橙皮苷在低压低氧所致大鼠视网膜抗氧化能力和炎症介质调控改变中的作用

目的　探讨橙皮苷（HSD）在低压低氧所致大鼠视网膜抗氧化应激能力及炎性介质调控改变中的干预作用。方法　取健康雄性清洁级成年SD大鼠72只（144眼），随机分为对照组、低压低氧组及HSD干预组，每组24只（48眼）。对照组大鼠饲养于常氧环境，低压低氧组及HSD干预组大鼠放置于模拟海拔5000 m高度的低压氧舱内喂养。HSD干预组大鼠给予HSD灌胃，对照组和低压低氧组大鼠给予生理盐水，各组大鼠每天等量灌胃一次，连续7 d。通过HE染色光镜下观察大鼠视网膜组织形态变化；采用酶联免疫吸附(ELISA)法检测大鼠视网膜谷胱甘肽(GSH)和半胱氨酸(Cys)蛋白浓度、丙二醛（MDA）含量以及肿瘤坏死因子-α（TNF-α）活性；Western-blot检测大鼠视网膜核因子-κB p65（NF-κB p65）和细胞色素C（Cyto-C)蛋白表达水平。结果　光镜下观察可见，与对照组相比，低压低氧组大鼠出现视网膜水肿，HSD干预组较低压低氧组大鼠视网膜水肿程度减轻。与对照组相比，低压低氧组大鼠视网膜中GSH蛋白浓度和Cys蛋白浓度降低，MDA含量升高，差异均有统计学意义（均为P<0.001）；与低压低氧组相比，HSD干预组提高了GSH蛋白浓度和Cys蛋白浓度，降低了MDA含量，GSH蛋白浓度和MDA含量两组相比差异均有统计学意义（均为P<0.001），Cys蛋白浓度两组相比差异无统计学意义（P>0.05）。与对照组相比，低压低氧组大鼠视网膜中NF-κB p65蛋白表达水平和TNF-α活性升高，差异均有统计学意义（P<0.01、 P<0.001）；与低压低氧组相比，HSD干预组大鼠视网膜中NF-κB p65蛋白表达水平和TNF-α活性降低，差异均有统计学意义（P<0.05、P<0.001）。与对照组相比，低压低氧组大鼠视网膜Cyto-C蛋白表达水平明显升高，差异有统计学意义（P<0.01）；与低压低氧组相比，HSD干预组大鼠视网膜中Cyto-C蛋白表达水平降低，差异有统计学意义（P<0.05）。结论　HSD能够通过提高大鼠视网膜抗氧化应激能力、抑制炎症介质释放以及减少线粒体损伤而发挥保护视网膜功能的作用。

Effect of hesperidin on hypobaric hypoxia-induced alterations of anti-oxidant capacity and inflammatory mediators release in rat retinas

Objective　To evaluate the effect of hesperidin (HSD) on rat retinal oxidative stress damage and inflammatory mediators release triggered by hypobaric hypoxia. Methods　A total of 72 healthy male SD rats (144 eyes) were randomly divided into the control group, hypobaric hypoxia (HH) group, and HSD group, with 24 rats (48 eyes) in each group. Rats in the control group were housed in normal conditions, while rats in the HH and HSD groups were housed in a HH chamber at a simulated altitude of 5,000 meters. In addition, rats in the HSD group were given HSD intragastrically, and rats in the control group and the HH group were given normal saline in the same way. All rats were administered with an equivalent dosage once a day for seven days continuously. Retinal morphological changes were detected via hematoxylin and eosin staining and microscopic observation. Enzyme-linked immunosorbent assay was performed to analyze the levels of glutathione (GSH), cysteine (Cys) and malondialdehyde (MDA) and the activity of tumor necrosis factor-α (TNF-α). Western blot was used to determine the protein expression levels of nuclear factor kappa B p65 (NF-κB p65) and cytochrome C (Cyto-C). Results　It was observed under a light microscope that compared with the control group, retinal edema occurred in the HH group, which was ameliorated following HSD intervention. The protein levels of GSH and Cys in the HH group were decreased, while the content of MDA was elevated compared with the control group (all P<0.001). HSD intervention enhanced the protein levels of GSH and Cys, and reduced the content of MDA compared with the HH group. Significant differences were seen in the GSH and MDA levels (both P<0.001), but no observed in the Cys level between the HSD and HH groups (P>0.05). Compared with the control group, the NF-κB p65 protein level and the TNF-α activity in the HH group were significantly increased (P<0.01, P<0.001); while compared with the HH group, the NF-κB p65 protein level and the TNF-α activity in the HSD group were significantly decreased (P<0.05, P<0.001). Compared with the control group, the Cyto-C protein level in the HH group was significantly increased (P<0.01); while compared with the HH group, the Cyto-C protein level in the HSD group was significantly reduced (P<0.05). Conclusion　HSD can protect the retina by enhancing the retinal ability against oxidative stress, inhibiting the release of inflammatory mediators and reducing mitochondrial injury.