Objective To investigate influence of genders on the activity of nuclear factor-kappa B (NF-κB) in lungs of endotoxemic rats. Methods Twenty female and 20 male Wistar rats were randomly divided into four groups as follow: female control group (n=10), male control group (n=10), male endotoxemic group (n=10), and female endotoxemic group (n=10). The endotoxemic rats model was made by injecting lipopolysaccharide (5 mg/kg) into the abdominal cavity. Tissue samples were collected from the lungs in different groups and electrophoresis mobility shift assay was used to measure the activity of NF-κB. The levels of serum TNF-α and estrogen were measured at the same time. Results There was no significant difference between the activities of NF-κB in male and female control groups (1.33±0.24 vs 1.47±0.40）, and there was also no significant difference between other items in these groups as well (Pgt;0.05). Yet, the activity of NF-κB (female: 12.10±2.89; male: 19.53±2.12) and the level of TNF-α 〔female: (4.10±0.72) ng/ml; male: (6.37±1.29) ng/ml〕 were significantly increased after injection of lipopolysaccharide (Plt;0.01), and the indices in female group were significantly lower than those in male group (Plt;0.01). Correlation analysis showed that there was a positive relation between the activity of NF-κB in lungs and the level of TNF-α (female: r=0.921 1, P=0.013; male: r=0.907 2, P=0.017), and there was a negative correlation between the activity of NF-κB and the level of estrogen (female: r=-0.887 5, P=0.017; male: r=0.872 3, P=0.022) in both male endotoxemic group and female endotoxemic group (Plt;0.05). Conclusion Gender may be one of the factors that influence the activity of NF-κB in the lungs of endotoxemic rats. While on the other hand, endogenous estrogen may protect the lungs of endotoxemic rats from injury by inhibiting the activity of NF-κB.
Objective To study the expression of nuclear factor-κBp65 (NF-κBp65) in gastric carcinoma and its relationship with vascular endothelial growth factor (VEGF). Methods The expression of NF-κBp65 and VEGF in 56 gastric carcinomas was detected with immunohistochemistry and compared with benign tissues. Results The positive rates of NF-κBp65 and VEGF in 56 gastric carcinomas were 62.5% and 76.8% respectively,and which were higher than those of gastric mucosal atypical hyperplasia (33.3% and 44.4%) and the normal gastric mucosa(0 and 8.3%) （P＜0.05,P＜0.01）.It was found that there was relationship between the expression of NF-κBp65 and the clinical stage, invasion depth of tumor and lymph node metastasis (P＜0.05),but there was no relation to the historica type (Pgt;0.05). There was positive correlation between NF-κBp65 and VEGF expression （r=0.36,P＜0.01）. Conclusion NF-κBp65 may play an important role in the development of gastric carcinoma by up-regulate the expression of VEGF.
ObjectiveTo discuss the role of nuclear factor-kappa B in restenosis after angioplasty.MethodsRelated literatures of recent 5 years were reviewed.ResultsNuclear factor-kappa B could lead to hyperplasia of vascular intima which resulted from proliferation and decrease of apoptosis of vascular smooth muscle cells.ConclusionNuclear factor-kappa B plays an important role in restenosis after angioplasty.
Objective To explore the potential protective effect in vivo of Edaravone, a free radical scavenger on model of acute lung injury in rats with sepsis. Methods Twenty-four male Wistar rats were randomly divided into three groups, ie. a control group( NS group) , a model group( LPS group) , a Edaravone treatment group( ED group) . ALI was induced by injecting LPS intravenously( 10 mg/ kg) in the LPS group and the ED group. Meanwhile the ED group was intravenously injected with Edaravone( 3 mg/ kg) . The NS group was injected with normal saline as control. The lung tissue samples were collected at 6 h after intravenous injection. The wet / dry ( W/D) weight ratio of lung tissue was measured. The levels of myeloperoxidase ( MPO) , malondialdehyde ( MDA ) and superoxide dismutase ( SOD) in lung tissue homogenate were assayed. The pathological changes and expression of nuclear factor-kappa B( NF-κB) in lung tissue were also studied. Results Compared with the NS group, The W/D, pathological scores, NF-κB expression, MPO and MDA levels in the LPS group were significantly higher( all P lt; 0. 01) , and the level of SOD was apparently lower( P lt; 0. 01) . The W/D, pathological scores, NF-κB expression, MPO and MDA levels in the ED group were significantly lower than those in the LPS group( all P lt; 0. 01) and higher than those in the NS group( all P lt; 0. 01) . And the level of SOD in lung tissue of the ED group was higher than that in the LPS group and lower than that in the NS group ( P lt; 0. 01) . Conclusions Edaravone has protective effect on ALI rat model. The mechanismmay be related to its ability of clearing the reactive oxygen species, inhibiting the activation of the signal pathway of NF-κB and inflammatory cascade.
