burn-blast combined injury (BB) group, burn-blast combined injury plus sivelestat treatment (S) group or control (C) group. Blood gas, protein concentration and NE activity in bronchoalveolar lavage fluid (BALF), pulmonary myeloperoxidase (MPO) activity, serum concentrations of TNF-α and IL-8, etc. were investigated from 0 h to 7 d post-injury. RESULTS: In BB group, PaO2 decreased, while NE activity in BALF, total protein concentration in BALF, pulmonary MPO activity and W/D ratio, serum concentrations of TNF-α and IL-8 increased with neutrophil infiltration, progressive bleeding and pulmonary oedema. Compared with BB group, sivelestat treatment decreased the NE activity and ameliorated the above indexes. CONCLUSION: Sivelestat, exerts a protective effect in lung injury after burn-blast combined injury through inhibiting NE activity to decrease pulmonary vascular permeability, neutrophil sequestration, and production of TNF-α and IL-8.
Assuntos
Traumatismos por Explosões/complicações , Queimaduras/complicações , Elastase de Leucócito/fisiologia , Lesão Pulmonar/enzimologia , Animais , Traumatismos por Explosões/tratamento farmacológico , Traumatismos por Explosões/enzimologia , Líquido da Lavagem Broncoalveolar/química , Queimaduras/tratamento farmacológico , Queimaduras/enzimologia , Dióxido de Carbono/metabolismo , Modelos Animais de Doenças , Glicina/análogos & derivados , Glicina/uso terapêutico , Interleucina-8/metabolismo , Lesão Pulmonar/tratamento farmacológico , Lesão Pulmonar/etiologia , Masculino , Oxigênio/metabolismo , Pressão Parcial , Proteínas Secretadas Inibidoras de Proteinases/uso terapêutico , Ratos , Ratos Sprague-Dawley , Inibidores de Serina Proteinase/uso terapêutico , Sulfonamidas/uso terapêutico , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Burn-blast combined injury has a complex pathological process that may cause adverse complications and difficulties in treatment. This study aims to establish a standard animal model of severe burn-blast combined injury in rats and also to investigate early phasic changes of blood coagulation. By using 54 Wistar rats, distance from explosion source (Hexogen) and size of burned body surface area were determined to induce severe burn-blast combined injury. Thereafter, 256 rats were randomly divided into four groups (n = 64): blast injury group, burn injury group, burn-blast combined injury group, and sham injury group. Gross anatomy and pathological changes in lungs were investigated at 3, 24, 72, and 168 h, respectively. Blood was also collected for analyzing coagulation parameters as prothrombin time, activated partial thromboplastin time, and plasma levels of fibrinogen, D-dimer, antithrombin III, and α2-antiplasmin from 0 to 168 h after injury. Severe burn-blast combined injury was induced by inflicting rats with a moderate blast injury when placing rats 75 cm away from explosion source and a full-thickness burn injury of 25% total body surface area. The rats with burn-blast combined injury had more severe lung injuries when compared with the other three groups. Pathological examination in the BBL group showed diffused alveolar hemorrhage, fluid filling, alveolar atelectasis, rupture and hyperplasia of partial alveolar septum, emphysema-like change, reduced capillary bed, and infiltration of extensive polymorphonuclear cells after injury. The blood of combined injured rats was in a hypercoagulable state within 24 h, shortly restored from 24 to 48 h, and rehypercoagulated from 48 to 72 h after injury. A secondary excessively fibrinolytic function was also found thereafter. The rat model of burn-blast combined injury was successfully established by simulating real explosion characteristics. Rats with burn-blast combined injuries suffered from more severe lung injuries and abnormal coagulation and fibrinolytic function than those induced by a burn injury or a blast injury component. Hence, a time-dependent treatment strategy on coagulation function should be emphasized in clinical therapy of burn-blast combined injury.
