Splenectomy ameliorates acute multiple organ damage induced by liver warm ischemia reperfusion in rats.
BACKGROUND
Liver ischemia/reperfusion (I/R) results in the release of destructive proinflammatory cytokines and oxygen-derived radicals, which in turn cause injury to liver and other organs such as kidney, lung, and intestine. Splenectomy protects organs from intestinal I/R injury. Therefore, the present study aims to investigate whether splenectomy could also ameliorate multiple organ damage caused by liver I/R.


METHODS
Wistar rats randomly assigned into 4 groups underwent sham-operation, splenectomy, hepatic I/R induced by occlusion of hepatic artery and portal vein, and splenectomy plus hepatic I/R, respectively. Blood samples were collected for assessing aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activity, and tumor necrosis factor-alpha (TNF-alpha) levels. The activity of myeloperoxidase (MPO) in liver tissues was assessed. Livers, kidneys, lungs, and small intestines underwent histopathologic examination for scoring injury severity and TUNEL assay for cell apoptosis. The expression of caspase-3 was evaluated with Western blot analysis.


RESULTS
Liver I/R resulted in liver injury as evidenced by morphologic abnormalities, increased serum activities of AST and ALT, and increased percentage of apoptotic cells. The activity of MPO in liver tissues and the serum levels of TNF-alpha were increased after I/R. Splenectomy significantly decreased the histologic severity score, apoptotic index, MPO activity, and serum levels of AST, ALT, and TNF-alpha. Hepatic I/R also caused damage to kidneys, lungs, and small intestines, as evaluated by histologic alterations and increased apoptotic cells; these changes were ameliorated by splenectomy. The expression of caspase-3 was upregulated in the 4 organs by hepatic I/R and inhibited by splenectomy.


CONCLUSIONS
Splenectomy protects the liver as well as the kidney, lung, and intestine from injury by hepatic I/R. Although the mechanism needs further investigation, this study demonstrated that splenectomy inhibited leukocyte infiltration in livers, release of TNF-alpha, cell apoptosis, and expression of caspase-3.
Jiang
Hongchi
H
Hepatosplenic Surgery Center/Department of General Surgery, the First Clinical College, Harbin Medical University, Peking University, Beijing, China.
Meng
Fanqiang
F
Li
Wei
W
Tong
Liquan
L
Qiao
Haiquan
H
Sun
Xueying
X
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis; D001219:Aspartate Aminotransferases / Q000097:blood; D053148:Caspase 3 / Q000378:metabolism; D007422:Intestines / Q000201:enzymology / Q000473:pathology; D007668:Kidney / Q000201:enzymology / Q000473:pathology; D008099:Liver / Q000098:blood supply* / Q000293:injuries* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009102:Multiple Organ Failure / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D013156:Splenectomy; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C505410:Casp3 protein, rat; D053148:Caspase 3