Influence of dexamethasone on inflammatory mediators and NF-kappaB expression in multiple organs of rats with severe acute pancreatitis.
OBJECTIVE
To observe the therapeutic effects of dexamethasone on rats with severe acute pancreatitis (SAP) and investigate the influences of dexamethasone on the inflammatory mediators and NF-kappaB expression in multiple organs of SAP rats as well as the mechanisms involved.


METHODS
Ninety Sprague-Dawley (SD) rats with SAP were randomly divided into the model group (n = 45) and dexamethasone treatment group (n = 45), and another 45 rats were selected for the sham operation group. All groups were randomly subdivided into the 3 h, 6 h and 12 h groups, each group containing 15 rats. The survival of all groups and pathological changes of multiple organs (liver, kidney and lung) were observed at different time points after the operation. The pathological score of multiple organs was carried out, followed by the determination of amylase, endotoxin and TNF-alpha contents in blood. The tissue microarray was used to detect the expression levels of NF-kappaB p65 protein in multiple organs.


RESULTS
There was no marked difference between the model group and treatment group in the survival rate. The amylase content of the treatment group was significantly lower compared to the model group at 12 h (P < 0.01, 7791.00 vs 9195.00). Moreover, the endotoxin and TNF-alpha levels of the treatment group were significantly lower than that of the model group at 6 h and 12 h (P < 0.01, 0.040 vs 0.055, 0.042 vs 0.059 and P < 0.05, 58.30 vs 77.54, 38.70 vs 67.30, respectively). Regarding the changes in liver NF-kappaB expression, the model group significantly exceeded the sham operation group at 3 h (P < 0.01, 1.00 vs 0.00), and the treatment group significantly exceeded the sham operation group at 12 h (P < 0.01, 1.00 vs 0.00), whereas no marked difference was observed between the model group and treatment group at all time points. The kidney NF-kappaB expression level in the treatment group significantly exceeded the model group (P < 0.05, 2.00 vs 0.00) and the sham operation group (P < 0.01, 2.00 vs 0.00) at 12 h. No NF-kappaB expression in the lung was found in any group.


CONCLUSIONS
Dexamethasone can lower the amylase, endotoxin and TNF-alpha levels as well as mortality of SAP rats. NF-kappaB plays an important role in multiple organ injury. Further studies should be conducted to determine whether dexamethasone can ameliorate the pathological changes of multiple organs by reducing the NF-kappaB expression in the liver and kidney. The advantages of tissue microarrays in pancreatitis pathological examination include time- and energy- saving, and are highly efficient and representative. The restriction of tissue microarrays on the representation of tissues to various extents due to small diameter may lead to the deviation of analysis.
Zhang
Xi-Ping
XP
Department of General Surgery, Hangzhou First People's Hospital, 261 Huansha Road, Hangzhou 310006, Zhejiang Province, China. zxp99688@vip.163.com
Zhang
Ling
L
Chen
Lin-Jie
LJ
Cheng
Qi-Hui
QH
Wang
Jian-Mei
JM
Cai
Wei
W
Shen
Hai-Ping
HP
Cai
Jun
J
D000208:Acute Disease; D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000032:analysis*; D007668:Kidney / Q000737:chemistry / Q000473:pathology; D008099:Liver / Q000737:chemistry / Q000473:pathology; D008168:Lung / Q000737:chemistry / Q000473:pathology; D016328:NF-kappa B / Q000032:analysis*; D010195:Pancreatitis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015996:Survival Rate; D046888:Tissue Array Analysis; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D018836:Inflammation Mediators; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone