PEDF Attenuates Ocular Surface Damage in Diabetic Mice Model Through Its Antioxidant Properties

PEDF Attenuates Ocular Surface Damage in Diabetic Mice Model Through Its Antioxidant Properties
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PEDF 通过其抗氧化特性减轻糖尿病小鼠模型的眼表损伤

DOI:
10.1080/02713683.2020.1805770
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发表时间:
2020-08
影响因子:
2
通讯作者:
Shaozhen Zhao
Shaozhen Zhao
中科院分区:
医学4区
文献类型:
--
作者:
Xuemei Liu;Hui Liu;Xiaoxiao Lu;Joyce Tombran-Tink;Shaozhen Zhao

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摘要目的探讨色素上皮衍生因子(PEDF)对糖尿病小鼠眼表损伤的抗氧化作用及其机制。方法C57 BL/6小鼠腹腔注射链脲佐菌素建立糖尿病模型,分别给予50 nM PEDF或人工泪液治疗。每天给药三次,持续八周。角膜上皮损伤、角膜敏感性和泪液量分别通过荧光素染色、触觉计和酚红棉线进行定量。糖尿病后16周处死动物,取整个地球仪标本进行组织化学染色。用2 ′,7-二氯二氢荧光素探针检测活性氧(ROS)的产生。采用实时荧光定量PCR和Western blotting方法检测晚期糖基化终产物受体(receptor for advanced glycation end products,RECEPTOR)和超氧化物歧化酶1(superoxidedismutase 1,SOD 1)的表达。结果局部应用PEDF可改善糖尿病小鼠角膜上皮损伤,提高角膜敏感性,增加泪液量。糖尿病小鼠角膜中的ROS水平显著高于正常小鼠。此外,PEDF减弱了ROS的积累,降低了角膜中ROS的表达,并提高了角膜中SOD 1的表达。结论局部应用PEDF可减轻糖尿病相关眼表损害,增加泪液量,沿着氧化应激状态的改善。
ABSTRACT Purpose To investigate the antioxidative effect and mechanism of pigment epithelium-derived factor (PEDF) on the ocular surface damage in diabetic mice. Methods C57BL/6 mice were injected intraperitoneally with streptozocin to generate diabetic models and then 50 nM PEDF or artificial tears were used to treat the diabetic mice. Treatment was given three times a day for eight weeks. Corneal epithelial damage, corneal sensitivity, and tear volume were quantified by fluorescein staining, esthesiometer, and phenol red cotton thread, respectively. Animals were sacrificed at 16 weeks after diabetes and the whole globe specimens were subjected to histochemical staining. Reactive oxygen species (ROS) generation was detected by 2ʹ,7-dichlorodihydrofluorescein probe. The levels of receptor for advanced glycation end products (RAGE) and superoxide dismutase 1 (SOD1) were examined by quantitative real-time PCR and western blotting. Results Topical application of PEDF improved corneal epithelial damage, increased corneal sensitivity, and tear volume in diabetic mice. ROS levels in the cornea were significantly higher in the diabetic mice than in the normal mice. Moreover, PEDF attenuated the accumulation of ROS, decreased the expression of RAGE, and elevated SOD1 expression in the cornea. Conclusions Topical application of PEDF can alleviate diabetes-related ocular surface damage and increase tear volume, along with the improvement of oxidative stress status.
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发表时间: 2018-03-02
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