To investigate the inhibiting effect of β-Aescin on nuclear factor-κB (NF-κB) activation and the expression of tumor necrosis factor-α (TNF-α) protein after traumatic brain injury (TBI) in the rat brain, 62 SD ra...To investigate the inhibiting effect of β-Aescin on nuclear factor-κB (NF-κB) activation and the expression of tumor necrosis factor-α (TNF-α) protein after traumatic brain injury (TBI) in the rat brain, 62 SD rats were subjected to lateral cortical impact injury caused by a free-falling object and divided randomly into four groups: (1) sham operated (Group A); (2) injured (Group B); (3) β-Aescin treatment (Group C); (4) pyrrolidine dithocarbamate (PDTC) treatment (Group D). β-Aescin was administered in Group C and PDTC treated in Group D immediately after injury. A series of brain samples were obtained directly 6h, 24 h and 3 d respectively after trauma in four groups. NF-κB activation was examined by Electrophoretic Mobility Shift Assay (EMSA); the levels of TNF-α protein were measured by radio-immunoassay (RIA); the water content of rat brain was measured and pathomorphological observation was carried out. NF-κB activation, the levels of TNF-α protein and the water content of rat brain were significantly increased (P＜0.01) following TBI in rats. Compared with Group B, NF-κB activation (P＜0.01), the levels of TNF-α protein (P＜0.01) and the water content of brain (P＜0.05) began to decrease obviously after injury in Groups C and D.β-Aescin could dramatically inhibit NF-κB activation and the expression of TNF-α protein in the rat brain, alleviate rat brain edema, and that could partially be the molecular mechanism by which β-Aescin attenuates traumatic brain edema.展开更多
BACKGROUND： L-3-n-butylphthalide （L-NBP） can inhibit phosphorylation of tau protein and reduce the neurotoxicity of beta-amyloid peptide 1-42 （Aβ1-42）. OBJECTIVE： To observe the neuroprotective effects of L-NBP...BACKGROUND： L-3-n-butylphthalide （L-NBP） can inhibit phosphorylation of tau protein and reduce the neurotoxicity of beta-amyloid peptide 1-42 （Aβ1-42）. OBJECTIVE： To observe the neuroprotective effects of L-NBP on caspase-3 and nuclear factor kappa-B （NF- K B） expression in a rat model of Alzheimer＇s disease. DESIGN, TIME AND SETTING： A cell experiment was performed at the Central Laboratory of Provincial Hospital affiliated to Shandong University between January 2008 and August 2008. MATERIALS： L-NBP （purity 〉 98%） was provided by Shijiazhuang Pharma Group NBP Pharmaceutical Company Limited. Aβ1-42, 3-[4,5-dimethylthiazolo-2]-2,5 iphenyltetrazolium bromide （MTT）, and rabbit anti-Caspase-3 polyclonal antibody were provided by Cell Signaling, USA; goat anti-choactase and rabbit anti-NF- kB antibodies were provided by Santa Cruz, USA. METHODS： Primary cultures were generated from rat basal forebrain and hippocampal neurons at 17 or 19 days of gestation. The cells were assigned into five groups： the control group, the Aβ1-42 group （2 μmol/L）, the Aβ1-42 ＋ 0.1 μmol/L L-NBP group, the Aβ1-42 ＋ 1 μ mol/L L-NBP group, and the Aβ1-42 ＋ 10μmol/L L-NBP group. The neurons were treated with Aβ1-42 （2 μmol/L） alone or in combination with L-NBP （0.1, 1, 10 μmol/L） for 48 hours. Cells in the control group were incubated in PBS. MAIN OUTCOME MEASURES： Morphologic changes were evaluated using inverted microscopy, viability using the M-I-I- method, and the changes in caspase-3 and NF- k B expression using Western blot. RESULTS： Induction with Aβ1-42 for 48 hours caused cell death and soma atrophy, and increased caspase-3 and NF- K B expression （P 〈 0.05）. L-NBP blocked these changes in cell morphology, decreased caspase-3 and NF- k B expression （P 〈 0.05）, and improved cell viability, especially at the high dose （P 〈 0.05）. CONCLUSION： AI3^-42 is toxic to basal forebrain and hippocampal primary neurons; L-NBP protects against this toxicity and inhibits the induction of caspase-3 and NF- K B expression.展开更多
