| 石洪林,余文胜.花姜酮对急性肝损伤大鼠Nrf2/HO-1/ NQO-1氧化应激损伤的影响[J].浙江中西医结合杂志,2022,32(3): |
| 花姜酮对急性肝损伤大鼠Nrf2/HO-1/ NQO-1氧化应激损伤的影响 |
| Zingerone Protects Acute Liver Injury Rats from Oxidative Stress Damage by Regulating the Nrf2/HO-1/ NQO-1 Signal Pathway |
| 投稿时间：2021-08-24 修订日期：2021-12-31 |
| DOI： |
| 中文关键词: 花姜酮 急性肝损伤 Nrf2/HO-1/ NQO-1 氧化应激 大鼠 |
| 英文关键词:Zingerone Acute liver injury Nrf2/HO-1/ NQO-1 Oxidative stress Rat |
| 基金项目: |
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| 摘要点击次数: 765 |
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| 中文摘要: |
| 目的：花姜酮对四氯化碳诱导的急性肝损伤大鼠肝脏氧化应激损伤的影响。方法：随机将大鼠分为：空白组、模型组、联苯双酯组(3.75 mg/kg)、花姜酮低剂量组(5 mg/kg)、花姜酮高剂量组(10 mg/kg),每组10只。腹腔注射给药,每日1次,每次注射0.8 mL相对应药物,连续注射5 d。空白组、模型组注射等体积生理盐水。末次注射给药2 h后,模型组、联苯双酯组、花姜酮低、高剂量组腹腔注射0.2%四氯化碳花生油溶液(0.01 mL/g),空白组予等体积花生油腹腔注射。注射四氯化碳花生油溶液后16 h戊巴比妥钠麻醉大鼠,腹主动脉取血,分离血清,ELISA法检测大鼠肝功能指标谷草转氨酶(AST)、谷丙转氨酶(ALT)活性；切取部分肝脏组织,ELISA法检测大鼠肝脏中氧化指标锰-超氧化物歧化酶(Mn-SOD)、过氧化氢酶(CAT)、活性和丙二醛(MDA)、羟自由基(.OH)、活性氧( ROS)含量；ELISA法检测肝脏组织中线粒体呼吸链复合物I、III(Complex I、III)活性；蛋白免疫印迹法检测肝组织中核因子E2相关因子2(Nrf-2),醌氧化还原酶-1(NQO-1),血红素加氧酶1(HO-1)的蛋白表达水平。结果：与模型组相比,花姜酮组大鼠血清AST(15.87±2.27、26.06±3.81)U.mL-1、ALT(15.85±1.83、24.52±2.62)U.mL-1含量降低(P<0.05)；肝组织中Mn-SOD(28.02±2.16、22.26±1.81)μg.mL-1、CAT(247.63±20.82、203.35±19.43)μg.mL-1、Complex I(103.49±8.52、91.38±7.43)、Complex III(56.24±1.65、44.72±1.71)的活性及ATP(37.67±2.72、28.13±2.48)含量较模型组高, MDA(10.18±2.15、13.26±1.64)μg.mL-1、.OH (4.13±1.52 、5.39±1.44)μg.mL-1、ROS(0.41±0.13、0.62±0.15)μg.mL-1的含量较模型组低(P<0.05)；肝组织中HO-1(0.72±0.13 、0.56±0.12)、NQO-1(0.29±0.06、0.24±0.04)、Nrf-2(0.57±0.07、0.31±0.03)蛋白表达增加(P<0.05)。结论: 花姜酮对急性肝损伤大鼠肝脏氧化应激损伤能起到保护作用,其作用机制可能与提高抗氧化因子活性,减少肝脏中ROS、.OH堆积,调节Nrf2/HO-1/ NQO-1信号通路,进而改善肝组织氧化应激状态有关。 |
| 英文摘要: |
| Objective: To investigate the effects of zingerone on liver oxidative stress damage of acute liver injury rats induced by carbon tetrachloride. Methods: Rats were randomly divided into following groups: normal control group, model control group, biphenyl diester group (3.75 mg/kg), low and high doses of zingerone groups (5 mg/kg and 10 mg/kg), with 10 animals per group. The rats were intraperitoneally injected with 0.8 ml drugs once daily for 5 days. The normal and model control groups were intraperitoneally injected with same volume of saline. Two hours after last injection, rats in model control, biphenyl diester, low and high doses of zingerone groups were intraperitoneally injected with 0.2% carbon tetrachloride peanut oil solution (0.01 ml/g). In the same time, rats in normal control group were intraperitoneally injected with same volume of peanut oil solution. Sixteen hours later, rats were anesthetized with sodium pentobarbital. The serum sample was collected from abdominal aorta blood after being centrifugated. The activities of liver function indicators aminotransferase (AST), alanine aminotransferase (ALT) were measured by ELISA kits. The activities of Manganese-superoxide dismutase (Mn-SOD), catalase (CAT) and contents of active and malondialdehyde (MDA), hydroxyl radical (?OH), reactive oxygen species (ROS) in liver tissues were analyzed by ELISA, as well as the activities of mitochondrial respiratory chain complex I and III (Complex I, III). The expressions of Nuclear factor E2-related factor 2 (Nrf-2), quinone oxidoreductase-1 (NQO-1) and heme oxygenase 1 (HO-1) protein were detected by western blot. Results: Compared with model control group, the serum levels of AST (15.87±2.27, 26.06±3.81) U.mL-1 and ALT (15.85±1.83, 24.52±2.62) U.mL-1 were significantly decreased in zingerone groups (P<0.05). The activities of Mn-SOD (28.02±2.16, 22.26±1.81) μg.mL-1, CAT (247.63±20.82, 203.35±19.43) μg.mL-1, Complex I (103.49±8.52, 91.38±7.43), Complex III (56.24±1.65, 44.72±1.71) and ATP(37.67±2.72, 28.13±2.48)content were higher than that in model control group. The contents of MDA (10.18±2.15, 13.26±1.64) μg.mL-1, .OH (4.13±1.52, 5.39±1.44) μg.mL-1 and ROS(0.41±0.13, 0.62±0.15)μg.mL-1 were decreased (P<0.05). The protein levels of HO-1 (0.72±0.13, 0.56±0.12), NQO-1 (0.29±0.06, 0.24±0.04) and Nrf-2 (0.57±0.07, 0.31±0.03) were increased (P<0.05). Conclusion: Zingerone exerts protective effect on liver oxidative stress in acute liver injury rats. The underlying mechanism may be associated with reducing the accumulation of ROS and .OH, modulating the Nrf2/HO-1/ NQO-1 signal pathway and improving the oxidative stress state of liver tissue. |
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