Age-related eye diseases,including cataract,glaucoma,diabetic retinopathy(DR),and age-related macular degeneration(AMD),are the leading causes of vision loss in the world.Several studies have shown that the occurrence...Age-related eye diseases,including cataract,glaucoma,diabetic retinopathy(DR),and age-related macular degeneration(AMD),are the leading causes of vision loss in the world.Several studies have shown that the occurrence and development of these diseases have an important relationship with oxidative stress in the eye.The Keap1-Nrf2-ARE pathway is a classical pathway that resists oxidative stress and inflammation in the body.This pathway is also active in the development of age-related eye diseases.A variety of drugs have been shown to treat agerelated eye diseases through the Keap1-Nrf2-ARE(Kelch-like ECH-Associating protein 1-nuclear factor erythroid 2 related factor 2-antioxidant response element)pathway.This review describes the role of oxidative stress in the development of age-related eye diseases,the function and regulation of the Keap1-Nrf2-ARE pathway,and the therapeutic effects of drugs associated with this pathway on age-related eye diseases.展开更多
目的基于Kelch样相关蛋白1-核因子E2相关因子-抗氧化反应元件信号通路(Keap1-Nrf2-ARE)及下游Maf、γ-谷氨酰半胱氨酸合成酶(γ-GCS)、血红素加氧酶(HO-1)蛋白表达探讨加味天雄散调节弱精症大鼠精子活力的作用机制。方法清洁级SD雄性大...目的基于Kelch样相关蛋白1-核因子E2相关因子-抗氧化反应元件信号通路(Keap1-Nrf2-ARE)及下游Maf、γ-谷氨酰半胱氨酸合成酶(γ-GCS)、血红素加氧酶(HO-1)蛋白表达探讨加味天雄散调节弱精症大鼠精子活力的作用机制。方法清洁级SD雄性大鼠60只随机分为对照组、模型组、安慰剂组、治疗组,每组15只。采用腺嘌呤[100 mg/(100 g·d)]灌胃10天造模,对照组灌胃等量生理盐水。造模结束后治疗组予以加味天雄散中药灌服,安慰剂组给予等量生理盐水,连续灌胃30天。RT-PCR检测附睾组织Keap1、Nrf2 m RNA表达;Western Blot检测附睾组织Keap1、Nrf2、Maf、γ-GCS、HO-1蛋白表达;检测附睾组织超氧化物歧化酶(SOD)、丙二醛(MDA)水平。结果与对照组比较,模型组Keap1 m RNA及蛋白表达、MDA水平升高(P<0.01),Nrf2m RNA、Nrf2、Maf、γ-GCS、HO-1蛋白表达及SOD水平降低(P<0.01)。与模型组和安慰剂组比较,治疗组Keap1m RNA及蛋白表达、MDA水平降低(P<0.01),Nrf2 m RNA、Nrf2、Maf、γ-GCS、HO-1蛋白表达及SOD水平升高(P<0.01)。结论加味天雄散能够通过调节弱精子症大鼠精子Keap1-Nrf2-ARE通路及下游Maf、γ-GCS、HO-1蛋白表达,调控氧化应激反应,从而改善精子活力。展开更多
基金Supported by National Natural Science Foundation of China(No.81970801No.81670859)+1 种基金Natural Science Foundation of Hunan Province(No.2019JJ40001)Key Project of Changsha Science and Technology Bureau(No.kh1801229)。
文摘Age-related eye diseases,including cataract,glaucoma,diabetic retinopathy(DR),and age-related macular degeneration(AMD),are the leading causes of vision loss in the world.Several studies have shown that the occurrence and development of these diseases have an important relationship with oxidative stress in the eye.The Keap1-Nrf2-ARE pathway is a classical pathway that resists oxidative stress and inflammation in the body.This pathway is also active in the development of age-related eye diseases.A variety of drugs have been shown to treat agerelated eye diseases through the Keap1-Nrf2-ARE(Kelch-like ECH-Associating protein 1-nuclear factor erythroid 2 related factor 2-antioxidant response element)pathway.This review describes the role of oxidative stress in the development of age-related eye diseases,the function and regulation of the Keap1-Nrf2-ARE pathway,and the therapeutic effects of drugs associated with this pathway on age-related eye diseases.
文摘目的基于Kelch样相关蛋白1-核因子E2相关因子-抗氧化反应元件信号通路(Keap1-Nrf2-ARE)及下游Maf、γ-谷氨酰半胱氨酸合成酶(γ-GCS)、血红素加氧酶(HO-1)蛋白表达探讨加味天雄散调节弱精症大鼠精子活力的作用机制。方法清洁级SD雄性大鼠60只随机分为对照组、模型组、安慰剂组、治疗组,每组15只。采用腺嘌呤[100 mg/(100 g·d)]灌胃10天造模,对照组灌胃等量生理盐水。造模结束后治疗组予以加味天雄散中药灌服,安慰剂组给予等量生理盐水,连续灌胃30天。RT-PCR检测附睾组织Keap1、Nrf2 m RNA表达;Western Blot检测附睾组织Keap1、Nrf2、Maf、γ-GCS、HO-1蛋白表达;检测附睾组织超氧化物歧化酶(SOD)、丙二醛(MDA)水平。结果与对照组比较,模型组Keap1 m RNA及蛋白表达、MDA水平升高(P<0.01),Nrf2m RNA、Nrf2、Maf、γ-GCS、HO-1蛋白表达及SOD水平降低(P<0.01)。与模型组和安慰剂组比较,治疗组Keap1m RNA及蛋白表达、MDA水平降低(P<0.01),Nrf2 m RNA、Nrf2、Maf、γ-GCS、HO-1蛋白表达及SOD水平升高(P<0.01)。结论加味天雄散能够通过调节弱精子症大鼠精子Keap1-Nrf2-ARE通路及下游Maf、γ-GCS、HO-1蛋白表达,调控氧化应激反应,从而改善精子活力。
