The protective effects of 17beta-estradiol on hepatic ischemia-reperfusion injury in rat model, associated with regulation of heat-shock protein expression.
BACKGROUND
Ischemia-reperfusion (I/R) injury, which was commonly seen in the field of hepatic surgical intervention, impaired liver regeneration and predisposed to liver failure. Previous studies have shown gender dimorphic response of the liver for various hepatic stresses including I/R injury, hemorrhagic shock-resuscitation, liver cirrhosis, endotoxemia, and chronic alcoholic consumption, and demonstrated gender dimorphism in hepatocellular dysfunction after experimental trauma and hemorrhage. The objective of this study was to examine the hypothesis that the protective effects of 17beta-estradiol (E2) in hepatic I/R injury were associated with increasing heat-shock protein 70 expression.


METHODS
Sprague-Dawley male and female rats were randomly divided into male and female sham, I/R, and E2 + I/R groups. The model of reduced-size liver ischemia and reperfusion was used. Except for the sham-operated groups, all rats were subjected to 70% liver ischemia for 45 min followed by resection of the remaining 30% nonischemic lobes and reperfusion of ischemic tissue. For each group, five rats were used to investigate the survival during a week after operation; blood samples and liver tissues were obtained in the remaining animals after 3, 12, and 24 h of reperfusion to assess serum alanine aminotransferase, aspartate aminotransferase, liver tissue NO(2)(-) + NO(3)(-), malondialdehyde content, superoxide dismutase, nitric oxide synthase, and myeloperoxidase activity, Hsp70 expression, and apoptosis ratio.


RESULTS
Compared with I/R groups, male and female E2 + I/R groups showed less I/R-induced injury, and SOD and eNOS activity and Hsp70 expression were increased significantly (P < 0.01). A higher rate of apoptosis was observed in the I/R group versus the E2 + I/R group, a significant increase of MDA, NO(2)(-) + NO(3)(-), and MPO of liver tissues and serum transaminase were also observed in the I/R group versus the E2 + I/R group. The survival rate was significantly higher in the male E2 + I/R group than in the male I/R group.


CONCLUSIONS
E2 pretreatment had protective effects on liver in hepatic I/R injury. The mechanism of this protection might be related to overexpression of Hsp70.
Shen
Shi-Qiang
SQ
Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China.
Zhang
Yuan
Y
Xiong
Cheng-Long
CL
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D004195:Disease Models, Animal; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D013482:Superoxide Dismutase / Q000378:metabolism
D018840:HSP70 Heat-Shock Proteins; D009569:Nitric Oxide; D004958:Estradiol; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; D013482:Superoxide Dismutase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase