MG132 Alleviates Liver Injury Induced by Intestinal Ischemia/Reperfusion in Rats: Involvement of the AhR and NF魏B Pathways

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• 作者：Huirong Jing ; M.D.^&lowast ; ; Gang Shen ; M.D.^&lowast ; ; Guangzhi Wang ; M.D.^&lowast ; ; Feng Zhang ; M.D.^&lowast ; ; Yubing Li ; M.D.^&dagger ; ; Fuwen Luo ; M.D. ; Ph.D.^&lowast ; ; Jihong Yao ; M.D. ; Ph.D.^&dagger ; ; ^{Yaojihong65@hotmail.com} ; Xiao-Feng Tian ; M.D. ; Ph.D.^&lowast ; ; ^{txfdl@hotmail.com}
• 关键词：AhR ; MG132 ; liver injury ; intestinal ischemia/reperfusion ; cyp1a2 ; I魏B伪 ; NF魏Bp65
• 刊名：Journal of Surgical Research
• 出版年：2012
• 期刊代码：299_00224804
• 类别：med
• 出版时间：July, 2012
• 卷：176
• 期：1
• 页码：63-73
• 文件大小：2598 K

摘要

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Background

MG132 is a potent antioxidant and has been reported to play a protective role in ischemia/reperfusion (I/R) of many organs. Recent studies have shown that the Aryl hydrocarbon receptor (AhR) may play a beneficial role in I/R of many organs and an AhR agonist has been implicated in an anti-inflammatory role. MG132 might function as an AhR agonist through proteasome inhibition, possibly through the inhibition of NF魏B. Herein, we hypothesized that MG132 may play a protective role in liver injury induced by intestinal I/R and we analyzed the expression behavior of AhR and NF魏B to determine whether the two factors play a role in intestinal I/R.

Materials and Methods

Thirty-two Sprague-Dawley rats were divided into four groups: control, I/R, MG132 control, and MG132 pretreatment. The I/R and MG132 pretreatment groups were subjected to mesenteric arterial ischemia for 1 h and reperfusion for 3 h. The control and MG132 control groups underwent surgical preparation including isolation of the superior mesenteric artery (SMA) without occlusion. The MG132 control and MG132 pretreatment groups were subjected to intraperitoneal administration of 0.5 mg/kg MG132 30 min before surgery. We collected serum specimens to measure TNF-伪, IL-6, liver tissue levels of malondialdehyde (MDA), AhR, and cyp1a2; NF魏B, I魏B伪, and ICAM-1 were also tested. Histologic changes of liver and intestine were subsequently evaluated.

Results

Compared with the control group, significant increases in MDA, NF魏B, and ICAM-1 levels were accompanied by decreases in AhR, cyp1a2, and I魏B伪 expression in the liver in the I/R group, which is consistent with liver and intestinal tissue injury. MG132 blocked the alterations of the indicators above. There were no changes in the MG132 control group compared with the control group in the indicators above.

Conclusions

This study demonstrated that MG132 has a significant effect in protection against liver injury induced by intestinal I/R, which may be due to modulation of the AhR and NF魏B pathways.