Vascular Endothelial Growth Factor In Lung Tissue Research Articles

The establishment and severity assessment of ultrasound-guided prenatal bronchopulmonary dysplasia model in rat

To study a new method for establishing animal models of prenatal bronchopulmonary dysplasia (BPD), we used lung ultrasound score (LUS) to semi-quantitatively assess the severity of lung lesions in model rats. Lipopolysaccharide (LPS) was injected into the right lung of the fetus of the rat under ultrasound-guided, and the right lung of the neonates were scanning for LUS. Specimens were collected for pathological scoring and detection of pulmonary surfactant-associated glycoprotein (SP)-C and vascular endothelial growth factor (VEGF) expression quantity. The correlation between LUS and pathological scores was analyzed. (1) The animal models were consistent with the pathological manifestations of BPD. (2) It showed a strong positive correlation between LUS and pathological scores in animal models (r = 0.84, P < 0.005), and the expression quantity of SP-C and VEGF in lung tissue were decreased (both P < 0.05). Animal models established by ultrasound-guided puncture of the lung of rats and injection of LPS were consistent with the manifestation of BPD. This method could be used to establish animal models of BPD before birth, and the severity of BPD could be assessed by using LUS.

Modulation of Vascular Endothelial Growth Factor and Annexin A2 in Response to 4-(Methylnitrosamino)-1-(3-pyridyl)-1-Butanone -Induced Inflammation via Swimming Training

The nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK; nicotine derived nitrosamine ketone) is one of the strongest carcinogens in tobacco which is involved in induction of lung cancer by changing the stimulation of vascular endothelial growth factor (VEGF) and annexin A2 expression. The aim of this study was to investigate the changes in resting levels of annexin A2 and VEGF in lung tissues of rats exposed NNK after 12 weeks of aerobic submaximal swimming training. For this purpose, 46 Wistar rats were randomly divided into five groups consist of training, training + NNK, NNK, saline and control. NNK-induced groups received NNK subcutaneously one day per week at a rate of 12/5 mg per kg body weight and the training groups performed submaximal swimming training for 12 weeks. The levels of VEGF and annexin A2 in lung tissue were measured respectively by ELISA and immunohistochemistry. To analyze the data; ANOVA and Tukey's test were used at a significance level of p<0.05. Findings indicated that 12 weeks submaximal swimming training decreased the levels of VEGF and annexin A2 in lung tissue significantly when compared to NNK group (p<0.001). There was no significant correlation between VEGF and annexin A2 levels in all study groups (p≥0.05). Generally, it could be confirmed that regular submaximal aerobic training plays an important role in inhibition of the effects of lung inflammation induced by NNK via decreased levels of VEGF and annexin A2.

Effects of aerosol inhalation of recombinant human keratinocyte growth factor 2 on the lung tissue of rabbits with severe smoke inhalation injury

