| It has been proved that Left ventricular hypertrophy (LVH) is an independent risk factor which can lead to cardiovascular diseases besides hypertension. The morbidity of essential hypertension patients with LVH who die of myocardial infarction, heart failure, sudden death and other cardiovascular diseases increases by 6~8 times. The study on pathogenesis, prevention and treatment of LVH have sprung up all over the world in recent years. Cardiac fibroblasts (CFs), the most in heart, are the cell type which chiefly synthesize and secret extracellular matrix(ECM). Collagen is the major component of ECM. At present, it is believed that in EH patients, Myocardial fibrosis, which results from the proliferation of CFs, the elevation of collagen synthesis, overhyperplasia and deposition of collagen, is probably the major pathological factor of LVH. It has confirmed that urotensin II(UII) is a strong mitogen and at present the effects of UII on CFs proliferation and collagen synthesis remain still unknown. The experiment is aimed to explore the effects of UII on CFs proliferation and collagen synthesis and their signalingtransduction mechanism by observing the effects of UII on CFs proliferation and collagen synthesis and the effects of protein kinase C(PKC) blocker, mitogen-activated protein kinase(MAPK)blocker, and calmodulin-dependent protein kinase(CaN) antagonist on Ull-induced CFs proliferation and collagen synthesis, and thus, at the level of cell and molecule it will provide the novel theory evidence for myocardial fibrosis of EH and develop a new method for the prevention and treatment of EH. Experimental contents:The CFs of neonatal Sprague-Dawley(SD) rats cultured with enzymatic dissociation served as a model. Cell number was measured with MTT assay. Cell cycle distribution was determined with flow cytometer(FCM). Immunohistochemisty staining was used to calculate the positive rate of phospho-extracellular signal-regulated kinasel/2(p-ERKl/2). hydroxyproline assay was applied to estimate the content of collagen in CFs supernatant. This study is to observe the effects of UII on CFs proliferation and collagen synthesis, study the regulation effects of PKC blocker chelerythrine(Che), MAPK blocker PD98059 and CaN antagonist cyclosporin A(CsA) on Ull-induced CFs proliferation and collagen synthesis, investigate the relationships between the PKC and CsA signal transduction pathways, and aim to illustrate the signal transduction mechanisms in CFs proliferation and collagen synthesis. Experimental results:(1) With the elevation of UII concentrations, the values of CFs by MTT assay increased gradually and later decreased. The A values of 10-10mol/L, 10-9mol/L and 10-8mol/L UII groups were significantly higher than that of control (p<0.01); while no obvious differenceexisted between 10-7mol/L UII group and control group (p>0.05). (2) the A values of 10-6 mol/L Che+10-8mol/L UII, 10-5mol/L PD98059+10-8mol/L UII and 5 u g/ml CsA+10-8mol/L Un groups by MTT assay were remarkably higher than that of control (p<0.05); while all were notably lower than that of 10-8mol/L UII group (p<0.05). (3) with the elevation of UII concentrations, the collagen contents in CFs supernatant by hydroxyproline assay increased gradually and subsequently decreased. The collagen contents of 10-10mol/L, 10-9mol/L and 10-8mol/L UII groups were significantly higher than that of control (p<0.01); while no obvious difference existed between 10-7mol/L UII group and control group (p>0.05). (4) the collagen contents of 10-6mol/L Che+10-8mol/L UII, 10-5mol/L PD98059+10-8mol/L UII and 5 u g/ml CsA+10-8mol/L UII groups by hydroxyproline assay were remarkably higher than that of control (p<0.01); while all were notably lower than that of 10-8mol/L UII group (p<0.01). (5) with the elevation of UII concentrations, synthesis(S) phase cell percentage and proliferation index(PI) of CFs, incubated with UII for 24 hours, firstly rose and then declined; while G0/G1 phase cell percentage took an opposite tendency. S phase cell percentage and PI of...
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