[Early expression of pro-inflammatory cytokines in the lung of rat with small-for-size liver transplantation and the significance].
OBJECTIVE
To investigate the expression of tumor necrosis factor-alpha(TNF-alpha), interleukin-1 beta (IL-1beta), and intercellular adhesion molecule-1 (ICAM-1) in the lung of rat with small-for-size liver transplantation and the significance of the expression of these cytokine in lung injury after liver transplantation.


METHODS
150 SD rats were randomly divided into 4 groups: sham operation group (n = 6), whole graft liver transplantation group (n = 48), 50% size graft liver transplantation group (n = 48), and 30% size liver transplantation group (n = 48). Six rats from each group were killed 0.5, 2, 6, and 24 hours after operation. Blood samples from subhepatic inferior vena cava were obtained to examine the plasma TNF-alpha by ELISA. Specimens of lung were obtained to be examined pathologically. RT-PCR was used to examine the expression of TNF-alpha mRNA, IL-1beta mRNA, and ICAM-1 mRNA in lung, and chromatometry was performed to detect the activity of myeloperoxidase (MPO).


RESULTS
(1) The plasma TNF-alpha at any time point was higher in the 3 transplantation groups than in the sham operation group. The plasma TNF-alpha 2 hours after operation in the whole graft group was significantly higher than that in the 30% size group (P < 0.05). (2) The expression levels of TNF-alpha mRNA 2 and 6 hours after operation in the whole graft group and in the 50% graft group were significantly higher than those in the 30% graft group (all P < 0.01). The expression levels of TNF-alpha mRNA remained significantly higher than those in the sham operation group since the second hour after operation (all P < 0.01). (3) IL-1beta mRNA was expressed in the 3 liver transplantation groups without significant differences between any levels at all the time points and was not expressed in the sham operation group. The expression of ICAM-1 mRNA was higher at all the time points in the liver transplantation groups than in the sham operation group (P < 0.01 or P < 0.05) without significant difference between the values of any transplantation group at any time point (all P > 0.05). The MPO activity was stronger in the 3 liver transplantation groups at any time point than in the sham operation group (all P < 0.01). The peak occurred 2 hours after operation in the whole graft group and 50% size group and occurred 6 hours after operation in the 30% graft group. The plasma TNF-alpha level was positively correlated to the MPO activity in lung tissue with a correlation coefficient of 0.422 (P < 0.05). (4) The morphology of lung was normal in the sham operation group. Obvious interstitial hyperemia and hemorrhage, neutrophil infiltration, and pulmonary septal thickening were found in the 3 transplantation groups, in particular being severe at the 2-hour time point.


CONCLUSIONS
Increase of plasma TNF-alpha is one of the causes of lung injury after small-for-size liver transplantation. Upregulation of TNF-alpha mRNA, IL-1beta mRNA, and ICAM-1 mRNA expression may be also responsible for the lung injury and their expression may be correlated to the size of graft.
Zheng
Shu-sen
SS
Department of Hepatobiliary and Pancreas Surgery, First Affiliated Hospital of Medical College, Zhejiang University, Hangzhou 310003, China.
Xu
Shi-guo
SG
Liang
Ting-bo
TB
Qin
Yun-sheng
YS
Wei
Jian-feng
JF
Jiang
Guo-ping
GP
D000818:Animals; D007375:Interleukin-1 / Q000235:genetics*; D016031:Liver Transplantation; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000235:genetics*
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase