| Backgroud Cardiac fibrosis is one of important pathological changes in the hypertensive heart remodeling. It has been proven that cardiac fibrosis can lead to decreased ventricular compliance, increased ventricular wall stiffness and heart dysfuction. Recent study suggested that hypertensive cardiac fibrosis is associated with monocytes infiltration around the coronary artery and in the myocardial interstitial. It is not known what is the role of inflammation reaction in the hypertensive myocardial fibrosis yet. Mononuclear chemotaxis protein-l(MCP-l) is one of CC chemotaxis protein. It has special chemotaxis to the monocytes. MCP-1 may be one of sources that lead to the monocytes infiltration. Transforming growth factor-p(TGF-P) plays an important role in various tissue fibrosis. Monocyte is one kind of cell that releases TGF-p. Nuclear transcript factor-KB(NF-kB) mediates multi-tissue inflammation. Effects of NF-kB on the cardiac fibroblast releasing MCP-1 is still not clear. In this study, the possible role of MCP-1, TGF-B and NF-kB in the hypertensive myocardial fibrosis and relationship between them were investigated in order to clarify the effects of MCP-1 on hypertensive myocardial fibrosis for finding the theorical basis and method totreat hypertensive myocardial fibrosis.Methods Hypertensive myocardial fibrosis model was established by administration of Nw-nitro-L-arginine methyl ester(L-NAME). Sprague-Dawley(SD) rat cardiac fibroblasts(CFs) were cultured and mononuclear cells in the blood were isolated. MCP-1 mRNA and TGF-P mRNA levels were detected by reversed transcription-polymerase chain reaction(RT-PCR). MCP-1 protein levels were determined by western blot and enzyme-linked immunoadsordent assay(ELISA). Collagen concentration were measured by determining the hydroxyproline concentration. The amount of cells was determined by MTT. The fibrosis in the myocardium was valued by image analyzing.Results (1) Chronic inhibition of nitric oxide synthesis increased arterial pressure compared with control group, but the arterial pressure of L-NAME+Captoril group has no significant difference compared with control group on every time point. (2) Chronic inhibition of nitric oxide synthesis caused significant interstitial fibrosis and perivescular fibrosis. Collagen volume fraction(CVF) of 7-day group, 14-day group and 28-day group was 4.45% +0.20%, 5.42% +0.68% and 7.02% +0.82% respectively, which was significantly different compared with the control group(3.12% + 0.08%)(P<0.05). CVF of L-NAME+Captoril group was 3.14% +0.11%, which was no significantly different compared with the control group(3.12% + 0.08%)(P>0.05). Perivascular collagen area(PVCA) was 0.85% + 0.09%, 1.18% + 0.16% and 1.52% + 0.20% respectively, which was significantly different compared with the control group(0.51% + 0.05%)(P<0.05). PVCA of L-NAME+Captoril group was 0.53% +0.07%, which was significantly different compared with the control group (0.51%+ 0.05%)(P>0.05).(3) Marked increased expression of MCP-1 mRNA was observed in the heart tissue on the 3rd day of treatment and declined with the further L-NAME administration. The level of MCP-1 mRNA of 3-day group, 7-day group, 14-day group and 28-day group was 0.82 +0.12, 0.38 +0.06, 0.31 +0.05 and 0.22 +0.02 respectively, which was significantly differentcompared with the control group(0.11 +0.01)(P<0.05). MCP-1 mRNA level of L-NAME+Captoril group was 0.12 + 0.02, which was no significantly different compared with the control group(P>0.05). (4) Expression of TGF-p mRNA was increased during chronic inhibition of nitric oxide synthesis and sustained at the high level until the 28th day. The level of TGF-p mRNA was 1.13 + 0.08, 1.52 + 0.17 and 1.46 + 0.12 respectively, which was significantly different with the control group(0.18 + 0.02)(P<0.05). There was no significant difference between the 3-day group(0.21 +0.03) and the control group(0.18 + 0.02)(P>0.05). The level of TGF-p mRNA of L-NAME+Captoril group was 0.20 + 0.03, which was no significantly different with the control group(0...
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