RESUMO
Objective To investigate the expression and the effects of tissue inhibitor of metalloproteinases-1 (TIMP-1) on lungs of rats with sepsis.Methods Forty Sprague-Dawley (SD) rats were randomly divided into two groups,namely sham group (n =8) and sepsis model group (n =32).The rats of model group were modeled by cecal ligation and puncture (CLP),and were further divided into four subgroups as per the time after modeling,namely 6 h (n =8),12 h (n =8),24 h (n =8),48 h (n =8)subgroups.Blood and lung samples were taken 6 h,12 h,24 h and 48 h after modeling.The histological changes in lungs of the rats were observed under light microscope.Expressions of TIMP-1 mRNA,Bax mRNA and Bcl-2 mRNA in lungs were measured by RT-PCR.The immunohistochemistry was used to label the CD18 in lungs during different phases of sepsis.The data were processed by t test.Results Compared with sham group,the lung tissues of rats in model group were injured to a certain extent after CLP.The expression of TIMP-1 mRNA and the number of CD18 positive cells increased at the same time (P ＜ 0.01),and peaked 24 hours later (P ＜ 0.01).While the expression of Bax mRNA in model group decreased markedly 12-48 hours after modeling (P ＜ 0.01-0.05),and reached minimum 48 hours later (P ＜ 0.01).The expression of Bcl-2 mRNA in model group changed unnoticeable.The positive correlation between variations in number of CD18 positive cells and expression of TIMP-1 mRNA was found in model group (r =0.426,P ＜ 0.01).Conclusions The increase in expression of TIMP-1 mRNA in lungs is closely associated with the lung injury of sepsis.The mechanism of lung injury is likely attributed to the preservation of inflammatory cells from apoptosis,and the persistent inflammation response causes tissue damage,leading to organ dysfunction.
RESUMO
Objective To investigate the changes in the serum MMP-9 (matrix metalloproteinase-9) and the expressions of MMP-9 in lung, kidney and intestine in rats with multiple organ dysfunction syndrome (MODS) and confirm extracellular matrix injuries being the mechanism in MODS in order to propose a novel theoretical basis for cfinical treatment of MODS. Method Forty wister rats were randomly divided into two groups: control group (n=8) and MODS model group (n=32). The rats of model group were further divided into four subgroups ac-cordingto the time elapsed after modelling: 12 h (n=8), 24 h(n=8) ,48 h(n=8) and 72 h (n=8), and were modelled by celiac injection of mixed liquid of zymosan-paraffin (4 mL/100 g) after blood loss (1mL/100 g) by extirpating their left eyes. Blood,lung, kidney and intestine were sampled 12,24,48 and 72 hours after models were established. The histological changes in the lung, kidney and intestine of the rats were observed by light mi-croscope. The serum MMP-9 were measured by enzyme-linked immunosorbent assay (ELISA). The immunohisto-chemistry was used to observe the expression of MMP-9 in lung,kidney and intestine during different phases of MODS. The data were processed by one-way ANOVA and Bivariate analysis. Results Compared with control group, the organs were injured by congestion, edema and inflammatory cells infiltration to a certain extent in model groups. The serum MMP-9 increased markedly 12 hours after modelling (P<0.01 ) and peaked 48 hours later. The expressions of MMP-9 in lung, kidney and small intestine significantly increased from 12 h to 72 h after mod-elling (P<0.01 or 0.05). Conclusions The MMP-9 increased both in serum and tissue are closely associated with the pathological process of MODS. The mechanism of organ damage probably attributes to the damage of extra-celluar matrix and tissue construction.