Pretreatment with sildenafil alleviates early lung ischemia-reperfusion injury in a rat model

Background

Lung ischemia-reperfusion (I/R) injury plays an important role in lung transplantation. Less well known is the role of sildenafil in lung I/R injury; therefore, we attempted to determine whether sildenafil could alleviate lung apoptosis and tissue injury in a rat model.

Methods

Forty male Sprague-Dawley rats were randomized into four groups: saline + sham, saline + I/R, sildenafil + sham, and sildenafil + I/R groups. Three hours before the operation, each rat received normal saline or sildenafil (10 mg/kg) by lavage. The animals designed to I/R injury were subjected to 2 h of ischemia induced by occlusion of left pulmonary artery, veins, and bronchus, followed by reperfusion for 2 h. The lung tissue was harvested for the analysis of the expression of Bax, Bcl-2, p53, caspase 3, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and wet/dry (W/D) weight ratio.

Results

Compared with the saline + sham group, the saline + I/R group had significant increases in Bax, p53, Bax/Bcl-2 ratio, caspase 3, IL-6, TNF-α, and W/D weight ratio but a decrease in Bcl-2 (P < 0.05). Compared with the saline + I/R group, sildenafil + I/R group had significant decreases in Bax, p53, Bax/Bcl-2 ratio, caspase 3, IL-6, TNF-α level, and W/D weight ratio but an increase in Bcl-2 expression (P < 0.05). Compared with the sildenafil + sham group, there were significant increases in p53 and TNF-α expression in the sildenafil + I/R group (P < 0.05).

Conclusions

Pretreatment with sildenafil alleviates lung apoptosis and tissue injury in a rat model.     

Pioglitazone Attenuates Ischemia/Reperfusion–Induced Liver Injury in Rats

Introduction

Hepatic ischemia/reperfusion (I/R) injury leads to free radical generation and acute inflammatory responses that cause liver damage, an important problem for liver transplantation. Pioglitazone is known to protect I/R injury in various tissues; however, the mechanism of cytoprotection is not well understood. This study investigated the effects of pioglitazone administration in a warm hepatic I/R model on tumor necrosis factor (TNF)-α level, tissue injury, and antioxidant enzyme activity.

Materials and Methods

Eighty wistar strain rats were divided into 4 groups (n = 20): Group 1 sham hosts; Group 2 hepatic I/R; Group 3 hepatic I/R + pioglitazone (10 mg/kg); and Group 4 hepatic I/R + vehicle. Rat livers were subjected to 30 minutes of ischemia followed by 6 hours of reperfusion. After reperfusion rats were humanely killed to obtain liver tissue to study glutathione peroxidase (GPx), superoxide dysmutase (SOD), malondialdehyde (MDA) levels and for histopathologic assessment. TNF-α, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were measured in serum.

Results

Pioglitazone pretreatment significantly reduced liver enzyme content (ALT, 176.80 ± 13.75 vs 235.28 ± 31.92 and AST, 748.20 ± 79.29 vs 944.85 ± 101.87) and TNF-α level (9:8.60 ± 8.67 vs 138.28 ± 9.99) after I/R compared with the control group. MDA level (3.02 ± 0.37 vs 4.36 ± 0.38) and hepatocytic degeneration were reduced in the pioglitazone-treated group. GPx (2.40 ± 0.25 vs 1.36 ± 0.31) and SOD activity (2.22 ± 0.30 vs 1.40 ± 0.35) were significantly higher in the pioglitazone-treated group compared with the control group.

Conclusion

The present study showed that pioglitazone administration improved hepatic I/R injury that was associated with enhanced antioxidant enzyme activities and suppression of TNF-α, ALT, and AST levels. Because peroxisome proliferator-activated receptor-γ agonists are widely used to treat diabetic patients, it may be relatively easy to expand their clinical indication. However, further investigations will be required to delineate protective mechanisms by which pioglitazone attenuates hepatic tissue injury after I/R.     

