ABSTRACT
<p><b>OBJECTIVE</b>To assess if the modulating effect of platelet-derived growth factor (PDGF)-BB on p21(WAF1) was mediated by upregulating transforming growth factor (TGF)-beta(1) expression in vascular smooth muscle cells (VSMC).</p><p><b>METHODS</b>TGF-beta(1) mRNA and protein expressions were measured by reverse transcription-PCR and ELISA, the protein expressions of p21(WAF1) and the downstream TGF-beta signalling including TGF-beta type I receptor (ALK-5 in VSMC), Smurf2, pSmad2/3, Smad4, Smad7 were detected by Western blot.</p><p><b>RESULTS</b>PDGF-BB significantly upregulated the expressions of TGF-beta(1) at mRNA (0.79-fold) and protein (1.98-fold) levels in VSMC, significantly inhibited the expression of p21(WAF1) (-67 +/- 12)%, and enhanced the expressions of ALK-5, pSmad2/3, Smad4, Smurf2 protein by 1.21-fold, 0.95-fold, 0.69-fold and 2.55-fold respectively, inhibited Smad7 expression (-65 +/- 9)%, these alterations were partially restored by anti-TGF-beta(1) neutralizing antibody.</p><p><b>CONCLUSIONS</b>These findings suggested that PDGF-BB inhibited p21(WAF1) expression in VSMC partially through upregulating TGF-beta(1) expression via PDGF-BB and TGF-beta signalling pathways.</p>
Subject(s)
Animals , Male , Rats , Cell Division , Cells , Cyclin-Dependent Kinase Inhibitor p21 , Metabolism , Muscle, Smooth, Vascular , Cell Biology , Metabolism , Myocytes, Smooth Muscle , Metabolism , Platelet-Derived Growth Factor , Pharmacology , Proto-Oncogene Proteins c-sis , Rats, Sprague-Dawley , Signal Transduction , Transforming Growth Factor beta1 , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To investigate the protective effects of adiponectin on myocardial ischemia-reperfusion injury and the potential mechanisms in rats.</p><p><b>METHODS</b>Thirty-two male rats aged 8 weeks were randomly assigned to sham operation (sham), myocardial ischemia-reperfusion (MIR), diltiazem treatment (diltiazem) or adiponectin administration (APN) groups (n = 8 each). MIR rats underwent left anterior descending artery (LAD) occlusion for 30 min followed by 60 min reperfusion. Diltiazem (7 microg/g) and APN (120 ng/g) were given by caudal intravenous injection at the end of 30 min ischemia and the beginning of reperfusion for rats in diltiazem or APN groups. Animals were sacrificed after 60 min reperfusion for determining the myocardial nitric oxide (NO), Caspase 3, activity of AMP-activated protein kinase(AMPK) and concentration of peroxisome proliferators-activated receptor gamma (PPARgamma). Apoptotic cells were stained by Caspase 3 Activity Assay Kit and mitochondria in myocardial cells were observed by transmission electron microscope (TEM).</p><p><b>RESULTS</b>The myocardial Caspase 3 level was significantly increased [(168.50 +/- 30.08) micromol/L vs. (53.25 +/- 11.41) micromol/L, P < 0.01], AMPK activity, PPARgamma and NO concentrations were significantly reduced in MIR group compared with those in sham group (all P < 0.05) [(0.74 +/- 0.59) IU/ml vs. (25.63 +/- 4.61) IU/ml, P < 0.01; 0.1894 vs. 0.7949, P < 0.01; (6.359 +/- 1.355) micromol/L vs. (10.396 +/- 1.901) micromol/L, P < 0.01], these effects could be significantly reversed by APN. In comparison with MIR group, the levels of Caspase 3 in cardiac muscles were significantly lowered in Adiponectin group [(88.75 +/- 6.92) micromol/L vs. (168.50 +/- 30.08) micromol/L, P < 0.01], whereas the level of AMPK and PPARgamma, NO concentration in the cardiac muscle was remarkably increased [(27.22 +/- 4.76) IU/ml vs. (0.74 +/- 0.59) IU/ml, P < 0.01; 0.8613 vs. 0.1894, P < 0.01; (15.755 +/- 1.045) micromol/L vs. (6.359 +/- 1.355) micromol/L, P < 0.01]. APN also preserved the function and structure of mitochondria in rats post ischemia/reperfusion injury. The protective pharmacologic actions of APN were superior to that of diltiazem.</p><p><b>CONCLUSION</b>Adiponectin could protect myocardial tissues from myocardial ischemia-reperfusion injury in rats, possibly by upregulating myocardial AMPK and PPARgamma expressions and preventing myocardial cells from apoptosis.</p>
