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
目的探讨益气养阴活血方通过调控Kelch样ECH关联蛋白1(recombinant Kelch like ECH associated protein 1,Keap1)/核因子E2相关因子2(nuclear factor erythroid-2 related factor 2,Nrf2)/抗氧化反应原件(antioxidant response ele-ment...目的探讨益气养阴活血方通过调控Kelch样ECH关联蛋白1(recombinant Kelch like ECH associated protein 1,Keap1)/核因子E2相关因子2(nuclear factor erythroid-2 related factor 2,Nrf2)/抗氧化反应原件(antioxidant response ele-ment,ARE)信号通路对糖尿病肾病(diabetic nephropathy,DN)大鼠的肾脏保护作用机制。方法清洁级雄性SD大鼠50只,适应性喂养1周后,随机分为5组:空白组、模型组、缬沙坦(代文)组、益气养阴活血方等剂量(等剂量)组及高剂量(高剂量)组,每组10只。除空白组外各组均应用高脂高糖喂养,联合单次注射链脲佐菌素(streptozotocin,STZ)建立DN大鼠模型。除去造模失败5只,死亡5只,每组剩余8只。造模成功后空白组和模型组灌服生理盐水,中药两组均灌服益气养阴活血方颗粒剂,代文组按8.33mg·kg^(-1)·d^(-1)灌胃,6周后留取大鼠24小时尿液、血液和肾脏组织。生化检测各组大鼠24h尿总蛋白定量(24-UTP)、血肌酐(SCr)、血尿素氮(BUN)、白蛋白(ALB)、谷丙转氨酶(ALT)、葡糖糖(GLU)、总胆固醇(CHO)、甘油三酯(TG)、高密度脂蛋白(HDL);HE染色光镜观察肾组织病理改变;PCR法检测大鼠肾脏keap1、Nrf2、HO-1mRNA表达水平;蛋白免疫印迹(Western Blot)检测肾组织中keap1、Nrf2、HO-1蛋白水平;ELISA法检测血清Keap1、Nrf2、HO-1水平。结果生化指标:与空白组对比,模型组24hUTP、Scr、BUN、ALT、GLU、CHO及TG均明显升高(P<0.05或P<0.01),ALB、HDL明显降低(P<0.05);与模型组对比,代文组及中药两组24hUTP、Scr、BUN、ALT、GLU、CHO及TG均降低(P<0.05或P<0.01),ALB、HDL升高(P<0.05);与代文组对比,等剂量组、高剂量组BUN降低(P<0.05)。肾脏病理:与正常组对比,模型组大鼠肾脏组织多见肾小管上皮细胞气球样变性,可见胞质空泡化以及间质纤维化,并多见血管瘀血、扩张;与模型组对比,代文组及中药两组肾小管扩张、间质纤维化、血管瘀血等情况均有改善。PCR:与空白组对展开更多
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.