Objective To investigate the protective mechanism of ulinastatin（UTI） in pulmonary microvascular endothelial cells （PMVECs） attacked by serum from the patients with severe sepsis. Methods PMVECs were cultured in vitro and randomly divided into 4 groups，ie. a normal group （culture medium with 10% fetal bovine serum，group N），a health group （culture medium with 10% healthy human serum，group H），a patient group （culture medium with 10% human septic shock serum，group S），and a ulinastatin group （culture medium with 1000 U/mL UTI and 10% human septic shock serum，group U）. The proliferation activity of PMVECs was measured by MTT expressed by optical density （OD）. The concentration of TNF-α in supernatant of culture medium was examined by ELISA at 0，1，2，4，6 hours. The expression of NF-κB was examined by immunohistochemistry at 1 hour. Results Compared with group N，the cell proliferation activity of group S decreased significantly，and the cell proliferation activity of group U decreased slightly at each time poi nt. Compared with group N，the cell proliferation activity of group S and group U at 1，4，6 hours were significant different （Plt;0.05 ）. Compared with group S，the cell proliferation activity of group U at 1，2，6 hours increased significantly （Plt;0.05）. Obviously positive expression of NF-κB in PMVECs could be seen in group S，a little positive expression in group S，and no expression in group N and group H. Compared with group N，the TNF-α levels of group S and group U increased significantly at each time point with significant differences （Plt;0.01）. Compared with group S，the TNF-α levels were significantly reduced at each time point in group U （Plt;0.01）. Conclusions UTI can reduce the release of TNF-α by inhibiting NF-κB activation，thus reduce PMVECs injury attacked by serum from severe sepsis patients.
Objective To observe the protective effect on rat lung by using N-acetyl-L-cysteine(NAC) a inhibiter of nuclear factor-kappa B (NF-κB) in the period of reperfusion. Methods Twenty-four rats were randomly divided into a control group and a trail group.The harvested lung blocks of 12 rats were flushed with and stored in the low-potassium-dextran (LPD) solution at 4℃ for 16 hours. The isolated rat lung reperfusion models were established and the donor lungs were perfused for 1 hour. NAC was used in the trail group but normal saline was used in control group. Partical pressure of oxygen in artery (PaO2), peak airway pressure (PawP) were measured at every 15 min intervals during reperfusion. After reperfusion, the lung tissue wet-to-dry(W/D)ratio, and myeloperoxidase(MPO) activity were obtained. The protein and mRNA expressions of intercellular adhesion molecule-1(ICAM-1), NF-κB were also observed by using immunohistochemistry and semi-quantitative RT-PCR at the end of reperfusion. Results The level of decreased PaO2 and increased PawP in trail group were lower than those in control group at every interval time the sample obtained after reperfusion in 60 min. (Plt;0.01 or lt;0.05). After reperfusion the W/D,MPO, the protein and mRNA expressions of ICAM-1, NF-κB were decreased evidently in trail group than those in control group(Plt;0.01 or lt;0.05). Conclusion Using NAC in the period of reperfusion, can effectively inhibit the expression of NF-κB and ICAM-1,further improve lung respiratory functions.
Objective To review the progress of the mechanisms of Wnt/β-catenin and nuclear factor-kappa B (NF-кB) pathways in the process of the intervertebral disc degeneration. Methods The related literature about the mechanisms of Wnt/β-catenin and NF-кB pathways in the process of the intervertebral disc degeneration was reviewed, analyzed, and summarized. Results Wnt/β-catenin and NF-кB pathways are both activated in the process of the intervertebral disc degeneration, and exist interaction. However, the specific mechanisms and interactive mediums of Wnt/β-catenin and NF-кB pathways in the process of the intervertebral disc degeneration are still unclear. Conclusion The mechanisms of Wnt/β-catenin and NF-кB pathways in the process of the intervertebral disc degeneration have to be studied deeply.
