橙皮素调节Keap1/Nrf2/ARE信号通路对D-半乳糖诱导的白内障大鼠氧化应激损伤的影响

doi:10.3969/j.issn.1006-6233.2023.02.04

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Abstract Objective: To explore the impact of hesperetin on D-galactose-induced oxidative stress injury in rats with cataract and its mechanism of regulating Keap1/Nrf2/ARE signaling pathway. Methods: Seventy-two SPF Wistar male rats were randomly separated into sham operation group, model group, positive group, low and high dose hesperetin groups, and high dose hesperetin + Nrf2 inhibitor ATRA group. Cataract rat models were established by subcutaneous injection of 200mg/kg of D-galactose in all groups except the sham-operation group. The positive control group was treated with fuming capsule (30mg/kg), the low and high dose groups were treated with hesperetin (50mg/kg, 150mg/kg) respectively, and the high dose +ATRA group was treated with hesperetin (100mg/kg) first, and then ATRA(10mg/kg) was injected intraperitoneally. Slit lamp was used to observe the degree of opacity of the lens tissue in both eyes; HE was applied to observe the morphological changes of lens epithelium in each group; TUNEL method was applied to detect the apoptosis rate of lens epithelial tissue; ELISA was applied to measure superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities in the lens; Western blotting was applied to detect the expression levels of Keap1, Nrf2, and HO-1 proteins in the lens. Results: Compared with the sham-operation group, the lens epithelial tissue of the model group had disordered cell arrangement, edema, and enlarged gaps, the degree of lens opacity, epithelial cell apoptosis rate, Keap1 and cytoplasmic Nrf2 protein expression increased (P<0.05), SOD, CAT, GSH-Px activity, nuclear Nrf2, HO-1 protein expressions decreased (P<0.05). Compared with the model group, the damage of the lens epithelium of the rats in the positive group and the low and high-dose hesperetin groups was alleviated, the degree of lens opacity, epithelial cell apoptosis rate, Keap1 and cytoplasmic Nrf2 protein expression decreased (P<0.05), SOD, CAT, GSH-Px activity, nuclear Nrf2, HO-1 protein expressions increased (P<0.05). The Nrf2 inhibitor ATRA could greatly attenuate the ameliorating effect of high-dose hesperetin on lens damage in cataract rats. Conclusion: Hesperetin can alleviate D-galactose-induced oxidative stress injury in cataract rats, which may be achieved by inhibiting the expression of Keap1 and promoting the activation of Nrf2/ARE pathway.

Key words： Hesperetin Keap1/Nrf2/ARE pathway D-galactose Cataract Oxidative stress

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http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2023.02.04 OR http://www.hbyxzzs.cn/EN/Y2023/V29/I2/195

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