Basic Fibroblast Growth Factor (bFGF) Protects the Blood-Brain Barrier by Binding of FGFR1 and Activating the ERK Signaling Pathway After Intra-Abdominal Hypertension and Traumatic Brain Injury.

BACKGROUND Intra-abdominal hypertension (IAH) is associated with high morbidity and mortality. IAH leads to intra-abdominal tissue damage and causes dysfunction in distal organs such as the brain. The effect of a combined injury due to IAH and traumatic brain injury (TBI) on the integrity of the blood-brain barrier (BBB) has not been investigated. MATERIAL AND METHODS Intracranial pressure (ICP) monitoring, brain water content, EB permeability detection, immunofluorescence staining, real-time PCR, and Western blot analysis were used to examine the effects of IAH and TBI on the BBB in rats, and to characterize the protective effects of basic fibroblast growth factor (bFGF) on combined injury-induced BBB damage. RESULTS Combined injury from IAH and TBI to the BBB resulted in brain edema and increased intracranial pressure. The effects of bFGF on alleviating the rat BBB injuries were determined, indicating that bFGF regulated the expression levels of the tight junction (TJ), adhesion junction (AJ), matrix metalloproteinase (MMP), and IL-1ß, as well as reduced BBB permeability, brain edema, and intracranial pressure. Moreover, the FGFR1 antagonist PD 173074 and the ERK antagonist PD 98059 decreased the protective effects of bFGF. CONCLUSIONS bFGF effectively protected the BBB from damage caused by combined injury from IAH and TBI, and binding of FGFR1 and activation of the ERK signaling pathway was involved in these effects.

Diaphragmatic dysfunction in sepsis due to severe acute pancreatitis complicated by intra-abdominal hypertension.

Objective This study aimed to examine the mechanism of diaphragmatic dysfunction in sepsis due to severe acute pancreatitis (SAP) with intra-abdominal hypertension (IAH) in a rat model. Methods The rats were assigned at random to four groups: (1) control (n = 5), (2) SAP (n = 5), (3) SAP+IAH (n = 5), and (4) SAP+IAH+SS-31 (n = 5). Length and force output of the diaphragm were analysed in vivo. Histopathological examinations were performed by haematoxylin-eosin. Oxidative stress levels related to protease in diaphragmatic mitochondria were detected with a colorimetric technique. Results In the septic rat model due to SAP complicated by IAH, myofibres were increased. Muscle contractile function was significantly lower in the SAP+IAH group compared with the SAP and control groups. Glutathione peroxidase and superoxide dismutase levels were significantly lower and malondialdehyde levels were higher in the SAP and SAP+IAH groups compared with the control group. Notably, SS-31 could reverse atrophy of myofibres in SAP+IAH rats, as well as contractile dysfunction and mitochondrial dysfunction in the diaphragm. Conclusions Diaphragmatic structure and biomechanics are altered in septic rats due to SAP and IAH. This finding is mainly due to an increase in release of mitochondrial reactive oxygen species.

[Influence of haemoxygenase 1 (HO-1) gene expression on intestinal mucosa injury induced by intra-abdominal hypertension in rats].