Objective To observe the different expression of NF-κBp65 and cyclinD1 during oral carcinogenesis and to analyze the relationship between the abnormal expression of NF-κBp65, cyclinD1, and the occurrence and develop...Objective To observe the different expression of NF-κBp65 and cyclinD1 during oral carcinogenesis and to analyze the relationship between the abnormal expression of NF-κBp65, cyclinD1, and the occurrence and development of oral carcinogenesis. Methods The streptavidin-biotin-peroxidase (S-P) immunohistochemical method was employed to detect the expression of NF-κBp65 and cyclinD1 protein in 38 rat tongue carcinogenesis specimens induced by 4-nitroquinoline 1-oxide. Results With the progress of tongue carcinogenesis, the expression of NF-κBp65, cyclinD1 was up-regulated. In normal, mild epithelial dysplasia, moderate epithelial dysplasia, severe epithelial dysplasia, carcinoma in situ and squamous cell carcinoma (SCC), the positive rate of NF-κBp65 was 20%, 20%, 50%, 62.5%, 50% and 83.33%, respectively. There was significant differences between normal and SCC (P<0.05); while the level of cyclinD1 was 20%, 60%, 62.5%, 87.5%, 100% and 83.33%, respectively. There was significant differences between normal and severe epithelial dysplasia, carcinoma in situ and SCC (P<0.01 or P<0.05). There was a significant correlation between the increased levels of NF-κBp65, cyclinD1 and histopathological grade. The positive expression of NF-κBp65 was also associated with cyclinD1 in SCC (r= 0.7353, P<0.05). Conclusion The up-expression of NF-κBp65 and cyclinD1 protein may be correlated to the occurrence and the development of oral carcinoma; activated NF-κB plays an important role in the overexpression of cyclinD1. Furthermore, NF-κB and cyclinD1 may be the useful biomarker of oral precancerous lesion.展开更多
文摘To investigate the inhibiting effect of β-Aescin on nuclear factor-κB (NF-κB) activation and the expression of tumor necrosis factor-α (TNF-α) protein after traumatic brain injury (TBI) in the rat brain, 62 SD rats were subjected to lateral cortical impact injury caused by a free-falling object and divided randomly into four groups: (1) sham operated (Group A); (2) injured (Group B); (3) β-Aescin treatment (Group C); (4) pyrrolidine dithocarbamate (PDTC) treatment (Group D). β-Aescin was administered in Group C and PDTC treated in Group D immediately after injury. A series of brain samples were obtained directly 6h, 24 h and 3 d respectively after trauma in four groups. NF-κB activation was examined by Electrophoretic Mobility Shift Assay (EMSA); the levels of TNF-α protein were measured by radio-immunoassay (RIA); the water content of rat brain was measured and pathomorphological observation was carried out. NF-κB activation, the levels of TNF-α protein and the water content of rat brain were significantly increased (P＜0.01) following TBI in rats. Compared with Group B, NF-κB activation (P＜0.01), the levels of TNF-α protein (P＜0.01) and the water content of brain (P＜0.05) began to decrease obviously after injury in Groups C and D.β-Aescin could dramatically inhibit NF-κB activation and the expression of TNF-α protein in the rat brain, alleviate rat brain edema, and that could partially be the molecular mechanism by which β-Aescin attenuates traumatic brain edema.
