萝卜硫素通过 Nrf2-ARE 通路保护肠缺血再灌注引起的肝损伤。
Sulforaphane protects liver injury induced by intestinal ischemia reperfusion through Nrf2-ARE pathway.
机构信息
Department of General Surgery, Second Affiliated Hospital of Dalian Medical University, Dalian 116023, Liaoning Province, China.
出版信息
World J Gastroenterol. 2010 Jun 28;16(24):3002-10. doi: 10.3748/wjg.v16.i24.3002.
AIM
To investigate the effect of sulforaphane (SFN) on regulation of NF-E2-related factor-2 (Nrf2)-antioxidant response element (ARE) pathway in liver injury induced by intestinal ischemia/reperfusion (I/R).
METHODS
Rats were divided randomly into four experimental groups: control, SFN control, intestinal I/R and SFN pretreatment groups (n = 8 in each group). The intestinal I/R model was established by clamping the superior mesenteric artery for 1 h and 2 h reperfusion. In the SFN pretreatment group, surgery was performed as in the intestinal I/R group, with intraperitoneal administration of 3 mg/kg SFN 1 h before the operation. Intestine and liver histology was investigated. Serum levels of aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were measured. Liver tissue superoxide dismutase (SOD), myeloperoxidase (MPO), glutathione (GSH) and glutathione peroxidase (GSH-Px) activity were assayed. The liver transcription factor Nrf2 and heme oxygenase-1 (HO-1) were determined by immunohistochemical analysis and Western blotting analysis.
RESULTS
Intestinal I/R induced intestinal and liver injury, characterized by histological changes as well as a significant increase in serum AST and ALT levels (AST: 260.13 +/- 40.17 U/L vs 186.00 +/- 24.21 U/L, P < 0.01; ALT: 139.63 +/- 11.35 U/L vs 48.38 +/- 10.73 U/L, P < 0.01), all of which were reduced by pretreatment with SFN, respectively (AST: 260.13 +/- 40.17 U/L vs 216.63 +/- 22.65 U/L, P < 0.05; ALT: 139.63 +/- 11.35 U/L vs 97.63 +/- 15.56 U/L, P < 0.01). The activity of SOD in the liver tissue decreased after intestinal I/R (P < 0.01), which was enhanced by SFN pretreatment (P < 0.05). In addition, compared with the control group, SFN markedly reduced liver tissue MPO activity (P < 0.05) and elevated liver tissue GSH and GSH-Px activity (P < 0.05, P < 0.05), which was in parallel with the increased level of liver Nrf2 and HO-1 expression.
CONCLUSION
SFN pretreatment attenuates liver injury induced by intestinal I/R in rats, attributable to the antioxidant effect through Nrf2-ARE pathway.
目的
研究萝卜硫素（SFN）对肠缺血再灌注（I/R）诱导的肝损伤中核因子 E2 相关因子 2（Nrf2）-抗氧化反应元件（ARE）通路的调节作用。
方法
大鼠随机分为 4 个实验组：对照组、SFN 对照组、肠 I/R 组和 SFN 预处理组（每组 8 只）。通过夹闭肠系膜上动脉 1 小时和再灌注 2 小时来建立肠 I/R 模型。在 SFN 预处理组中，在手术前 1 小时腹腔内给予 3mg/kg SFN。观察肠和肝组织学变化。检测血清天冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT）水平。测定肝组织中超氧化物歧化酶（SOD）、髓过氧化物酶（MPO）、谷胱甘肽（GSH）和谷胱甘肽过氧化物酶（GSH-Px）的活性。用免疫组化分析和 Western blot 分析检测肝转录因子 Nrf2 和血红素加氧酶-1（HO-1）。
结果
肠 I/R 导致肠和肝损伤，其特征为组织学变化以及血清 AST 和 ALT 水平显著升高（AST：260.13±40.17 U/L 比 186.00±24.21 U/L，P<0.01；ALT：139.63±11.35 U/L 比 48.38±10.73 U/L，P<0.01），所有这些均通过 SFN 预处理降低，分别为（AST：260.13±40.17 U/L 比 216.63±22.65 U/L，P<0.05；ALT：139.63±11.35 U/L 比 97.63±15.56 U/L，P<0.01）。肝组织 SOD 活性在肠 I/R 后降低（P<0.01），SFN 预处理增强了其活性（P<0.05）。此外，与对照组相比，SFN 显著降低了肝组织 MPO 活性（P<0.05），并提高了肝组织 GSH 和 GSH-Px 活性（P<0.05，P<0.05），这与肝 Nrf2 和 HO-1 表达水平的增加相一致。
结论
SFN 预处理可减轻大鼠肠 I/R 诱导的肝损伤，归因于通过 Nrf2-ARE 通路的抗氧化作用。
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