ABSTRACT
<p><b>OBJECTIVE</b>To explore roles of extracellular signal-regulated kinase (ERK) 1/2, p38 mitogen activated protein kinase (p38 MAPK) and nuclear factor (NF) -KB in expression of inducible nitric oxide synthase (iNOS) in rat alveolar macrophages induced by high mobility group box 1 (HMGB1 ).</p><p><b>METHODS</b>Primary rat alveolar macrophages (PRAMs) cultured in vitro were incubated with PD98059 ( inhibitor against ERK), SB203580 (inhibitor against p38 MAPK) , PDTC (inhibitor against NF-kappaB), or PD98059 plus SB203580 for 2 hours, respectively. HMGB1 was added into the cultures and incubated with cells for 6 hours. Total RNA of PRAMs was extracted and iNOS mRNA expression was semi-quantified with reverse transcription-polymerase chain reaction ( RT-PCR). Greiss reaction was applied to determine nitrite/nitrate (NO2-/NO3- ) concentration in PRAMs culture supernatants.</p><p><b>RESULTS</b>Expression of iNOS mRNA and NO production in PRAMs culture supernatants were down-regulated by inhibition of ERK or p38 MAPK by PD98059 or SB203580, respectively (P <0. 05). Moreover, inhibition of iNOS expression and NO production was observed after simultaneous pretreatment with PD98059 and SB203580 (P < 0. 05). Expression of iNOS mRNA in PRAMs and NO production in PRAMs culture supernatants were down-regulated by inhibition of NF-kappaB by PDTC (P <0. 05).</p><p><b>CONCLUSION</b>Cellular signal molecules of ERK, p38 MAPK, and NF-kappaB all participate in the expression of iNOS and NO production in PRAMs induced by HMGB1.</p>
Subject(s)
Animals , Male , Rats , Cells, Cultured , Extracellular Signal-Regulated MAP Kinases , Physiology , Flavonoids , Pharmacology , HMGB1 Protein , Pharmacology , Imidazoles , Pharmacology , Macrophages, Alveolar , Metabolism , NF-kappa B , Physiology , Nitric Oxide Synthase Type II , Proline , Pharmacology , Pyridines , Pharmacology , RNA, Messenger , Rats, Sprague-Dawley , Signal Transduction , Thiocarbamates , Pharmacology , p38 Mitogen-Activated Protein Kinases , PhysiologyABSTRACT
Phytoestrogens are bioactive substances existing in natural plants. They have similar molecular structure to those of estrogens. In this article we introduced their classification and sources, and elucidated their effects on heart from aspects involving cardiac function and myocardial electrophysiology. By regulating serum lipid metabolism, arterial vessels, cytokine levels, and coagulation/fibrinolysis system, phytoestrogens possess the effects of anti-atherosclerosis and may be used to prevent and treat cardiovascular diseases.
Subject(s)
Humans , Arteriosclerosis , Cardiovascular Diseases , Hyperlipidemias , Isoflavones , Pharmacology , Phytoestrogens , Pharmacology , PhytotherapyABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of alpha-zearalenol on angiotensin II-induced beta3 integrin mRNA expression in human umbilical vein endothelial cells (HUVECs).</p><p><b>METHODS</b>The mRNA level in integrin beta3 was determined by reverse transcription-polymerase chain reaction. Endothelial NF-kappaB activity was determined by the luciferase activity assay of plasmid NF-kappaB-LUC.</p><p><b>RESULTS</b>The angiotensin II-induced beta3 integrin mRNA expression was inhibited by alpha-zearalenol and 17beta-estradiol (10 nmol/L -1 micromol/L), but not influenced by ICI 182, 780, a pure competitive antagonist for estrogen receptor or a nitric oxide inhibitor Nomega-Nitro-L-arginine methyl ester hydrochloride. Alpha-zearalenol and 17beta-estradiol suppressed the angiotensin II-induced activation of NF-kappaB in endothelial cells.</p><p><b>CONCLUSION</b>Alpha-zearalenol inhibits angiotensin II-induced integrin beta3 mRNA expression by suppressing NF-kappaB activation in endothelial cells.</p>
Subject(s)
