ABSTRACT
Objective To investigate the effect of the inhibitor SB203580 of p38 mitogen-activated protein kinase (MAPK) signal transduction pathway on biopterin (BH 4)/nitric oxide (NO) expression and elucidate the potential mechanism of MAPK in biopterin-mediated NO induction after endotoxic shock. Methods A total of 56 male Wistar rats were randomly divided into normal control group (n=8), endotoxic shock group (n=32) and SB203580 treatment group (n=16). After animals were sacrificed, tissue samples from the liver, the lungs as well as the kidneys were harvested to determine the expressions of guanosine triphosphate cyclohydrolase I (GTP-CHI) and inducible nitric oxide synthase (iNOS) mRNA and observe the changes of BH 4 and NO levels in blood and tissues. Results With endotoxin challenge, GTP-CHI mRNA expression and BH 4 levels were significantly elevated in various tissues and maintained at high levels up to 24 hours. Similarly, the iNOS mRNA expression and NO levels in the tissues significantly increased too, especially in the liver and the lungs. Treatment with SB203580 significantly down-regulated GTP-CHI mRNA expression in the liver, the lungs and the kidneys at 12, 24 and 2-12 hours, respectively (P
ABSTRACT
Objective To investigate the effect of nuclear factor-kappa B (NF-?B) signal transcription pathway inhibitor-pyrrolidine dithiocarbamate (PDTC) on mRNA expression of high mobility group box-1 protein (HMGB1) in organs of rats with endotoxic shock and its potential mechanism. Methods Forty-seven male Wistar rats were randomly divided into normal control group (n=8), endotoxic shock group (n=24), and PDTC treatment group (n=15). At serial time points, the animals in each group were sacrificed, and tissue samples from the liver, lungs and kidneys were harvested to determine HMGB1 mRNA expression and pulmonary MPO activity. Also, blood samples were collected to determine the major organ functional indices. Results Compared to normal controls, HMGB1 mRNA levels were significantly increased in samples from the liver, lungs and kidneys at 2-6h after endotoxin challenge (P