The effects of ulinastatin on systemic inflammation,visceral vasopermeability and tissue water content in rats with scald injury

Background

The aim of this study was to examine whether administration of ulinastatin inhibits pro-inflammatory mediators and ameliorate visceral vasopermeability both in a rat model of major burn, and also in rat cultured endothelial cells stimulated with permeability-evoking mediators.

Methods

Plasma levels of tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), myeloperoxidase (MPO), microvascular permeability, and water content of organ tissues were evaluated in a rodent model of a 55% TBSA full-thickness scald injury. Microvascular permeability was also evaluated with a cultured pulmonary microvascular endothelial cells (PMECs) monolayer after stimulation with trypsin, bradykinin, histamine, prostaglandin E2 and burn serum.

Results

We found that the plasma levels of TNF-α, CRP, MPO, vascular permeability and water content of heart, lung, kidney, and small intestine tissues were significantly increased in animals after scald injury, and administration of ulinastatin lowered the levels TNF-α, CRP, MPO, vascular permeability and water content of those organ tissues. In vitro, ulinastatin lowered the levels of TNF-α, interleukin-6 (IL-6) and attenuated permeability in PMEC monolayers after being stimulated with burn serum or trypsin, but not by bradykinin, histamine or prostaglandin E2.

Conclusions

These results indicate that ulinastatin attenuates the systemic inflammatory response and visceral vasopermeability both in vivo and vitro, and may serve as a therapeutic agent for prevention of systemic inflammatory response and leakage of fluid into tissue after major burn.     

Tumor necrosis factor-alpha preconditioning attenuates liver ischemia/reperfusion injury through preserving sarco/endoplasmic reticulum calcium-ATPase function

Background

Tumor necrosis factor-alpha (TNF-α) is a multifunctional cytokine. In this study, we investigated the role of TNF-α preconditioning in liver ischemia/reperfusion injury (IRI).

Methods

After IRI, serum alanine aminotransferase, protein levels of SERCA-3, and Caspase-3 in liver were analyzed. In vitro study, primary hepatocytes were isolated from mice and cultured in hypoxic media with or without TNF-α. The levels of SERCA-3, Caspase-3, and intracellular calcium were evaluated after 24-h incubation. In addition, protease inhibitors were adopted to determine the role of SERCA-3 in TNF-α preconditioning.

Results

Low dose of TNF-α preconditioning protected liver from IRI, which was described by reduced serum alanine aminotransferase, Capase-3, and elevated SERCA-3 compared with the animals without TNF-α treatment. The in vitro test confirmed the protective effect of TNF-α through maintaining homeostasis of intracellular calcium. However, the effect of TNF-α was deprived by protease inhibitors.

Conclusions

In this study, we demonstrated that IRI reduced SERCA-3 expression in liver. Low dose of TNF-α preconditioning protected against SERCA-3 reducing, promoted intercellular calcium storage, and attenuated liver IRI.     

Role of neutrophil elastase in lung injury induced by burn–blast combined injury in rats

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.     

Atrial natriuretic peptide attenuates kidney–lung crosstalk in kidney injury

Background

Renal ischemia–reperfusion injury (IRI) is a common cause of acute kidney injury after cardiovascular surgery, which in turn deteriorates oxygenation. Atrial natriuretic peptide (ANP) has natriuretic, diuretic, and anti-inflammatory effects. To elucidate whether renal IRI induces inflammation in the kidney and lung and ANP attenuates kidney–lung crosstalk.

Materials and methods

The rats were anesthetized, tracheostomized, mechanically ventilated, and randomized to four groups: saline + IRI (n = 12), ANP + IRI (n = 12), ANP + sham (n = 6), and saline + sham (n = 6). Saline (6 mL/kg/h) or ANP (0.2 μg/kg/min) at the rate of 6 mL/kg/h was started 5 min before clamping, respectively. Renal IRI was induced by clamping the left renal pedicle for 30 min. The hemodynamics, arterial blood gases, and plasma concentrations of creatinine and lactate were measured at baseline and 1, 2, and 3 h after declamping. Lung wet-to-dry ratio was measured. The mRNA expression of tumor necrosis factor (TNF)-α, interleukin (IL) 1β, and IL-6 and histologic localization of TNF-α in the kidney and lung were measured.