Female , Humans , Angiotensin II , Cells, Cultured , Endothelial Cells , Metabolism , Endothelium, Vascular , Metabolism , Estradiol , Pharmacology , Gene Expression Regulation , Integrin beta3 , Genetics , NF-kappa B , Physiology , Nitric Oxide , Phytoestrogens , Pharmacology , RNA, Messenger , Metabolism , Receptors, Estrogen , Zeranol , PharmacologyABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of Xianzhen tablet (XZT, a Chinese patent compound recipe) on advanced glycosylation end products (AGEs) and mRNA expression of AGE-specific cellular receptor (RAGE) in renal cortex of diabetic rats in order to explore the mechanism of XZT in protecting kidney.</p><p><b>METHODS</b>The diabetic rat model with persistent hyperglycemic renal damage was reproduced by streptozotocin. Fluorescent assay and RT-PCR were used to determine the content of AGEs and expression of RAGE mRNA in renal cortex in model rats, which were treated with XZT and controlled by aminoguanidine (AG) administration.</p><p><b>RESULTS</b>The relative content of AGEs and RAGE mRNA expression in renal cortex of model rats 12 weeks after modeling were significantly higher than those in the normal group (P < 0.05), while those in model rats treated by XZT or AG were markedly lower than those in non-treated model rats (P < 0.05), the effect of the both groups showed insignificant difference (P > 0.05).</p><p><b>CONCLUSION</b>XZT could reduce the accumulation of AGEs in renal cortex of diabetic rats, down-regulate the over-expression of RAGE mRNA, with the effects similar to that of AG, the inhibition of XZT on protein non-enzymatic glycosylation might be one of the mechanisms of its effect in protecting kidney.</p>
Subject(s)
Animals , Male , Rats , Diabetes Mellitus, Experimental , Genetics , Metabolism , Pathology , Diabetic Nephropathies , Genetics , Metabolism , Pathology , Down-Regulation , Drugs, Chinese Herbal , Pharmacology , Glycation End Products, Advanced , Genetics , Kidney Cortex , Metabolism , RNA, Messenger , Genetics , Rats, Wistar , Receptor for Advanced Glycation End Products , Receptors, Immunologic , Genetics , TabletsABSTRACT
<p><b>OBJECTIVE</b>To investigate whether acute lung injury (ALI) and changes of myocardial ATP enzymes were induced by intravenous or intraventricle of left heart injection of lipopolysaccharide (LPS) in aging rats.</p><p><b>METHODS</b>40 male Wistar rats were used for reproducing aging animal model. Aging rats were randomly divided into aging control group (n = 8), ALI group (LPS, 5 mg/kg body weight intravenous injection, n = 16), and LPS group (same dosage LPS, intraventricle of left heart injection, n = 16). The samples (blood, lung and heart) were collected at 2, 6 hours after LPS or saline administration.</p><p><b>RESULTS</b>Compared with aging control, protein content in bronchial alveolar lavage fluid (BALF), ratio of lung wet/dry weight and the LA, NO2-/NO3- and MDA contents in blood were increased markedly (P < 0.01) at 2, 6 hours in ALI group. The GSH-Px, Na(+)-K(+)-ATPase activities in lung tissue were decreased significantly (P < 0.01), but NO2-/NO3- content in lung tissue was increased obviously (P < 0.01) at 2 hours in ALI group. These changes were maintained until at 6 hours after LPS administration. The above parameters were no obviously changes in myocardium at 2 hours after LPS administration in ALI group. But at 6 hours, MDA content was increased obviously (P < 0.01); Na(+)-K(+)-ATPase, Ca(2+)-Mg(2+)-ATPase and GSH-Px activities in myocardium were decreased markedly (P < 0.01). While in LPS group, only NO2-/NO3- contents were increased (P < 0.05) in blood and lung tissue as well as Na(+)-K(+)-ATPase activity in lung tissue were decreased (P < 0.05), another parameters had no obvious changes.</p><p><b>CONCLUSIONS</b>ALI was obviously formed by intravenous injection LPS after 2, 6 hours in aging rats. Myocardial enzyme etc decreased only at 6 hours in ALI group. But above parameters were no obviously changes in LPS group. It was suggested that there was probable myocardial damage in rats of ALI group, and it was mainly induced by ALI.</p>