ABSTRACT
In this study, the effect of heparin-derived oligosaccharide (HDO) on bovine vascular smooth muscle cell (VSMC) proliferation and signal transduction mechanism involved were investigated. The levels of PKC-alpha protein and mRNA were determined by cell-based ELISA, RT-PCR, Western blotting and immunocytochemical methods. Meanwhile, mRNA levels of c-jun, c-myc and c-fos were assayed by RT-PCR method. The results showed that HDO inhibited newborn calf serum (NCS)-induced expression of PKC-alpha and proto-oncogenes, which may be one of the mechanisms for the inhibition of VSMC proliferation by HDO. Flow cytometry analysis indicated that HDO blocked NCS-induced cell cycle progression by arresting cells at G0/G1 phase. The results imply that HDO inhibits VSMC proliferation by moderating the gene level of PKC-alpha, eventually inhibiting proto-oncogene mRNA expression and blocking G1/S transition.
Subject(s)
Animals , Cattle , Cell Cycle , Cell Proliferation , Cells, Cultured , G1 Phase , Heparin , Pharmacology , Muscle, Smooth, Vascular , Cell Biology , Metabolism , Oligosaccharides , Pharmacology , Protein Kinase C-alpha , Genetics , Metabolism , Proto-Oncogene Proteins c-fos , Genetics , Metabolism , Proto-Oncogene Proteins c-jun , Genetics , Metabolism , Proto-Oncogene Proteins c-myc , Genetics , Metabolism , RNA, Messenger , Metabolism , Signal TransductionABSTRACT
To investigate the effect of curcumine on acute lung injury induced by oleic acid in rat and the possible mechanism of action. The rats were divided into 6 groups randomly: normal group, control group, curcumine groups (5, 10, 20 mg x kg(-1)) and dexamethasone group (1 mg x kg(-1)). During the experiment, acute lung injury was induced by oleic acid in rat. The changes of dynamic lung compliance were recorded by anrise 2005 pulmonary function test apparatus, light microscope was used to examine histological changes and lung index as well as wet to dry weight ratio was calculated by weighting method. Lung vascular permeability and protein level in BALF were detected by ultraviolet spectrophotometry, and the concentrations of TNF-alpha, IL-6 and IL-10 in BALF were measured by enzyme linked immunosorbent assay (ELISA). The result showed that the changes of pulmonary compliance were inhibited and pulmonary function was improved by curcumine. The OA-induced elevation of lung index was restrained, as well as wet to dry weight ratio, lung vascular permeability, protein level, TNF-alpha (250.4 +/- 21.6 vs. 172.53 +/- 14.88, 122.2 +/- 10.98, 108.69 +/- 3.39) ng x L(-1), IL-6 (763.6 +/- 88.33 vs. 207.41 +/- 15.55, 172.13 +/- 21.91, 142.92 +/- 4.32) ng x L(-1) in BALF in curcumine groups, IL-10 (98.90 +/- 2.99 vs. 208.44 +/- 16.30, 218.43 +/- 6.23, 252.70 +/- 20.58) ng x L(-1) in BALF was increased, respectively significantly. Light microscope findings shown that the impairment in curcumine groups was far less severe than that in model groups. Pretreatment of curcumine showed beneficial effect on acute lung injury induced by oleic acid in rats. The mediation of both proinflammatory factor and anti-inflammatory factor by curcumine may be involved in mechanism of action of curcumine effects.
Subject(s)
Animals , Humans , Male , Rats , Acute Disease , Acute Lung Injury , Drug Therapy , Anti-Inflammatory Agents, Non-Steroidal , Therapeutic Uses , Curcumin , Therapeutic Uses , Drugs, Chinese Herbal , Therapeutic Uses , Oleic Acids , Random Allocation , Rats, Sprague-DawleyABSTRACT
The purpose of this study is to establish COPD animal model by intra-tracheal instillation of bleomycin (BLM) once and exposure to cigarette smoke for continuous 27 d, and to observe the effects of the inhalation on the model. At the 29th day, blood samples were taken from cervical artery for blood-gas analysis and parameters of lung function were recorded. Bronchoalveolar lavage fluid (BALF) was collected to measure intercellular adhesion molecule-1 (ICAM-1) concentration. The results showed that atomization inhaled resveratrol could alleviate rat COPD lung injury accompanied by amelioration of pathological changes, increase the ratio of forced expiratory volume in 0.3 s (FEV0.3) and forced vital capacity (FVC), and decrease the ICAM-1 level in BALF. The ultimate reduction of inflammatory factors was involved, at least in part, in the mechanism of resveratrol effects.