基金Supported by:the Medicine and Health Scientific Research Projects of Shandong Province,No. 2007HZ065
文摘BACKGROUND： L-3-n-butylphthalide （L-NBP） can inhibit phosphorylation of tau protein and reduce the neurotoxicity of beta-amyloid peptide 1-42 （Aβ1-42）. OBJECTIVE： To observe the neuroprotective effects of L-NBP on caspase-3 and nuclear factor kappa-B （NF- K B） expression in a rat model of Alzheimer＇s disease. DESIGN, TIME AND SETTING： A cell experiment was performed at the Central Laboratory of Provincial Hospital affiliated to Shandong University between January 2008 and August 2008. MATERIALS： L-NBP （purity 〉 98%） was provided by Shijiazhuang Pharma Group NBP Pharmaceutical Company Limited. Aβ1-42, 3-[4,5-dimethylthiazolo-2]-2,5 iphenyltetrazolium bromide （MTT）, and rabbit anti-Caspase-3 polyclonal antibody were provided by Cell Signaling, USA; goat anti-choactase and rabbit anti-NF- kB antibodies were provided by Santa Cruz, USA. METHODS： Primary cultures were generated from rat basal forebrain and hippocampal neurons at 17 or 19 days of gestation. The cells were assigned into five groups： the control group, the Aβ1-42 group （2 μmol/L）, the Aβ1-42 ＋ 0.1 μmol/L L-NBP group, the Aβ1-42 ＋ 1 μ mol/L L-NBP group, and the Aβ1-42 ＋ 10μmol/L L-NBP group. The neurons were treated with Aβ1-42 （2 μmol/L） alone or in combination with L-NBP （0.1, 1, 10 μmol/L） for 48 hours. Cells in the control group were incubated in PBS. MAIN OUTCOME MEASURES： Morphologic changes were evaluated using inverted microscopy, viability using the M-I-I- method, and the changes in caspase-3 and NF- k B expression using Western blot. RESULTS： Induction with Aβ1-42 for 48 hours caused cell death and soma atrophy, and increased caspase-3 and NF- K B expression （P 〈 0.05）. L-NBP blocked these changes in cell morphology, decreased caspase-3 and NF- k B expression （P 〈 0.05）, and improved cell viability, especially at the high dose （P 〈 0.05）. CONCLUSION： AI3^-42 is toxic to basal forebrain and hippocampal primary neurons; L-NBP protects against this toxicity and inhibits the induction of caspase-3 and NF- K B expression.
基金Supported by Shanghai Science and Technology Commission,China (03JC14037)
文摘Objective To observe the different expression of NF-κBp65 and cyclinD1 during oral carcinogenesis and to analyze the relationship between the abnormal expression of NF-κBp65, cyclinD1, and the occurrence and development of oral carcinogenesis. Methods The streptavidin-biotin-peroxidase (S-P) immunohistochemical method was employed to detect the expression of NF-κBp65 and cyclinD1 protein in 38 rat tongue carcinogenesis specimens induced by 4-nitroquinoline 1-oxide. Results With the progress of tongue carcinogenesis, the expression of NF-κBp65, cyclinD1 was up-regulated. In normal, mild epithelial dysplasia, moderate epithelial dysplasia, severe epithelial dysplasia, carcinoma in situ and squamous cell carcinoma (SCC), the positive rate of NF-κBp65 was 20%, 20%, 50%, 62.5%, 50% and 83.33%, respectively. There was significant differences between normal and SCC (P<0.05); while the level of cyclinD1 was 20%, 60%, 62.5%, 87.5%, 100% and 83.33%, respectively. There was significant differences between normal and severe epithelial dysplasia, carcinoma in situ and SCC (P<0.01 or P<0.05). There was a significant correlation between the increased levels of NF-κBp65, cyclinD1 and histopathological grade. The positive expression of NF-κBp65 was also associated with cyclinD1 in SCC (r= 0.7353, P<0.05). Conclusion The up-expression of NF-κBp65 and cyclinD1 protein may be correlated to the occurrence and the development of oral carcinoma; activated NF-κB plays an important role in the overexpression of cyclinD1. Furthermore, NF-κB and cyclinD1 may be the useful biomarker of oral precancerous lesion.