OBJECTIVE: To observe the effects of up- or down-regulation of haemoxygenase 1 (HO-1) gene expression on intestinal mucosa injury induced by intra-abdominal hypertension (IAH). METHODS: (1) Reproduction of rat model of up- or down-regulation of HO-1 gene expression. Twenty-four healthy adult Wistar rats were divided into Co-PP (HO-1 specific revulsive) 2.5 mg, Co-PP 5.0 mg, Sn-PP (HO-1 specific inhibitor) 2.5 mg, and control groups according to the random number table, with six rats in each group. Rats in groups Co-PP 2.5 mg and Sn-PP 2.5 mg were respectively given Co-PP 2.5 mg/kg and Sn-PP 2.5 mg/kg by intraperitoneal injection, once every 12 hours for 3 days. The rats in group Co-PP 5.0 mg were intraperitoneally injected with Co-PP 5.0 mg/kg, once a day for 3 days. The rats in control group were treated with equal volume of normal saline by intraperitoneal injection. All rats were sacrificed on post injection day (PID) 4, and intestinal mucosa tissues were collected for determination of HO-1 mRNA expression. Optimal dose of Co-PP was chosen for the following experiment. (2) The influence of up- or down-regulation of HO-1 gene expression on intestinal mucosa injury under IAH condition. Another 24 healthy adult Wistar rats were divided into control, IAH, Co-PP+IAH, and Sn-PP+IAH groups according to the random number table, with six rats in each group. The rats in groups Co-PP+IAH and Sn-PP+IAH were intraperitoneally injected with 2.5 mg/kg Co-PP and 2.5 mg/kg Sn-PP, once every 12 hours for 3 days. Equal volume of normal saline was intraperitoneally injected into the rats in control group, once every 12 hours for 3 days. Then, nitrogen gas pneumoperitoneum was used to establish the model of IAH in rats of the latter three groups on PID 4, with IAP at 20 mm Hg (1 mm Hg = 0.133 kPa) , and it was maintained for 2 hours. Puncture and intubation were performed in rats of control group without inflating nitrogen gas. Jejunal segment in the length of 10-15 cm was harvested for collecting intestinal mucosa tissues to determine the HO-1 mRNA expression and diamine oxidase (DAO) content. Serum obtained from portal vein blood was collected to determine the D-lactate, TNF-α, and IL-6 contents. Another jejunal segment in the length of 1-2 cm was harvested for histopathological examination. Data were processed with one-way analysis of variance and t test. RESULTS: (1) The HO-1 mRNA expression in group Co-PP 2.5 mg was significantly higher than that in control and Co-PP 5.0 mg groups (with t values respectively 4.756, 3.175, P < 0.05 or P < 0.01). The HO-1 mRNA expression in group Sn-PP 2.5 mg was significantly lower than that in control group (t = 4.880, P < 0.01). The optimal dose of Co-PP for the following experiment was 2.5 mg/kg. (2) HO-1 mRNA expression in group Co-PP+IAH was 60 ± 5, and it was obviously higher than that of group IAH (49 ± 5, t = 3.811, P < 0.01) and control group (39 ± 4, t = 8.034, P < .001) . HO-1 mRNA expression was higher in group IAH than in control group (t = 3.826, P < 0.01). HO-1 mRNA expression in group Sn-PP+IAH was 29 ± 4, which was obviously lower than that of control group (t = 4.330, P < 0.01). The contents of DAO and D-lactate in group Co-PP+IAH were (0.52 ± 0.05) U/mL and (1.9 ± 0.6) mg/L, which were significantly lower than those in group IAH [(0.88 ± 0.06) U/mL and (4.3 ± 0.7) mg/L, with t values respectively 11.291, 6.376, P values all below 0.01], but still higher than those in control group [(0.34 ± 0.04) U/mL, (1.2 ± 0.5) mg/L, with t values respectively 6.886, 2.295, P < 0.05 or P < 0.01]. The contents of TNF-α and IL-6 were much lower in group Co-PP+IAH than in group IAH, but still higher than in control group (with t values from 3.781 to 18.557, P values all below 0.01). The contents of DAO, D-lactate, TNF-α, and IL-6 in group Sn-PP+IAH were all higher than those in the other 3 groups (with t values from 4.181 to 32.938, P values all below 0.01). Structure of epithelial cells from intestinal mucosa was intact and regularly arranged in rats of control group. Intestinal mucosal tissue was edematous, and the top of villi was anabrotic and necrotic in rats of group IAH. Compared with that of group IAH, the degree of intestinal mucosa injury was alleviated in rats of group Co-PP+IAH, while the pathology was aggravated in rats of group Sn-PP+IAH. CONCLUSIONS: Up-regulation of HO-1 gene expression can ameliorate intestinal mucosa injury caused by IAH, thus protecting intestinal mucosa tissues.

The effects of chronically increased intra-abdominal pressure on the rabbit diaphragm.

BACKGROUND: Diaphragmatic muscular remodeling is caused by various conditions and was mainly studied in pulmonary pathologies and chronic alterations of intra-thoracic pressure. We investigate the effect of the chronically increased intra-abdominal pressure (IAP) on the diaphragm by morphological and biochemical analysis. METHODS: Thirty rabbits were divided into control and study groups. IAP was increased in group B to 12 mmHg for 2 months. The left hemidiaphragm underwent morphological, while the right underwent biochemical analysis. RESULTS: In H&E, all fibers were normal. ATPase analysis demonstrated that type I fibers show no differences between groups. Type ΙΙ(Α) were decreased (p = 0.016) while type ΙΙ(Β/X) fibers were increased (p = 0.025) in group B. Fibers with resistance to fatigue were decreased in group B (p = 0.024). In group B, biochemical activity for glutathione reductase (p = 0.004), glutathione peroxidase (p = 0.021), protein carbonylation (0.029), lipid peroxidation (p = 0.005), and balance of preoxidative-antioxidative factors (p = 0.006) was increased. CONCLUSIONS: Chronically increased IAP induces alterations to the rabbit diaphragm. Adaptation, equivalent to strenuous contraction, transforms the diaphragm to be functionally more efficient toward workload but makes it vulnerable against oxidative stress.

[Experimental study of liver injury in rats of abdominal infection with abdominal compartment syndrome].

OBJECTIVE: To evaluate the liver injury in rats of abdominal infection complicated with abdominal compartment syndrome(ACS). METHODS: SD rats were divided into four groups, including the sham group, the abdominal infection group, the ACS group, and the abdominal infection plus ACS group (combination group). Rats were sacrificed at 1 h, 6 h, 12 h, 24 h after operation with 6 rats at each time point. Blood specimens were collected for liver function testing. Liver tissues were assessed by pathologically examination with hepatic injury severity scoring(HISS). The expressions of Toll-like receptor 4 (TLR4),TNF-α and IL-6 were examined by reverse transcription- polymerase chain reaction. RESULTS: At 24 h after operation, as compared to the sham group(18.2±1.3) U/L and (105.6±25.5) U/L, ALT and AST increased obviously in the abdominal infection group(68.2±17.5) U/L and (184.6±36.1) U/L, the ACS group (305.2±128.2) U/L and (638.0±104.8) U/L and the combination group (409.2±67.1) U/L and (743.2±250.2) U/L, while the combination group had a higher level as compared to the infection group and the ACS group(all P<0.05). HISS scores were significantly higher in the abdominal infection group(5.0), the ACS group(5.5) and the combination group(7.0) as compared to the sham group(1.5), but no significant differences were found among the three groups at 24 h after operation. Expressions of TLR4, TNF-α and IL-6 were significantly higher in combination group than those in the other three groups. CONCLUSIONS: Liver function can be affected by abdominal infection and ACS. Abdominal infection plus ACS results in more severe liver injury.