Subject(s)
Animals , Female , Male , Rats , Bleomycin , Blood Gas Analysis , Bronchoalveolar Lavage Fluid , Chemistry , Disease Models, Animal , Forced Expiratory Volume , Intercellular Adhesion Molecule-1 , Metabolism , Lung , Pathology , Lung Compliance , Maximal Midexpiratory Flow Rate , Pulmonary Disease, Chronic Obstructive , Metabolism , Pathology , Random Allocation , Rats, Sprague-Dawley , Smoking , Stilbenes , PharmacologyABSTRACT
Acute lung injury (ALI) makes up a spectrum of disease that is commonly defined as "acute non-cardiogenic edematous lung injury". It may contribute to morbidity and mortality in the critically ill patient in the intensive care unit. ALI was induced by oleic acid in rabbits. During the experiment, blood samples were taken from cervical artery and subjected to blood-gas analysis at different time points after oleic acid injection. Shortly after the rabbits were killed at 3 hour after iv OA injection, bronchoalveolar lavage fluid (BALF) was colleted, and the concentrations of protein, platelet-activating factor (PAF), intercellular adhesion molecule-1 (ICAM-1), interleukin 8 (IL-8) in BALF were then measured by ELISA. The ratio of wet to dry weight (W/D) of left lung was calculated to assess alveolar edema. Lung tissue was fixed in formaldehyde and stained with HE, and examined under a light microscope. The OA-induced elevation of arterial blood oxygen pressure was inhibited, as well as PAF, ICAM-1, IL-8 in BALF in rupatadine group. Furthermore, rupatadine also decreased the concentration of protein in BALF and inhibited the increase of the W/D weight ratio significantly. Light microscopic findings showed that the damage in rupatadine groups was far less severe than that in OA model group. Pretreatment with rupatadine has a beneficial effect on acute lung injury induced by oleic acid in rabbits. The ultimate reduction of inflammatory factors was involved, at least in part, in the mechanism of action of rupatadine effects.
Subject(s)
Animals , Male , Rabbits , Blood Gas Analysis , Bronchoalveolar Lavage Fluid , Chemistry , Cyproheptadine , Pharmacology , Enzyme-Linked Immunosorbent Assay , Intercellular Adhesion Molecule-1 , Metabolism , Interleukin-8 , Metabolism , Lung , Metabolism , Pathology , Oleic Acid , Platelet Activating Factor , Metabolism , Protective Agents , Pharmacology , Random Allocation , Respiratory Distress Syndrome , MetabolismABSTRACT
<p><b>AIM</b>To investigate the effect of iguratimod (T-614), a non-steroidal anti-inflammatory drug, on TNFalpha mRNA expression and TNFalpha production, and on the activity of nuclear factor-kappaB (NF-kappaB) in the rat alveolar macrophage cell line (NR8383) activated by LPS.</p><p><b>METHODS</b>NR8383 cells were pretreated with T-614 (13.4, 26.7, 53.4 micromol x L(-1)), then were stimulated with LPS. The production of TNFalpha in the supernatant of NR8383 was assayed by enzyme-linked immunosorbent assay (ELISA). The TNFalpha mRNA level was determined by a semi-quantitative PCR assay. Assessment of the NF-kappaB DNA binding activity was performed by an ELISA kit.</p><p><b>RESULTS</b>T-614 inhibited LPS-stimulated mRNA expression and production of TNFalpha in a concentration-dependent manner, as well as the activity of NF-kappaB. The IC50 value of effect of T-614 on TNFalpha level was 26.2 micromol x L(-1).</p><p><b>CONCLUSION</b>The inhibitory effect of T-614 on the production of TNFalpha in LPS-stimulated NR8383 cells may be mediated by suppression of NF-kappaB activity.</p>
Subject(s)
Animals , Rats , Anti-Inflammatory Agents, Non-Steroidal , Pharmacology , Cell Line , Cell Proliferation , Chromones , Pharmacology , Lipopolysaccharides , Macrophages, Alveolar , Metabolism , NF-kappa B , Metabolism , RNA, Messenger , Genetics , Sulfonamides , Pharmacology , Tumor Necrosis Factor-alpha , GeneticsABSTRACT
<p><b>AIM</b>To investigate the effect of epigallocatechingallate (EGCG) on acute lung injury induced by oleic acid in mice and the possible mechanism.</p><p><b>METHODS</b>Acute lung injury was induced by oleic acid in mice. Light microscopy and electron microscopy were used to examine histological changes and lung index as well as wet to dry weight ratio was calculated. Serum TNF-a level was measured by enzyme linked immunosorbent assay (ELISA) and the phosphorylation of p38 MAPK was determined by Western blotting.</p><p><b>RESULTS</b>Pretreatment of EGCG significantly alleviated oleic acid induced lung injury accompanied by reduction of lung index and wet to dry weight ratio, decreased of TNF-a level in serum and inhibition of phosphorylation of p38 MAPK.</p><p><b>CONCLUSION</b>EGCG showed beneficial effect on acute lung injury induced by oleic acid in mice. The ultimate reduction of TNF-alpha in serum caused by inhibition of phosphorylated p38 MAPK is involved in the mechanism of action of EGCG.</p>
Subject(s)
Animals , Male , Mice , Catechin , Pharmacology , Lung , Pathology , Oleic Acid , Phosphorylation , Protective Agents , Pharmacology , Respiratory Distress Syndrome , Metabolism , Pathology , Tumor Necrosis Factor-alpha , Metabolism , p38 Mitogen-Activated Protein Kinases , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To study the effect of crocin on rat experimental hyperlipemia and its mechanisms.</p><p><b>METHOD</b>Hyperlipemia model was established by feeding heavy cholesterol for 2 months and the effect of crocin on blood lipid in experimental hyperlipemia rats was observed. Aortic smooth muscle cells were cultured in different culture media and proliferation was measured by MTT assay. Western blotting was used to detect the effect of crocin on phosphorylation of p38 MAPK.</p><p><b>RESULT</b>Crocin not only decreased greatly the content of cholesterol, triglyceride and density lipoprotein in blood, but also increased the content of high density lipoprotein. In addition, the proliferation of smooth muscle cells and the activation of p38MAPK were inhibited by Crocin.</p><p><b>CONCLUSION</b>Crocin prevents atherosclerosis in hyperlipemia, which may be mediated by the inhibition of both proliferation of smooth muscle cells and activation of p38MAPK.</p>