槲皮苷通过增强Nrf-2/HO-1信号通路改善亚硒酸盐所致的大鼠白内障

Quercitrin Alleviates Selenite-induced Cataract in Rats by Enhancing Nrf-2/HO-1 Signaling Pathway

关键词:  槲皮苷  亚硒酸盐  白内障  氧化应激

Key words:  quercetin  selenite  cataract  oxidative stress

摘要:

目的 探究槲皮苷对亚硒酸钠（selenite，Se）所致的大鼠白内障的治疗作用及其机制。方法 将11 d龄SD仔鼠随机分为对照组、模型组、低剂量槲皮苷组和高剂量槲皮苷组，每组10只。造模后第15天，检查各组大鼠的白内障形成情况。分离晶状体，采用HE染色观察晶状体病理学表现；采用试剂盒法测定晶状体中可溶和不可溶蛋白含量、丙二醛（malondialdehyde，MDA）含量以及超氧化物歧化酶（superoxide dismutase，SOD）、谷胱甘肽过氧化物酶（glutathione peroxidase，GSH-Px）和谷胱甘肽还原酶（glutathione reductase，GSH-Rd）活性；采用免疫荧光染色法和Western blotting检测晶状体中核因子E2相关因子2（nuclear nuclear factor E2-related factor 2，Nrf-2）和血红素加氧酶1（cytoplasmic heme oxygenase 1，HO-1）蛋白表达水平。结果 与对照组比较，模型组晶状体形态发生明显改变，晶状体的混浊积分、不溶性蛋白和MDA含量均明显增加（P<0.01），而可溶性蛋白含量、SOD、GSH-Px和GSH-Rd活性明显降低（P<0.01）；与模型组比较，槲皮苷组上述情况均得到明显改善（P<0.05或P<0.01），尤其在高剂量组（P<0.01）。免疫荧光结果显示，与对照组比较，模型组晶状体中Nrf-2和HO-1蛋白表达水平均明显增加（P<0.01），用槲皮苷处理后Nrf-2和HO-1蛋白表达水平进一步增加。Western blotting检测显示，与模型组比较，槲皮苷组晶状体中Nrf-2核转位增多且总Nrf-2和HO-1蛋白水平均明显增加（P<0.01）。结论 槲皮苷能抑制Se诱导的大鼠白内障生成和氧化应激反应，且这些作用可能与其增强Nrf-2/HO-1信号活性有关。

Abstract:

OBJECTIVE To explore the therapeutic effect and mechanism of quercetin on selenite(Se)-induced cataract model in rats. METHODS SD rats aged 11 d were randomly divided into control group, model group, low-dose quercetin group and high-dose quercetin group with 10 rats in each group. On the 15th day after modeling, cataract formation in each group was examined. The lens was separated and the pathological manifestations of lens were observed by HE staining. The contents of soluble and insoluble protein, malondialdehyde(MDA), and the activities of superoxide dismutase(SOD), glutathione peroxidase(GSH-Px) and glutathione reductase(GSH-Rd) in lens were determined by kits' methods. The expression levels of nuclear nuclear factor E2-related factor 2(Nrf-2) and cytoplasmic heme oxygenase 1(HO-1) in lens were detected by Western blotting. RESULTS Compared with control group, the morphology of lens in model group was significantly changed, and the score of lens opacification, contents of insoluble protein and MDA were significantly increased(P<0.01), while the contents of soluble protein, activities of SOD, GSH-Px and GSH-Rd were significantly decreased(P<0.01); compared with model group, the above conditions in quercetin groups were significantly improved(P<0.05 or P<0.01), especially in the high-dose group(P<0.01). Immunofluorescence results showed that compared with the control group, the protein expression levels of Nrf-2 and HO-1 in the lens of model group were significantly increased(P<0.01) and the protein expression levels of Nrf-2 and HO-1 were further increased after treated with quercetin. Western blotting showed that compared with the model group, the nuclear translocation of Nrf-2 and the protein levels of total Nrf-2 and HO-1 were significantly increased in the quercetin groups(P<0.01). CONCLUSION Quercetin can inhibit the formation of cataract and oxidative stress response induced by Se in rats, and these effects may be related to the enhancement of Nrf-2/HO-1 signal activity.