Results

Renal IRI induced metabolic acidosis, pulmonary edema, increases in plasma concentrations of creatinine and lactate, and augmentation of the cytokine mRNA expression and histologic localization of TNF-α in the kidney and Renal IRI induced lung. ANP prevented IRI-induced metabolic acidosis, pulmonary edema, increases in creatinine, lactate, and the cytokine mRNA expression, attenuated histologic localization of TNF-α in the kidney and lung, and increased oxygenation.

Conclusions

ANP has renoprotective and anti-inflammatory effects on the kidney and lung in a rat model of renal IRI, suggesting that ANP attenuates kidney–lung crosstalk.     

Attenuated adiposopathy in perivascular adipose tissue compared with subcutaneous human adipose tissue

Background

We hypothesized that human perivascular and subcutaneous adipose tissues hold distinct phenotypic signatures. We also evaluated the impact of clinical parameters on the adipose phenotype. Our overall goal is to understand the determinants of adipose biology so that this tissue can be manipulated therapeutically to lessen peripheral vascular disease.

Methods

Perivascular and subcutaneous adipose tissues were collected from patients undergoing lower-extremity amputation (n = 27) and protein assayed for proinflammatory mediators (ie, interleukin 6, interleukin 8, leptin, tumor necrosis factor α, monocyte chemoattractant protein-1, and resistin), atheroprotective adiponectin, and the fibrinolysis inhibitor plasminogen activator inhibitor-1.

Results

Leptin (2.7-fold, P = .015), TNF-α (2.2-fold, P = .013), MCP-1 (1.5-fold, P = .047), and adiponectin (1.8-fold, P = .004) were more abundant in subcutaneous vs perivascular adipose tissue. Age positively correlated with perivascular adipose tissue PAI-1 expression (β = .64, P = .042), and hyperlipidemia negatively correlated with perivascular adiponectin (β = −1.18, P = .039).

Conclusions

Human perivascular and subcutaneous adipose tissues hold distinct phenotypic signatures. In amputation patients, the subcutaneous adipose tissue proinflammatory phenotype was relatively attenuated in perivascular adipose tissue.     

Curcumin Attenuates Liver Warm Ischemia and Reperfusion–Induced Combined Restrictive and Obstructive Lung Disease by Reducing Matrix Metalloprotease 9 Activity

Objective

Acute respiratory distress syndrome (ARDS) is a common scenario associated with hepatic warm ischemia and reperfusion (I/R) injury after shock or hemorrhage. Inflammation of lung parenchyma and increase in matrix metalloprotease 9 (MMP-9) activity have been implicated in ARDS. In this study, we aimed to investigate the protective efficacy of curcumin treatment against hepatic I/R–induced lung function impairment.

Methods

Thirty Sprague-Dawley male rats were evenly divided into 3 groups: a sham group, a hepatic I/R group, and a group treated with curcumin (15 mg/kg/d) 15 minutes before ischemia and every 24 hours for the next 48 hours. Ischemia was induced by occluding the hepatic artery and portal vein for 30 minutes. The clamps were then released and the abdominal incision was closed. Pulmonary function test was conducted after 48 hours of reperfusion. We also examined serum alanine transaminase (ALT) level and degrees of tumor necrosis factor α (TNF-α) and MMP-9 activity in the lung tissue.

Results

Hepatic I/R injury decreased the ratio of residual volume to total lung capacity (RV/TLC), chord compliance (Cchord), and maximum midexpiratory flow (MMEF; P < .05), and increased inspiratory resistance (RI; P < .05), characterized as combined obstructive and restrictive lung disease. Treatment with curcumin markedly improved RV/TLC, Cchord, and MMEF and decreased RI (P < .05). In addition, curcumin treatment reduced serum ALT level and degrees of TNF-α level and MMP-9 activity in the lungs.

Conclusions

Curcumin attenuated hepatic I/R–induced combined restrictive and obstructive lung disease by reducing lung inflammation and MMP-9 activity.     