Objective: To investigate the effect of recombinant human keratinocyte growth factor 2 (rhKGF-2) on lung tissue of rabbits with severe smoke inhalation injury. Methods: A total of 120 New Zealand rabbits were divided into 5 groups by random number table after being inflicted with severe smoke inhalation injury, with 24 rats in each group. Rabbits in the simple injury group inhaled air, while rabbits in the injury+phosphate buffer solution (PBS) group inhaled 5 mL PBS once daily for 7 d. Rabbits in injury+1 mg/kg rhKGF-2 group, injury+2 mg/kg rhKGF-2 group, and injury+5 mg/kg rhKGF-2 group received aerosol inhalation of 1 mg/kg, 2 mg/kg, and 5 mg/kg rhKGF-2 (all dissolved in 5 mL PBS) once daily for 7 d, respectively. On treatment day 1, 3, 5, and 7, blood samples were taken from the ear central artery of 6 rabbits in each group. After the blood was taken, the rabbits were sacrificed, and the tracheal carina tissue and lung were collected. Blood pH value, arterial oxygen partial pressure (PaO(2)), arterial blood carbon dioxide pressure (PaCO(2)), and bicarbonate ion were detected by handheld blood analyzer. The expressions of pulmonary surfactant-associated protein A (SP-A) and vascular endothelial growth factor (VEGF) in lung tissue were detected by Western blotting. Pathomorphology of lung tissue and trachea was observed by hematoxylin-eosin staining. Data were processed with analysis of variance of two-way factorial design and Tukey test. Results: (1) Compared with those in simple injury group, the blood pH values of rabbits in the latter groups on treatment day 1-7 had no obvious change (P>0.05). The PaO(2) of rabbits in injury+2 mg/kg rhKGF-2 group on treatment day 5 and 7 were (75.0±2.4) and (71.0±4.5) mmHg (1 mmHg=0.133 kPa), respectively, which were significantly higher than (62.0±6.8) and (63.0±3.0) mmHg in simple injury group (q=4.265, 8.202, P 0.05). The expressions of SP-A in lung tissue of rabbits in injury+2 mg/kg rhKGF-2 group and injury+5 mg/kg rhKGF-2 group on treatment day 3 were 0.091±0.007 and 0.101±0.009, respectively, significantly higher than 0.069±0.009 in simple injury group (q=10.800, 13.580, P 0.05). Compared with those in simple injury group, the expressions of VEGF in lung tissue of rabbits in injury+2 mg/kg rhKGF-2 group on treatment day 3 and 7 were significantly increased (q=4.243, 8.000, P<0.05 or P<0.01), and the expression of VEGF in lung tissue of rabbits in injury+5 mg/kg rhKGF-2 group on treatment day 7 was significantly increased (q=20.720, P<0.01). (4) On treatment day 1, the injury of rabbits in each group was similar, with a large number of neutrophils infiltrated and abscess formed in the alveolar and interstitial tissue, thickened alveolar septum, some collapsed alveolar and atelectasis; large area of tracheal mucosa was degenerated and necrotic, with a large amount of inflammatory exudates blocking in the cavity. On treatment day 3, the inflammation of lung tissue and trachea in each group were improved, but the inflammation in simple injury group and injury+PBS group was also serious. On treatment day 5, the inflammation in lung tissue and trachea of rabbits in injury+2 mg/kg rhKGF-2 group and injury+5 mg/kg rhKGF-2 group were improved much obviously than those in the other groups. On treatment day 7, the inflammation in lung tissue of rabbits in injury+5 mg/kg rhKGF-2 group alleviated obviously than those in the other groups, most alveoli had no obvious exudative fluid, the alveolar cavity was intact and clear, the local alveolar dilated like a cyst, and the alveolar septum thinning; the improvement of inflammation of trachea was more obvious than the other groups, the tracheal mucosa tended to be more complete, and few neutrophils were infiltrated in the endotracheal cavity. Conclusions: Atomization inhalation of rhKGF-2 can improve the PaO(2) level of rabbits with severe smoke inhalation injury, reduce airway inflammation, increase the expression of SP-A and VEGF in lung tissue, thus promoting the repair of lung tissue.

VEGF, Bcl-2 and Bad regulated by angiopoietin-1 in oleic acid induced acute lung injury

Molecular mechanisms of acute lung injury (ALI) are poorly defined. Our previous study demonstrated that recombinant angiopoietin-1 (Ang1) can protect against oleic acid (OA) induced ALI at an early stage. The purpose of this study was to elucidate whether vascular endothelial growth factor (VEGF), Bcl-2, and Bad, phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) play any role in the protective mechanism of recombinant Ang1 in OA-induced ALI. All BALB/C mice were administered a single dose of OA to induce lung injury. Lungs, bronchoalveolar lavage fluid (BALF), and serum were harvested at certain time points. The expression of VEGF, Bcl-2, Bad, PI3K/Akt, and the histological changes in the lung, and the levels of VEGF, IL-6, and IL-10 in serum and BALF were examined. A second cohort of mice was followed for survival for 7days. We observed increased expression of VEGF in BALF and serum and reduced expression of VEGF in lung tissue. Recombinant Ang1 treatment, however, up-regulated VEGF expression and p-Akt/Akt in lung tissue but down-regulated VEGF expression in BALF and serum. OA led to a decrease of anti-apoptotic marker Bcl-2 and a marked increase of pro-apoptotic marker Bad. Compared with the ALI group, in the recombinant Ang1 treated group, Bcl-2 expression was restored, and Bad expression was clearly attenuated. In addition, recombinant Ang1 attenuated the lung pathological changes and improved the survival of mice. These findings suggest that recombinant Ang1 may be a promising potential treatment for ALI. It seems that VEGF is mediated by PI3K/Akt pathway which is required for Ang1-mediated protection of lung injury. Activation of Akt stimulates expression of Bcl-2 and inhibits the expression of Bad, thus inhibiting the execution of apoptosis.

