Abstract:
AIM:To evaluate the effects of diazoxide on ischemia/reperfusion (I/R)-injured hepatocytes and further elucidate its underlying mechanisms. METHODS:Male Sprague-Dawley rats were randomized (8 for donor and recipient per group) into five groups: I/R group (4 h of liver cold ischemia followed by 6 h of reperfusion); heme oxygenase-1 (HO-1) small interfering RNA (siRNA) group (injection of siRNA via donor portal vein 48 h prior to harvest); diazoxide (DZ) group (injection of DZ via donor portal vein 10 min prior to harvest); HO-1 siRNA + DZ group; and siRNA control group. Blood and liver samples were collected at 6 h after reperfusion. The mRNA expressions and protein levels of HO-1 were determined by reverse transcription polymerase chain reaction and Western blotting, and tissue morphology was examined by light and transmission electron microscopy. Serum transaminases level and cytokines concentration were also measured. RESULTS:We observed that a significant reduction of HO-1 mRNA and protein levels in HO-1 siRNA and HO-1 siRNA + DZ group when compared with I/R group, while the increases were prominent in the DZ group. Light and transmission electron microscopy indicated severe disruption of tissue with lobular distortion and mitochondrial cristae damage in the HO-1 siRNA and HO-1 siRNA + DZ groups compared with DZ group. Serum alanine aminotransferase, aspartate transaminase, tumor necrosis factor-α and interleukin-6 levels increased in the HO-1 siRNA and HO-1 siRNA + DZ groups, and decreased in the DZ group. CONCLUSION:The protective effect of DZ may be induced by upregulation of HO-1. By inhibiting expression of HO-1, this protection pretreated with DZ was abolished.
journal_name
World J Gastroenteroljournal_title
World journal of gastroenterologyauthors
Zeng Z,Huang HF,He F,Wu LX,Lin J,Chen MQdoi
10.3748/wjg.v18.i15.1765subject
Has Abstractpub_date
2012-04-21 00:00:00pages
1765-72issue
15eissn
1007-9327issn
2219-2840journal_volume
18pub_type
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journal_title:World journal of gastroenterology
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pub_type: 杂志文章,meta分析,评审
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pub_type: 杂志文章
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更新日期:2012-05-07 00:00:00
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pub_type: 杂志文章,评审
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pub_type: 杂志文章
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journal_title:World journal of gastroenterology
pub_type: 杂志文章
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