【 Abstract 】 Objective Overexpressions of epidermal growth factor (EGF) and EGF receptor have been associated with progression and invasive phenotype of pancreatic cancer. However, the underlying molecular mechanism by which EGF worked in pancreatic cancer cells has not been completely understood. In this study, effect of EGF on the invasion and metastasis of pancreatic cancer cells and its regulatory mechanism were investigated. Methods The effects of EGF on the proliferation, adhesion and invasion of pancreatic cancer cells were detected by WST-1 proliferation assay, adhesion assay and invasive assay, respectively. The activity and expression of MMP-2 and MMP-9 were examined by zymography, Western blot and RT-PCR, respectively. The activity of NF- κ B was examined by EMSA. Results EGF could significantly promote the invasiveness of pancreatic cancer cells but did not affect cell proliferation or adhesion. The expressions of NF- κ B and MMP-9 were significantly increased by EGF, but EGF did not affect the activity and expression of MMP-2. Furthermore, EGF stimulated the NF- κ B binding activity. Pretreatment with NF- κ B inhibitors, pyrrolidine dithiocarbamate (PDTC), could significantly inhibit the activity of NF- κ B induced by EGF. Meanwhile, the EGF-induced expression and activity of MMP-9, as well as cell invasiveness were also inhibited by NF- κ B inhibitor. Conclusion EGF could increase the expression and promote the invasiveness of MMP-9 via the activation of NF- κ B in pancreatic cancer cells, which implies that NF- κ B inhibitant, such as PDTC, may diminish the invasiveness of pancreatic cancer cells.
Objective To investigate the mechanism of radix salviae miltiorrhizae (RSM) injection in treatment of pancreatitis through observing the changes of activity of nuclear factor-kappa B (NF-κB) in pancreas of rats with severe acute pancreatitis (SAP) and the influence of RSM injection upon NF-κB in pancreas tissue. Methods Seventy-five rats were randomly divided into 3 groups: normal control group, SAP group and RSM treatment group, which were injected with normal saline, normal saline or RSM in the peritoneal cavity, respectively. The model of SAP rats was made by injecting L-arginine into peritoneal cavity and by subcutaneous injection at the same time. The concentrations of amylase in plasma and in ascites were measured respectively, and the expression of NF-κB in pancreas tissues was determined by immunohistochemistry. Results The levels of amylase in plasm and ascites in SAP group and RSM treatment group increased significantly with the increased expression of NF-κB in pancreas tissue, but it was also found that both the level of amylase and the expression of NF-κB in RSM treatment group were significantly lower compared with those in SAP group, and the survival time of RSM treatment group was longer than SAP group with less pathological injury in the pancreas tissues. Conclusion RSM may be effective for the treatment of pancreatitis by degrading the expression of NF-κB.
ObjectiveTo explore the anti-inflammatory mechanism of the proteasome inhibitor MG-132 on rats with acute lung injury (ALI). Methods54 male SD rats were randomly divided into a control group,an ALI group,and a MG-132 group. LPS (5 mg/kg) was injected via tail vein in the ALI group and the MG-132 grouop,while the normal saline was given instead in the control group. MG-132 (10 mg/kg) was injected intraperitoneally at 30 min before LPS administration in the MG-132 group. Six rats in each group were sacrificed at 2,4,and 8h after normal saline or LPS administration. Then the following parameters were observed including pathology changes of lung tissue,wet to dry weight ratio of lung tissue (W/D),the levels of ICAM-1 and TNF-α in bronchoalveolar lavage fluid (BALF) by ELISA,and the protein level of nuclear factor-kappa B P65 (NF-κB P65) in lung tissue by Western blot. ResultsThe pathological observation showed the typical ALI performance,as obvious pulmonary tissue congestion,edema,a large number of inflammatory cells infiltration in the ALI group. These inflammatory performance were obviously alleviated in the MG-132 group. Compared with the control group,the W/D,the levels of ICAM-1 and TNF-α in BALF,and the expression of the protein NF-κB P65 in lung tissue at 2,4 and 6h in the ALI group were significantly increased(P<0.05). Above parameters were significantly decreased in the MG-132 group compared with the ALI group. The expression of the protein NF-κB P65 was significantly positively related with the levels of ICAM-1 and TNF-α in BALF(P<0.01). ConclusionMG-132 can suppress inflammatory response in endotoxin-induced acute lung injury,which may be related to inhibition of NF-κB activation.