Assuntos
Traumatismos por Explosões/sangue , Traumatismos por Explosões/complicações , Coagulação Sanguínea , Queimaduras/sangue , Queimaduras/complicações , Animais , Traumatismos por Explosões/patologia , Queimaduras/patologia , Modelos Animais de Doenças , Fibrinólise , Pulmão/patologia , Lesão Pulmonar/sangue , Lesão Pulmonar/patologia , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: To study the modulatory effect of insulin on apoptosis of skeletal myoblast (L6 cells) by serum of scalded rat and its mechanism. METHODS: L6 cells cultured with DMEM medium containing 10% FBS were divided into control (C, added with 20% normal rat serum), serum from rat with scald injury (S, added with 20% serum from scalded rat), insulin (I, added with 20% normal rat serum and 100 nmol/L insulin), and serum of scalded rat + insulin (SI, added with 20% serum of scalded rat + 100 nmol/L insulin) groups according to the random number table. After being cultured for 48 hours, apoptosis was observed with Hoechst 33258 staining and its number counted, annexin V -FITC/PI double-labeling method was used to assess apoptosis rate, the protein levels of phosphorylated (p-) Akt, p-PI3K, Bax, Bcl-2, and active caspase-3 were determined by Western blotting. Data were processed with grouped or paired t test. RESULTS: (1) The amount of apoptosis with typical morphological change in S group [(59.6 +/- 3.9) per visual field] was more than that in C, I, and SI groups [(4.9 +/- 2.6), (5.5 +/- 2.1), (19.7 +/- 2.3) per visual field, with t value respectively 28.53, 29.86, 21.53, P values all below 0.01]. (2) Apoptotic rate in S group was (18.5 +/- 1.8)%, which was markedly higher than that in C, I, and SI groups [(1.1 +/- 0.6)%, (1.5 +/- 0.3)%, (7.8 +/- 0.6)%, with t value respectively 22.41, 22.83, 13.92, P values all below 0.01]. (3) Compared with those in C group, the protein levels of Bax and active caspase-3 in S group were up-regulated (1.12 +/- 0.63 vs. 0.16 +/- 0.03, 2.15 +/- 0.51 vs. 0.21 +/- 0.03, with t value respectively 3.80, 10.69, P values all below 0.01), the protein level of p-Akt was lowered (0.20 +/- 0.03 vs. 0.42 +/- 0.07, t = -8.46, P < 0.01), and the protein levels of p-PI3K and Bcl-2 showed no statistical difference (0.19 +/- 0.03 vs. 0.26 +/- 0.09, 0.17 +/- 0.03 vs. 0.28 +/- 0.07, with t value respectively -2.73, - 1.14, P values all above 0.05). The protein levels of Bax (0.40 +/- 0.14) and active caspase-3 (0.83 +/- 0.18) in SI group were lowered (t = -3.23, P < 0.05; t = 6.66, P < 0.01) and the protein levels of p-Akt, Bcl-2, and p-PI3K in SI group were elevated (0.39 +/- 0.10, 0.78 +/- 0.03, 0.47 +/- 0.12, with t value respectively 4.07, 18.71, 5.05, P < 0.05 or P < 0.01) as compared with those in S group. CONCLUSIONS: Serum from scalded rat can induce apoptosis in skeletal myoblast, and the effect can be inhibited by insulin through PI3K/Akt signal pathway.
Assuntos
Apoptose/efeitos dos fármacos , Queimaduras/metabolismo , Insulina/farmacologia , Mioblastos Esqueléticos/efeitos dos fármacos , Animais , Queimaduras/sangue , Queimaduras/patologia , Caspase 3/metabolismo , Linhagem Celular , Masculino , Mioblastos Esqueléticos/citologia , Mioblastos Esqueléticos/patologia , Ratos , Ratos Wistar , Soro/imunologia , Transdução de Sinais , Proteína X Associada a bcl-2/metabolismoRESUMO
OBJECTIVE: To explore an appropriate measure to repair tissue defects and deformities in mandibulo-cervical region. METHODS: Eighteen cases with severe tissue defects and deformity in jaw and neck were repaired with thoracic skin flap with multiple blood supply system in our unit from Jan. 2006 to Nov. 2008. Anterior cutaneous branch of transverse cervical artery, intercostal branch of internal thoracic artery and lateral thoracic artery were included in the pedicles. RESULTS: All skin flaps survived, except in one patient in whom a small belb appeared at the distal end of the island flap with anterior cutaneous branch of transverse cervical artery, and it was healed after a few dressing changes. The functions and appearances were satisfactory after 6-month to 2-year follow-up, without showing secondary deformity. CONCLUSIONS: The blood supply of thoracic skin flap is abundant and constant, which is an ideal method for repair of tissue defects and deformities in jaw and neck after taking into account some factors, such as the demand of the patient, general physical condition, and the size of the defect.