白藜芦醇影响一氧化氮途径对大鼠急性酒精性肝损伤的保护作用

Protective Effects of Resveratrol on Alcohol-induced Hepatic Injury through Nitric Oxide Pathway in Rats

关键词:  白藜芦醇  酒精性肝损伤  氧化应激  炎性因子  一氧化氮  诱导型一氧化氮合成酶

Key words:  resveratrol  alcoholic hepatic injury  oxidative stress  inflammatory cytokines  NO  iNOS

摘要:

目的 研究白藜芦醇(resveratrol，Res)对酒精性肝损伤后肝组织氧化反应和炎性反应的影响及与一氧化氮(NO)、诱导型一氧化氮合成酶(iNOS)通路的关系。方法 大鼠灌胃给予55度红星二锅头复制肝损伤模型。大鼠随机分为正常对照组、肝损伤模型对照组、Res低剂量组(25 mg·kg^-1)、Res中剂量组(50 mg·kg^-1)、Res高剂量组(100 mg·kg^-1 )，每日2次，连续7 d。采用试剂盒测定肝脏组织乳酸脱氢酶(LDH)、活性氧(ROS)、还原型谷胱甘肽(GSH)、NO、iNOS和血清IL-10、IFN-γ水平。Western blot测定iNOS表达，RT-PCR测定iNOS mRNA表达。结果 与正常对照组相比，酒精性肝损伤模型组肝组织LDH、ROS、NO浓度显著升高(P<0.01)、GSH显著下降(P<0.01)，血清IFN-γ水平显著升高、IL-10显著降低(P<0.01)，肝组织iNOS和iNOS mRNA表达增加(P<0.01)。与模型组相比，Res显著降低肝脏组织ROS、LDH、NO浓度(P<0.01)，降低血清IFN-γ水平和升高血清IL-10与肝脏组织GSH含量(P<0.01)，减少iNOS和iNOS mRNA表达(P<0.01)。结论 Res可能通过NO通路，消除氧化性应激状态，改变炎性因子水平，对酒精性肝损伤发挥防治作用。

Abstract:

OBJCETIVE To investigate the effects of resveratrol (Res) on alcohol-induced hepatic injury and the relationship with nitric oxide (NO) pathway. METHODS The rats were randomly divided into 5 groups, including the normal control group, alcohol-induced hapatic injuried model group, Res 25 mg·kg^-1 group, Res 50 mg·kg^-1 group and Res 100 mg·kg^-1 group. The hepatic injuried model was imitated by ig 55°Red Star Erguotou. Res was administrated twice daily, continuously for 7 days. The contents of lactate dehydrogenase (LDH), reactive oxygen species (ROS), reduced glutathione (GSH), nitric oxide (NO), induced nitric oxide synthase (iNOS) in liver and the concentrations of serum IFN-γ, IL-10 were determined by the commercial kits. The expression of iNOS was determined by Western blot and the level of iNOS mRNA was measured by real-time RT-PCR. RESULTS Compared with the normal control group, the concentrations of LDH, ROS, NO in liver were significantly increased (P<0.01) and GSH was significantly reduced (P<0.01) in the model group. Meantime, in the model group, the level of serum IFN-γ was significantly augmented and serum IL-10 depressed (P<0.01). In addition, the expressions of iNOS and iNOS mRNA were significantly increased (P<0.01). Res reduced the levels of LDH, ROS, NO and iNOS in liver and IFN-γ in serum compared with the model group, respectively. Furthermore, Res significantly increased the concentrations of serum IL-10 and hepatic GSH. Additionally, Res significantly suppressed the expressions of iNOS and iNOS mRNA in liver. CONCLUSION Res may prevent liver from alcoholic impairment via NO pathway.