Subject(s)
Animals , Male , Rats , AMP-Activated Protein Kinases , Metabolism , Adiponectin , Pharmacology , Apoptosis , Caspase 3 , Metabolism , Diltiazem , Pharmacology , Myocardial Reperfusion Injury , Metabolism , Myocardium , Metabolism , Nitric Oxide , Metabolism , PPAR gamma , Metabolism , Rats, Sprague-DawleyABSTRACT
<p><b>AIM</b>To study the effect of antidigoxin antiserum on oxygen stress induced by myocardial ischemia/reperfusion (MI/R) injury in rats.</p><p><b>METHODS</b>Sprauge Dawley rats were submitted to ligate left anterior descending coronary artery 30 min followed by 45 min reperfusion. Experiment animals were randomly divided into seven groups including sham group, MI/R group, normal salina group, verapamil group and three antidigoxin antiserum groups from low to high dose. The left ventricular myocardial tissue sample of ischemia were processed and measured the level of endoxin and malondialdehyde (MDA), the activities of Na+, K(+) -ATPase and superoxin dismutase (SOD). The myocardia morphology was observed.</p><p><b>RESULTS</b>The levels of endoxin and MDA increased and the activities of Na+, K(+) -ATPase and MDA were inhibited significantly in MI/R and saline groups. Including verapamil group in comparison to MI/R and saline groups, MDA level decreased and SOD activities partly reserved, meanwhile, only in three antidigoxin antiserum groups, the myocardial endoxin level was remarkably decreased, Na+, K(+) -ATPase activities were drastically increased. The myocardial histological morphology was significantly improved.</p><p><b>CONCLUSION</b>Antidigoxin antiserum, an endoxin mutual clone antibody, had the effect of attenuating the damage of oxygen free radicals induced by MI/R via to antagonizing the inhibition effect of endoxin on myocardial membrane Na+, K(+) -ATPase activities.</p>
Subject(s)
Animals , Rats , Cardenolides , Digoxin , Pharmacology , Immune Sera , Pharmacology , Malondialdehyde , Myocardial Reperfusion , Myocardial Reperfusion Injury , Rats, Sprague-Dawley , Saponins , Sodium-Potassium-Exchanging ATPase , Metabolism , Superoxide Dismutase , MetabolismABSTRACT
Aim To evaluate the protective effect of anti_digoxin antiserum on hypoxic injury myocardium and its mechanism. Methods It was observed that different concentration anti_digoxin antiserum effect on endogenous digitalis_like factor and cell membrane ATPase activity in hypoxic myocardium model. Results The level of endogenous digitalis_like factor was remarkably higher, cell membrane ATPase activity were remarkably lower in hypoxic group than those of normal group; anti_digoxin antiserum can resume membrane ATPase activity.Conclusion Rise of endogenous digitalis_like factor was basic of molecular biology of myocardial damage during myocardial hypoxia. Anti_digoxin antiserum has lightened myocardial injury and has protective effect on hypoxic myocardium by against effect of endogenous digitalis_like factor.
ABSTRACT
Aim The chronic toxicity of tea polyphenols(TP) in dogs was observed. Methods 18 dogs were randomly divided into high, middle and low dose TP groups and one control group . When TP was given(po) by 650 mg?kg-1?d-1,65 mg?kg-1?d-1,6.5 mg?kg-1?d-1 respectively for 90 d and after TP was stopped for two weeks, the general conditions, ECG, blood routine, urine routine, serum lipids, blood sugar, coagulation time, and hepatic and kidney function were detected respectively. Results These mdices were not different from each other among the 4 groups before, during and after administration of TP . The level of serum total cholesterol was progressively decreased in TP groups. Conclusion TP has no toxic effect on dogs and can decrease the level of serum total cholesterol in normal dogs.