Thalidomide prolongs survival after experimental musculoskeletal injury,through an effect on mononuclear apoptosis

Background

This study was conducted to investigate the effects of intravenous thalidomide administration in an experimental model of musculoskeletal trauma. We hypothesized that because thalidomide inhibits secretion of tumor necrosis factor alpha (TNF-α), survival of animals that received thalidomide would be significantly prolonged.

Material and methods

After an open fracture of the right femur, 24 rabbits were randomly assigned to control and thalidomide groups. Intravenous therapy with thalidomide was started 30 min after fracture. Hemodynamic monitoring of all animals was performed for 4 h. Survival was recorded and bacterial growth in blood and organs was measured after animal death or sacrifice. Blood was sampled for TNF-α measurement and for isolation of peripheral blood mononuclear cells (PBMCs). Apoptosis of PBMCs was measured by flow cytometry.

Results

Survival was significantly prolonged in the thalidomide group. Apoptosis of PBMCs was increased in the control group compared with the thalidomide group at 24 h. There were no differences in vital signs, blood and tissue cultures, and serum TNF-α concentration between the two groups.

Conclusions

Intravenous thalidomide prolonged survival in an experimental model of severe musculoskeletal injury in rabbits. Its mechanism of action did not involve TNF-α suppression but prevention of mononuclear apoptosis. In view of these promising results, further research is needed to clarify the immunomodulatory mechanism of action of thalidomide and its potential use for the management of severe trauma.     

Angelicin regulates LPS-induced inflammation via inhibiting MAPK/NF-κB pathways

Background

Angelicin is a furocoumarin found in Psoralea corylifolia L. fruit. The purpose of this study was to investigate the protective ability of angelicin against inflammation in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and LPS-induced in vivo acute lung injury model.

Materials and methods

The concentrations of tumor necrosis factor alpha (TNF-α) and interleukin (IL)-6 in the culture supernatants of RAW 264.7 cells were determined 24 h after LPS administration. ALI was induced by intratracheal instillation of LPS. Six hours after LPS inhalation, bronchoalveolar lavage fluid and lung tissue samples were obtained for enzyme-linked immunosorbent assay, histologic, and Western blotting analyses.

Results

The results showed that pretreatment with angelicin markedly downregulated TNF-α and IL-6 levels in vitro and in vivo, and significantly decreased the amount of inflammatory cells, lung wet-to-dry weight ratio, and myeloperoxidase activity in LPS-induced ALI mice. Furthermore, Western blotting analysis results demonstrated that angelicin blocked the phosphorylation of IκBα, NF-κBp65, p38 MAPK, and JNK in LPS-induced ALI.

Conclusions

These results suggest that angelicin was potentially advantageous to prevent inflammatory diseases by inhibiting NF-κB and MAPK pathways. Our data indicated that angelicin might be a potential new agent for prevention of inflammatory reactions and diseases in the clinic.     

(Pro)renin receptor blocker improves survival of rats with sepsis

Background

The renin-angiotensin system (RAS) affects inflammatory responses during sepsis. Nonproteolytic activation of prorenin by the (pro)renin receptor has recently been shown to stimulate the tissue RAS. In the present study, the effect of (pro)renin receptor blocker (PRRB) pretreatment on sepsis in a rat cecal ligation and puncture (CLP) model was investigated.

Materials and methods

Male Sprague-Dawley rats underwent CLP and were randomly divided into two groups: PRRB-treated group and control peptide–treated group. Survival was analyzed for 7 d after CLP. The serum concentrations of cytokines and high-mobility group box chromosomal protein 1 (HMGB1) were measured at three time points (0, 3, and 6 h after CLP). Hematoxylin-eosin staining and immunohistochemical staining for nonproteolytically activated prorenin and HMGB1 were performed on the cecum to assess pathologic changes found 6 h after CLP.

Results

Treatment with PRRB improved the survival rate of the post-CLP septic rats (P = 0.023). PRRB also significantly reduced serum tumor necrosis factor-α, interleukin-1β, and HMGB1 levels 6 h after CLP. In CLP rats that were treated with control peptide, the expression of activated prorenin was elevated in peritoneal foam cells. Moreover, expression of HMGB1 was increased in peritoneal inflammatory cells. In contrast, both were markedly suppressed in CLP rats that were treated with PRRB.

