| The incidence rate and case fatality of the pulmonary fibrosis increase year by year high, the pathogenesy hasn't yet been completely clear. Alveolar macrophage (AM) acts important effect in the pathogenesy of pulmonary fibrosis. The increasing of the foam cell converting from has been conformed by previous research, but it's action in pulmonary fibrosis pathogenesy still not clear. The transforming growth factorβ1(TGF-β1) is the most important cytokine in the research of pulmonary fibrosis, and is considered to be the most intensive accelerant in the deposition of extracellular matrix that discovers up to the present. the content of TGF-β1 increases in various factors cause of the pulmonary fibrosis(ep. Bleomycin, endoxand and radioactive ray). The connective tissue growth factor (CTGF) is a kind of to secreted polypeptide enriching aminothiopropionic acid, and acts as a downstream preparator of TGF-β1 to mediate TGF-β1 resulting in fibrosis. CTGF turn to have the importance contact with fibrosis in skin, liver, kidney etc, but in the function of pulmonary fibrosis study not much. It's been thought of high in the relation of the nitrogen (NO) to the pulmonary fibrosis. Aminoguanidine, a inhibitor of the inducible nitric oxide synthase (iNOS), can degrade the activityof iNOS in the lung homogenate significant, reduce NO to release, lessen alveolar catarrh. As NO inside the lung increasing, the quantity of iNOS immunoactive cells is multiplication, the ability of releases NO enhance in AM. Rosiglitazone (RSG) is the particularity ligand of the peroxisome proliferator-activated receptorγ(PPARγ). The PPARγis a nuclear receptor that can regulate the gene of lipoid metabolism and glycometabolism. It still has a controversy of the function in the foam cell formation.We induce the rat pulmonary fibrosis with the bleomycin A5 (BLM A5), and carry on an intervention by RSG, observe the change of proportional of alveolar foam cell (AF), and compare with the change of TGF-β1, CTGF and the iNOS expression between AM and AF, study the function of AF in the pathogenesy of pulmonary fibrosis, and the influence of RSG.1 The variation of proportion AF and the influence of rosiglitazoneAim To approach the influence of the treatment amount of RSG in proportion of AF of the pulmonary fibrosis.Methods 60 healthy male SD rat divide for two major groups: 14 days group and 28 days group14 days group contains 4 groups, (n=6). Sham 14th group (Sham14), RSG 14th group (R14), BLM+NS 14th group (B+NS14), BLM+RSG 14th group (B+R14).28 days group is divided into 6 groups, (n=6): Sham 28th group (Sham28), RSG 28th group (R28), BLM+NS 28th group (B+NS28), BLM+RSG 28th group (B+R28), BLM+RSG fore 14th+NS last 14th group (B+R14NS14), BLM+NS fore 14th+RSG last 14th group (B+NS14R14).We carry on bronchoalveolar lavage to observate total amount of cell in bronchoalveolar lavage fluid (BALF), utilize oil red O staining to estimate the proportion of the foam cell in the BALF.ResultsCounting of cells in BALF: Each RSG group compares to Sham group, the cell quantity to shows no obvious difference (P>0.05). After inject BLM in the windpipe, the cell total amount increment in the BALF. The 14th day of the drop of BLM in the pulmonary fibrosis, the cell total amount is more than that of 28th day of the drop of BLM in the pulmonary fibrosis obviously (P<0.01). After give the RSG treatment, the cell total amount in the BALF of each treatment group is lower than their model group obviously (P<0.01), except B+NS14R14 group (no obvious difference).Percentage of oil red O active cells (namely the foam cell): Each RSG group, model group and the treatment group compares to sham group, the percentage of foam cell increases significant (P<0.01). Each treatment group compares to the model group, the percentage of foam cell increases significant (P<0.01). B+NS14R14 group compares to B+R28group and B+R14NS14 group, the percentage of foam cell decreases significance (P<0.01). B+R28 group compares to and B+R14NS14 group, the percentage of foam cell shows no obvious difference (P>0.05). B+NS28 group compares to B+NS14 group, the percentage of foam cell shows decreased significant (P<0.01). B+R28 group, B+R14NS14 group compare to B+R14 group, the percentage of foam cell shows no obvious difference (P>0.05).Conclusions In the formation of pulmonary fibrosis induced by BLM, the cell total amount of BALF increases, the proportion of foam cell promotes. The RSG partly represses the increase of BALF cell total amount that the BLM cause to, augments the proportion of the foam cell in BALF, and its function is more predominance in the first 14 days.2 The difference expression of TGF-β1, CTGF and iNOS between AM and AF, and the influence of RSGAim Through the observation of the change of expression of TGF-β1, CTGF and iNOS in AF, we try to elaborate the RSG and the foam cell the function of in pulmonary fibrosis.Methods The group is same to part oneUtilizing oil red O and immunohistochemistry double stain differentiate the expression difference of TGF-β1, CTGF and iNOS in AM and AF.ResultsImmunohistochemistry of TGF-β1 in AM and AFThe quantity and proportion of the TGF-β1 immunoactive cells in the first 14 days exceed that of the last 14 days. In the BALF, the expression of TGF-β1 in AF is more intensive than that of AM. The RSG facilitate AM converting to AF, result in the proportion of TGF-β1 cell increases, but as RSG partly represses the increase of BALF cell total amount that the BLM cause to, it make the quantity of TGF-β1 immunoactive cells reduce or have no obvious variety.Immunohistochemistry of CTGF in AM and AFThe proportion of CTGF immunoactive cells in the first 14 days exceeds that of the last 14 days, and the quantity is contrary. In the BALF, the expression of CTGF in AF is less intensive than that of AM. The RSG facilitate AM converting to AF and partly represses the increase of BALF cell total amount that the BLM cause to, result in the proportion and quantity of CTGF cell decreases, its function is more predominance in the first 14 days.Immunohistochemistry of CTGF in AM and AFThe proportion of CTGF immunoactive cells in the first 14 days exceeds that of the last 14 days, and the quantity is contrary. In the BALF, the expression of CTGF in AF is less intensive than that of AM. The RSG facilitate AM converting to AF and partly represses the increase of BALF cell total amount that the BLM cause to, result in the proportion and quantity of CTGF cell decreases, its function is more predominance in the first 14 days.Conclusions The injection of BLM at one time inside the windpipe can cause the cell TGF-β1, CTGF and iNOS expression adjusts up in the BALF. AF expression iNOS, CTGF proportion is weaker than AM. As a result the increase of foam cell sourcing macrophage may relieve the degree of lung fibrosis. The RSG partly represses the increase of expression of CTGF and iNOS that the BLM cause to, through promotes the quantity and proportion of AF in the BALF. Moreover, RSG partly represses the increase of the total amount of the BALF, so it partly represses the increment of total amount of the expression of TGF-β1, CTGF and iNOS. So we can believe RSG bring into play anti-fibrosis function through the mechanism above. |
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