Gender differences in hepatic ischemic reperfusion injury in rats are associated with endothelial cell nitric oxide synthase-derived nitric oxide

• Published in: World journal of gastroenterology : WJG Vol. 11; no. 22; pp. 3441 - 3445
• Main Authors: Lü, Ping, Liu, Fang, Wang, Chun-You, Chen, Dao-Da, Yao, Zhong, Tian, Yuan, Zhang, Jing-Hui, Wu, Yi-Hua
• Format: Journal Article
• Language: English
• Published: United States Department of GeneralSurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China%Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China%Cold Spring Harbor Laboratory, New York 11724, USA%General Surgery Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China 14.06.2005; Baishideng Publishing Group Inc
• Subjects: Animals; Basic Research; Endothelial Cells - enzymology; Female; Liver - cytology; Liver - metabolism; Male; Nitric Oxide - metabolism; Nitric Oxide Synthase - metabolism; Nitric Oxide Synthase Type III; Rats; Rats, Wistar; Reperfusion Injury - metabolism; Sex Characteristics; 一氧化氮合酶; 缺氧再灌注损伤; 肝脏损伤; Endothelial constitutive nitric oxide synthase; Gender identity; Liver; Reperfusion injury
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v11.i22.3441

AIM: This study was designed to examine the hypothesis that gender differences in I/R injury are associated with endothelial cell nitric oxide synthase (eNOS)-derived nitric oxide (NO).METHODS: Wistar rats were randomized into sevenexperimental groups (12 animals per group). Except for the sham operated groups, all rats were subjected to total liver ischemia for 40 rain followed by reperfusion. All experimental groups received different treatments 45 rain before the laparotomy. For each group, half of the animals(six) were used to investigate the survival; blood samples and liver tissues were obtained in the remaining six animals after 3 h of reperfusion to assess serum NO, alanin eaminotransferase (ALl) and TNF-α levels, liver tissue malondialdehyde (MDA) content, and severity of hepatic I/R injury.RESULTS: Basal serum NO levels in female shamoperated (FS) group were nearly 1.5-fold of male sham operated (MS) group (66.7±11.0 μmol/1 vs 45.3+10.1 μmol/L, P<0.01). Although serum NO levels decreased significantly after hepatic I/R (P<0.01, vs sham operated groups), they were still significantly higher in female rat (F) group than in male rat (M) group (47.8±8.6 μmol/1 vs23.8+4.7 μmol/L, P<0.01). Serum ALl and TNF-α levels,and liver tissue MDA content were significantly lower in F group than in M group (370.5±46.4 U/L, 0.99±0.11 μg/L and 0.57±0.10 μmol/g vs668.7±78.7 U/L, 1.71±0.18 μg/L and 0.86+0.11 μmol/g, respectively, P<0.01). I/R induced significant injury to the liver both in M and F groups (P<0.01 vs sham operated groups). But the degree of hepatocyte injury was significantly milder in F group than in M group (P<0.05 and P<0.01). The median survival time was six days in F group and one day in M group. The overall survival rate was significantly higher in F group than in M group (P<0.05). When compared with male rats pretreated with saline (M group), pretreatment of male rats with 17-β-estradiol (E2) (M+E2 group) significantly increased serum NO levels and significantly decreased serum ALT and TNF-α levels, and liver tissue MDA content after I/R (P<0.01).The degree of hepatocyte injury was significantly decreased and the overall survival rate was significantly improved in M+E2 group than in M group (P<0.01 and P<0.05). The NOS inhibitor N^W-nitro-L-arginine methyl ester (L-NAME) treatment could completely abolish the protective effects of estrogen in both male and female rats.CONCLUSION: The protective effects afforded to female rats subjected to hepatic I/R are associated with eNOS-derived NO.