Conclusions

PRRB significantly improved the survival rate of rats with clinically relevant sepsis, possibly by attenuating a sepsis-induced systemic inflammatory response. We propose that overactivation of the RAS by activation of prorenin in foam cells may be a significant contributor to sepsis.     

The manner of the inflammation-boosting effect caused by acute hyperglycemia secondary to overfeeding and the effects of insulin therapy in a rat model of sepsis

Background

The aim of the study was to investigate both the inflammation-boosting effect and the metabolic stress induced by acute hyperglycemia secondary to overfeeding with excessive glucose infusion and the effects of insulin therapy on those events in a rat model of sepsis.

Materials and methods

Sprague–Dawley rats underwent cecal ligation and puncture (CLP) or sham operation. Preestablished continuous intravenous glucose infusion was initiated immediately after surgery. First, rats with CLP-inducing sepsis were divided into three groups on the basis of the target blood glucose (BG) levels: high glucose (HG) group (overfed, >300 mg/dL), moderate glucose group (moderate hyperglycemia, 200–300 mg/dL), and no glucose group (100–150 mg/dL). The sham group received the same glucose infusion as that of the HG group. BG and plasma interleukin (IL) 6 levels were monitored over time. All rats were sacrificed 9 h after surgery to evaluate lung histology and measure hepatic total glutathione and malondialdehyde contents. Based on the results, the high glucose and insulin (HI) group was added to septic groups as a model of insulin therapy, in which insulin with the same HG dose as that in the HG group was administered to maintain moderate hyperglycemia.

Results

BG level in all groups remained in the preestablished target range throughout the experiment. Plasma IL-6 level in all septic groups increased in a time-dependent manner, whereas that in the sham group with moderate hyperglycemia hardly increased. Nine hours after CLP, plasma IL-6 level in the HG group rose to 7407.5 ± 1987.3 pg/mL, which was three times higher than that in the other septic groups. There was no significant difference among moderate glucose, no glucose, and HI groups, in which BG level remained constant at <300 mg/dL. The HG group showed the worst consequences of lung injury and oxidative stress in the liver, which were completely stable in HI group.

Conclusions

Acute severe hyperglycemia in critical illness might excessively boost the existing systemic inflammatory response in a threshold-based manner. Insulin therapy under overfeeding could strongly inhibit such a boosting effect and oxidative stress in the liver.     

Deleterious effects of aggressive rapid crystalloid resuscitation on treatment of hyperinflammatory response and lung injury induced by hemorrhage in aging rats

Background

Large-volume, rapid crystalloid infusion may increase endothelial cell damage and induce shear stress, potentially leading to multiple-organ dysfunction syndrome. Limited guideline data for fluid administration are currently available, especially for the aging population. The aim of the present study was to compare the degree of organ damage in conscious aging rats when different resuscitation speeds were used during the treatment of hemorrhagic shock (HS).

Methods

Eighteen aging male Wistar-Kyoto rats were randomly divided into the following three groups: the control group, 30-min rapid resuscitation group, and 12-h slow resuscitation group. To mimic HS, 40% of the total blood volume was withdrawn. Fluid resuscitation (1:3) was given at 30 min after the blood withdrawal. Blood biochemical parameters including glucose, lactic acid, and lactate dehydrogenase (LDH) were measured along with the levels of serum and bronchoalveolar lavage fluid, tumor necrosis factor alpha (TNF-α), and interleukin 10 by enzyme-linked immunosorbent assay. The lungs were examined for pathologic changes, and the injury score at 24 h after HS was calculated.

Results

Compared with slow-rate resuscitation, initially rapid and immediate resuscitation significantly increased the serum levels of glucose, LDH, and proinflammatory cytokines (TNF-α and interleukin 10), and bronchoalveolar lavage fluid levels of white blood cells, TNF-α, and LDH as well as produced pathologic changes in the organ. The lung injury scores were higher after induced HS in aging rats.

Conclusions

The slow and continuous (12 h) fluid resuscitation rate ameliorated HS-induced organ damage in conscious aging rats.     

Dexamethasone effects on vascular flow and organ injury in septic mice

Background

To demonstrate the effects of low-dose dexamethasone treatment on mesenteric artery blood flow, oxidative injury, vascular reactivity, and survival in Swiss albino mice with intra-abdominal polymicrobial sepsis accomplished by cecal ligation and puncture (CLP).

Methods

Mice were allocated to CLP + saline, CLP + dexamethasone, sham + saline, and sham + dexamethasone subgroups to evaluate blood flow, organ injury, and vascular response to consecutive phenylephrine administrations at 24, 48, and 72 h. Survival rates were also evaluated in a different group of mice. Dexamethasone (1 mg/kg/d) and saline (4 mL/kg/d) were administered intraperitoneally to mice 2 h after CLP or sham procedure, whichever appropriate, and repeated once a day until evaluation time at 48 and 72 h. Relaparotomy was performed at the concerned time and mesenteric blood flow was measured, and liver, lung, and peritoneum samples were obtained. Alteration in mesenteric blood flow response to intravenous phenylephrine injections was recorded at the related time intervals in different mice groups. Survival group was followed up by 7-d administration of dexamethasone or saline for 18 d.

Results

The significant fall in mesenteric blood flow after CLP ameliorated with dexamethasone treatment at 48 and 72 h. Dexamethasone also diminished the malonyl dialdehyde level, which is an indicator of organ injury raised after CLP, at 24 h in liver, lung, and peritoneum samples. Dexamethasone therapy has significantly enhanced the vascular response to phenylephrine injections at all doses; however, no change was observed in survival rates.

Conclusions

Low-dose dexamethasone has beneficial effects on mesenteric blood flow and organ injury in experimental sepsis models.     

Gastric Bypass and Sleeve Gastrectomy: the Same Impact on IL-6 and TNF-α. Prospective Clinical Trial

Background

Due to the association between the quantity of adipose tissue and concentrations of interleukin-6 (IL-6) and tumor necrosis factor (TNF-α), this work aimed to assess the effects of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) procedures on serum IL-6 and TNF-α concentrations.

Methods

This study evaluated serum IL-6 and TNF-α levels, as well as routine anthropometric and biochemical values, before and 1 year post-bariatric surgery. Fifty percent of patients (n?=?24) underwent RYGB, and 50 % (n?=?24) underwent SG. Prior to bariatric surgery, IL-6 and TNF-α mRNA expression levels in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were investigated in obese women.

Results

There was a significant reduction (p?<?0.05) in all anthropometric and routine biochemical measurements in patients in the RYGB and SG groups 1 year post-surgery. The serum concentrations of IL-6 and TNF-α were reduced following surgery in both groups (p?<?0.05). No differences in the relative expression levels of IL-6 and TNF-α were found between SAT and VAT prior to bariatric surgery.

Conclusions

RYGB and SG procedures demonstrated a similar impact on adipokine levels in women 1 year post-surgery. Both techniques may improve the course of chronic diseases and the state of inflammation associated with obesity.     

Denervation of capsaicin-sensitive C fibers increases pulmonary inflammation induced by ischemia-reperfusion in rabbits

Background

Capsaicin-sensitive C fibers (CapsCF) are abundantly distributed in the respiratory tract. Inflammation is one of the main contributors to lung ischemia-reperfusion (IR) injury. This study was designed to investigate the role of CapsCF in lung IR-induced inflammatory response.

Methods

Thirty-two male rabbits were randomized into four groups as follows: sham group (S), IR group (IR), large dose of capsaicin plus sham group (CS), and large dose of capsaicin plus IR group (CIR). The CS and CIR groups were pretreated with capsaicin (100 mg/kg) to induce functional ablation of CapsCF. The IR and CIR groups were subjected to 1 h lung ischemia and 3 h reperfusion. Thereafter, blood and lung tissue samples were obtained for blood gas and biochemical analyses. Levels of substance P and calcitonin gene-related peptide (CGRP), lung wet-to-dry weight ratio, and histopathologic changes as well as neutrophil counts in bronchoalveolar lavage fluids were also assessed.