Effects of bone marrow-derived mesenchymal stem cells engraftment on VEGF in lung tissue and in plasma of rabbits at early stage of smog inhalation injury

Objective To discuss the effects of bone marrow-derived mesenchymal stem cells (MSCs) on vascular endothelial growth factor (VEGF) in lung tissue and in plasma, and extra-vascular lung water at the early stage of smog inhalation injury. Method The rabbit model of smog inhalation injury was established by using home-made smog generator, and the rabbit models were randomly(random number) divided into control group (group S, n = 32) and MSCs treatment group (group M, n = 32). Ten mL phosphate-buffered saline (PBS) was injected into ear marginal vein immediately after injury in rabbits of group S. The third generation of MSCs 1/10/10 mL PBS was injected into ear marginal vein immediately after injury in rabbits of group M. The levels of VEGF in peripheral blood and lung tissue were neasured 0 h,2 h,4 h and 6 hours after injection respectively, and analyzed. The right lung of rabbits was taken out to measure and calculate lung water mass fraction after experiment.Results In lung tissue, the levels of VEGF decreased gradually in group S (P ＜ 0.05), and though the levels of VEGF in lung tissue appeared with significant decreasing trend in group M (P ＜ 0.05), they were still higher than those of group S at corresponding intervals ( P ＜ 0.05). In peripheral blood, the levels of VEGF increased gradually in group S ( P ＜ 0. 05), and the levels of VEGF in group M appeared with markedly increasing trend ( P ＜ 0.05),but they were lower significantly than those in group S at corresponding intervals ( P ＜ 0.05). Conclusions MSCs engraftment to the rabbits with smog inhalation injury could increase VEGF in lung tissue, decrease VEGF in plasma and reduce extra-vascular lung water, showing protective effect on smog inhalation injury to a certain extent. Key words: Mesenchymal stem cells; Smoke inhalation injury; Vascular endothelial cell growth factor; Extravascular lung water; Rabbit

Decreased vascular endothelial growth factor expression in lung tissue during acute respiratory distress syndrome

Endothelial injury is an important prognostic factor in acute respiratory distress syndrome (ARDS) [1,2]. Vascular endothelial growth factor (VEGF) plays a critical role in endothelial destruction and angiogenesis [3]. The expression of VEGF in ARDS varies, depending on epithelial and endothelial damage [4,5]. The objective of this study was to investigate the expression of VEGF in lung tissue from ARDS patients.

Dynamic expression of tumor necrosis factor-α and vascular endothelial growth factor in rat model of pulmonary emphysema induced by smoke exposure

In order to explore the roles of tumor necrosis factor-alpha (TNF-alpha) and vascular endothelial growth factor (VEGF) in the pathogenesis of pulmonary emphysema, male Wistar rats were randomized into group A(1), group A(2.5) and group A(4), each with smoke exposure for 1 month, 2.5 months or 4 months, respectively. Group B(1), group B(2.5) and group B(4) were used as non smoking controls at corresponding time points. TNF-alpha in bronchoalveolar lavage fluid (BALF) and expression of VEGF in lung tissue was determined by ELISA or by SABC immunohistochemistry assay either. Lung slices were stained with hematoxylin and eosin (HE). Results showed that in animal with smoke exposure the mean linear interceptor (Lm), an index of pulmonary emphysema and the content of TNF-alpha in BALF increased gradually, on contrary, the expression of VEGF in lung tissue decreased (P<0.05). This phenomenon was not obvious in animals without smoke exposure. Lm was negatively correlated to the VEGF expression (gamma=-0.81, P<0.01) and positively correlated to TNF-alpha concentration (gamma = 0.52, P<0.004), which implies that smoke exposure decreased the expression of VEGF and increased the expression of TNF-alpha. It is plausible to speculate that the imbalance of TNF-alpha and VEGF may play an important role in the pathogenesis of smoke-induced pulmonary emphysema.