ABSTRACT
Diabetic cardiomyopathy (DCM), a serious complication of diabetes mellitus, is associated with changes in myocardial structure and function. This study sought to explore the ability of insulin-like growth factor-1 (IGF-1) to modulate DCM and its related mechanisms. Twenty-four male Wistar rats were injected with streptozotocin (STZ, 60 mg/kg) to mimic diabetes mellitus. Myocardial fibrosis and apoptosis were evaluated by histopathologic analyses, and relevant proteins were analyzed by Western blotting. Inflammatory factors were assessed by ELISA. Markers of oxidative stress were tested by colorimetric analysis. Rats with DCM displayed decreased body weight, metabolic abnormalities, elevated apoptosis (as assessed by the bcl-2/bax ratio and TUNEL assays), increased fibrosis, increased markers of oxidative stress (MDA and SOD) and inflammatory factors (TNF-α and IL-1β), and decreased phosphorylation of Akt and glycogen synthase kinase (GSK-3β). IGF-1 treatment, however, attenuated the metabolic abnormalities and myocardial apoptosis, interstitial fibrosis, oxidative stress and inflammation seen in diabetic rats, while also increasing the phosphorylation levels of Akt and GSK-3β. These findings suggest that IGF-1 ameliorates the pathophysiological progress of DCM along with an activation of the Akt/GSK-3β signaling pathway. Our findings suggest that IGF-1 could be a potential therapeutic choice for controlling DCM.
Subject(s)
Animals , Humans , Male , Rats , Apoptosis , Blotting, Western , Body Weight , Diabetes Mellitus , Diabetic Cardiomyopathies , Enzyme-Linked Immunosorbent Assay , Fibrosis , Glycogen Synthase Kinases , In Situ Nick-End Labeling , Inflammation , Insulin-Like Growth Factor I , Oxidative Stress , Phosphorylation , Rats, Wistar , StreptozocinABSTRACT
<p><b>OBJECTIVE</b>To identify the genes differentially expressed among the steroid-resistant nephrotic syndrome (SRNS), steroid-sensitive nephrotic syndrome (SSNS) and normal children, and understand the molecular mechanism of SRNS.</p><p><b>METHODS</b>Affymetrix microarray technology was used to obtain such a profile. The differentially expressed genes among these groups were identified based on signal-to-noise ratios by GCOS software; real-time PCR analysis was performed to confirm the microarray results.</p><p><b>RESULTS</b>There were 157 genes differentially expressed among these groups. The genes up-regulated both in SRNS and SSNS were involved primarily in ionic transportation, immuno-signal transduction and apoptosis. In particular, CLNS1A gene was down regulated in SRNS but up regulated in SSNS.</p><p><b>CONCLUSION</b>Several differentially expressed genes, such as CLNS1A and HLA-DRB4 were found to be closely related to the pathogenesis of SRNS and SSNS. This DNA microarray analysis has provided some important clue to the molecular mechanism of SRNS.</p>
Subject(s)
Child , Humans , Gene Expression Profiling , Gene Expression Regulation , Nephrotic Syndrome , Drug Therapy , Genetics , Steroids , Therapeutic UsesABSTRACT
<p><b>OBJECTIVE</b>To explore the therapeutic effects of the extract of Ginkgo biloba leaf on hypercholestrolemia in children with primary nephritic syndrome (NS).</p><p><b>METHODS</b>Thirty-five children with NS were randomized into 2 groups for treatment with prednisone plus Ginkgo biloba leaf extract (18 cases) or with prednisone plus dipyridamole (17 cases) for 8 weeks. After completion of the treatments, the therapeutic effects were evaluated and the changes in the blood biochemical markers assayed.</p><p><b>RESULTS</b>The 8-week treatment with the extract significantly ameliorated the clinical symptoms and blood biochemistry as compared with prednisone plus dipyridamole group (P<0.01). The levels of urinic protein and blood lipid in Ginkgo leaf group were significantly lower than those in prednisome plus dipyridamole group (P<0.05).</p><p><b>CONCLUSION</b>The extract from Ginkgo biloba leaf can lower blood lipid levels and urinic protein in children with NS and improve their clinical syptoms and the renal function, therefore has much clinical value as an adjuvant treatment of steroid therapy in such children.</p>
