Liu Jing-Li, Du Jun, Fan Ling-Ling, Liu Xiao-Yan, Gu Luo, Ge Ying-Bin
Department of Physiology, Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
World J Gastroenterol. 2008 May 28;14(20):3242-8. doi: 10.3748/wjg.14.3242.
To investigate the effect of quercetin (3,3',4',5,7-pentahydroxy flavone), a major flavonoid in human diet, on hyper-proliferation of gastric mucosal cells in rats treated with chronic oral ethanol.
Forty male Sprague-Dawley rats, weighing 200-250 g, were randomly divided into control group (tap water ad libitum), ethanol treatment group (6 mL/L ethanol), quercetin treatment group (intragastric gavage with 100 mg/kg of quercetin per day), and ethanol plus quercetin treatment group (quercetin and 6 mL/L ethanol). Expression levels of proliferating cell nuclear antigen (PCNA) and Cyclin D1 were detected by Western blot to assay gastric mucosal cell proliferation in rats. To demonstrate the influence of quercetin on the production of extra-cellular reactive oxygen species/nitrogen species (ROS/RNS) in rats, changes in levels of thiobarbituric acid reactive substance (TBARS), protein carbonyl, nitrite and nitrate (NOx) and nitrotyrosine (NT) were determined. The activity of inducible nitric oxide synthase (NOS) including iNOS and nNOS was also detected by Western blot.
Compared to control animals, cell proliferation in the gastric mucosa of animals subjected to ethanol treatment for 7 days was significant increased (increased to 290% for PCNA density P < 0.05, increased to 150 for Cyclin D1 density P < 0.05 and 21.6 +/- 0.8 vs 42.3 +/- 0.7 for PCNA positive cells per view field), accompanied by an increase in ROS generation (1.298 +/- 0.135 micromol vs 1.772 +/- 0.078 micromol for TBARS P < 0.05; 4.36 +/- 0.39 mmol vs 7.48 +/- 0.40 mmol for carbonyl contents P < 0.05) and decrease in NO generation (11.334 +/- 0.467 micromol vs 7.978 +/- 0.334 micromol P < 0.01 for NOx; 8.986 +/- 1.351 micromol vs 6.854 +/- 0.460 micromol for nitrotyrosine P < 0.01) and nNOS activity (decreased to 43% P<0.05). This function was abolished by the co-administration of quercetin.
The antioxidant action of quercetin relies, in part, on its ability to stimulate nNOS and enhance production of NO that would interact with endogenously produced reactive oxygen to inhibit hyper-proliferation of gastric mucosal cells in rats treated with chronic oral ethanol.
研究人体饮食中的主要类黄酮槲皮素（3,3',4',5,7 - 五羟基黄酮）对慢性口服乙醇处理的大鼠胃黏膜细胞过度增殖的影响。
将40只体重200 - 250 g的雄性Sprague - Dawley大鼠随机分为对照组（自由饮用自来水）、乙醇处理组（6 mL/L乙醇）、槲皮素处理组（每天100 mg/kg槲皮素灌胃）和乙醇加槲皮素处理组（槲皮素和6 mL/L乙醇）。通过蛋白质免疫印迹法检测增殖细胞核抗原（PCNA）和细胞周期蛋白D1的表达水平，以测定大鼠胃黏膜细胞增殖情况。为证明槲皮素对大鼠细胞外活性氧/氮物种（ROS/RNS）产生的影响，测定硫代巴比妥酸反应性物质（TBARS）、蛋白质羰基、亚硝酸盐和硝酸盐（NOx）以及硝基酪氨酸（NT）水平的变化。还通过蛋白质免疫印迹法检测诱导型一氧化氮合酶（NOS）包括诱导型一氧化氮合酶（iNOS）和神经元型一氧化氮合酶（nNOS）的活性。
与对照动物相比，接受乙醇处理7天的动物胃黏膜细胞增殖显著增加（PCNA密度增加至290%，P < 0.05；细胞周期蛋白D1密度增加至150，P < 0.05；每个视野PCNA阳性细胞为21.6±0.8对42.3±0.7），同时ROS生成增加（TBARS为1.298±0.135 μmol对1.772±0.078 μmol，P < 0.05；羰基含量为4.36±0.39 mmol对7.48±0.40 mmol，P < 0.05），NO生成减少（NOx为11.334±0.467 μmol对7.978±0.334 μmol，P < 0.01；硝基酪氨酸为8.986±1.351 μmol对6.854±0.460 μmol，P < 0.01）以及nNOS活性降低（降低至43%，P < 0.05）。同时给予槲皮素可消除此作用。
槲皮素的抗氧化作用部分依赖于其刺激nNOS并增强NO生成的能力，NO会与内源性产生的活性氧相互作用，从而抑制慢性口服乙醇处理的大鼠胃黏膜细胞的过度增殖。