Results

Capsaicin pretreatment in the CIR group resulted in increased lung wet-to-dry ratio, neutrophil counts in bronchoalveolar lavage fluids, and lung pathologic lesions, along with higher levels of plasma tumor necrosis factor α and interleukin 8 and lower level of interleukin 10 (P < 0.05 versus IR), although capsaicin did not alter the above variables in the CS group (P > 0.05 versus S). Lung tissue CGRP was elevated more than 2-fold in the IR group (P < 0.05 versus S), but it did not significantly change in the CIR group.

Conclusion

Denervation of CapsCF aggravated lung IR-induced inflammation, probably by depleting the CGRP content of CapsCF. CapsCF may protect against lung IR-induced inflammation and injury.     

The protective effect of different enteral nutrition combined with growth hormone on intestinal mucosal damage of scalded rats

Objective

To investigate the protective effect of standard enteral nutrition (EN) and enteral immunonutrition (EIN) combined with recombinant human growth hormone rhGH on intestinal mucosa damage in scalded rats.

Methods

Rats subjected to 30% total body surface area (TBSA III°), and they were divided randomly into five groups referred to as EN, EIN, EN + rhGH, EIN + rhGH and control groups. After injury on days 1, 4, 7 and 10, venous blood and intestinal mucus were collected to monitor the level of serum endotoxin, tumor necrosis factor-α (TNF-α) and the concentration of intestinal mucus s-IgA. The number of IgA plasma cells in intestinal tissue and proliferating cell nuclear antigen (PCNA) in intestinal mucosa were detected using the method of immunohistochemistry.

Results

After injury on days 4, 7 and 10, PCNA value of the intestinal mucosa, the number of IgA plasma cells in intestinal lamina and the concentration of intestinal mucus s-IgA in EIN and EN + rhGH groups are significantly increased compared with those in EN group (P < 0.05 or P < 0.01), but serum endotoxin and TNF-α levels are reduced than those in EN group. After injury on days 4, 7 and 10, PCNA values, propria IgA plasma cell number and s-IgA concentration in EIN + rhGH group have no significant difference compared with those in EIN group (P > 0.05), while the serum endotoxin and TNF-α levels are lower than those in EIN group.

Conclusions

EN or EIN combined with rhGH has the additional effect on treatment to reduce intestinal mucosa damage of scalded rats and strengthen the protection of intestinal mucosa damage.     

Effect of vagus nerve stimulation on thermal injury in rats

Objective

To investigate the effects of vagus nerve stimulation on haemodynamics, pulmonary histopathology, arterial blood gas and pro-inflammatory responses to thermal injury.

Interventions

Forty-eight male Sprague–Dawley (SD) rats were randomly divided into six equal groups: normal control (NC) group; thermal injury (TEM) group subjected to 40% total body surface area (%TBSA) third-degree thermal injury; vagotomy (VGX) group subjected to bilateral cervical vagotomy after thermal injury; electrical stimulation (STM) group subjected to bilateral cervical vagotomy plus the left vagus nerve trunk electrical stimulation (5 V, 2 ms and 1 Hz) after thermal injury; the antagonist of muscarinic acetylcholine receptor (MRA) group administrated with atropine (0.1 mg kg⁻¹) before electrical stimulation and the antagonist of nicotinic acetylcholine receptor (NRA) group administrated with hexamethonium (10 mg kg⁻¹) before electrical stimulation.

Measurements and main results

The haemodynamics, histopathology of lung tissue, arterial blood gas, lactic acid, tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels were measured. Vagus nerve electrical stimulation not only significantly increased the mean arterial pressure (MAP) and heart rate (HR), but also decreased the infiltration of inflammatory cells into interstitial and alveolar spaces after thermal challenge and attenuated TNF-α and IL-6 production. Hexamethonium pre-treatment significantly reversed the effects of vagal electrical stimulation, but atropine administration before electrical stimulation had no such effects.

Conclusions

Direct electrical stimulation of the vagus nerve might produce therapeutic effect on thermal injury. The effect may be realised by limiting the inflammatory response via nicotinic acetylcholine receptors in rats.