Subject(s)
Adolescent , Child , Child, Preschool , Female , Humans , Male , Dipyridamole , Therapeutic Uses , Drug Therapy, Combination , Ginkgo biloba , Chemistry , Glucocorticoids , Therapeutic Uses , Hypercholesterolemia , Blood , Drug Therapy , Lipids , Blood , Nephrotic Syndrome , Phosphodiesterase Inhibitors , Therapeutic Uses , Phytotherapy , Plant Extracts , Therapeutic Uses , Plant Leaves , Chemistry , Prednisone , Therapeutic Uses , Time Factors , Treatment OutcomeABSTRACT
<p><b>OBJECTIVE</b>To observe the effects of fosinopril (FOS) on proliferation and secretion of extracellular matrix of rat glomerular mesangial cell induced by LPS.</p><p><b>METHODS</b>In vitro culture method for glomerular mesangial cells (GMC) of rat was established and passages 3 - 10 of the cells were used in the experiment after identification. The experiment included the following 5 groups: control group (Ctrl), LPS group (LPS), high, medium and low dose FOS groups (FOS1, FOS2 and FOS3 groups, respectively). GMC proliferation was detected by methyl thiazolyl tetrazolium (MTT) incorporation method at 24 and 48 h; the changes of laminin (LN), fibronectin (FN) and ColIV protein secretion was detected by the enzyme-linked immunosorbent assay (ELISA). The changes of LNbeta(2) mRNA expression was detected by semi-quantitative real-time RT-PCR.</p><p><b>RESULTS</b>(1) LPS could induce the mesangial cell proliferation, FOS inhibited this effect of proliferation induced by LPS. (2) Mesangial cells could secrete some extracellular matrix (ECM) protein in normal culture medium, mesangial cell secreted ECM protein was significantly higher in LPS group than that in Ctrl group (P < 0.01), but significantly lower in all FOS groups than that in LPS group (P < 0.01). (3) Mesangial cell could express LNbeta(2) mRNA in normal culture medium, LNbeta(2) mRNA expression was significantly higher in LPS group than that in Ctrl group at all time points, but was significantly lower in FOS group than that in LPS group.</p><p><b>CONCLUSIONS</b>LPS could induce increased secretion of the ECM, including LN, FN, ColIV; FOS could inhibit the secretion of ECM in GMC in a dose-dependent manner at mRNA and protein levels.</p>
Subject(s)
Animals , Rats , Cell Proliferation , Cells, Cultured , Extracellular Matrix Proteins , Bodily Secretions , Fosinopril , Pharmacology , Gene Expression Regulation , Lipopolysaccharides , Mesangial Cells , MetabolismABSTRACT
Objective To observe the effects of fosinopril(FOS),a new generation angiotensin-converting enzyme inhibitor(ACEI),on protein and mRNA expression of transforming growth factor-?_1(TGF-?_1) of rat glomerular mesangial cell(GMC) induced by lipopolysaccharide(LPS);to demonstrate the preventive mechanism against glomerular sclerosis by applying FOS.Methods The cultured GMC in classic way were divided into 3 groups:control group;LPS group;LPS+FOS group.TGF-?_1 concentration in GMC supernatant fluid was detected by ELISA;TGF-?_1 mRNA expression was determined by semiquantitative real-time RT-PCR.Results LPS group was obviously higher than control groups in TGF-?_1 secretion and mRNA expression,while LPS+FOS group decreased distinctively in TGF-?_1 secretion and mRNA expression compared with LPS group.Conclusions FOS has obviously inhibited on TGF-?_1 expression of rat GMC both at protein level and mRNA level,which reveals that it may be an important mechanism by FOS on restraining the development of glomerulosclerosis.