金合欢素调节Sirt1/AMPK/Nrf2信号通路对糖尿病白内障大鼠氧化应激损伤的影响  

Effect of acacetin on oxidative stress injury in diabetic cataract rats by regulating sirtuin 1/adenosine monophosphate-activated protein kinase/nuclear factor-erythroid 2-related factor 2 signaling pathway

作　　者：罗元元[1] 曹静洁 王海营[1] 封传 唐陶富[1] 胡洁[1] LUO Yuanyuan;CAO Jingjie;WANG Haiying;FENG Chuan;TANG Taofu;HU Jie(College of Medical Technology,Yongzhou Vocational and Technical College of Hunan Province,Yongzhou 425000,Hunan Province,China;Department of Ophthalmology,Xiangya Hospital,Central South University,Changsha 410005,Hunan Province,China)

机构地区：[1]湖南省永州职业技术学院医学技术学院,湖南省永州市425000 [2]中南大学湘雅医院眼科,湖南省长沙市410005

出　　处：《眼科新进展》2024年第6期433-437,共5页Recent Advances in Ophthalmology

基　　金：湖南省自然科学科教联合基金项目(编号:2019JJ70039)。

摘　　要：目的探讨金合欢素对糖尿病白内障(DC)大鼠氧化应激损伤的影响及其对沉默调节蛋白1(Sirt1)/腺苷酸活化蛋白激酶(AMPK)/核因子E2相关因子2(Nrf2)信号通路的调控作用。方法60只SD大鼠随机分为对照组、模型组、金合欢素低剂量组、金合欢素高剂量组、金合欢素+Sirt1抑制剂(EX527)组,除对照组以外均构建DC大鼠模型,其中,金合欢素低剂量组、金合欢素高剂量组大鼠分别经颈部皮下注射10 mg·kg^(-1)、20 mg·kg^(-1)的金合欢素,金合欢素+EX527组大鼠经颈部皮下注射20 mg·kg^(-1)金合欢素,均为每天2次,同时金合欢素+EX527组大鼠经皮下埋入渗透微型泵每天泵入3.5 mg·kg^(-1)EX527,其余组别均泵入等量生理盐水,给药持续4周。给药结束后,测量血压和空腹血糖(FBG),裂隙灯照射法观察大鼠晶状体混浊状况,HE染色观察晶状体组织病理学变化,ELISA测定血清丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、白细胞介素(IL)-6、IL-1β的含量,Western blot检测Sirt1、p-AMPK、AMPK、Nrf2蛋白表达水平。结果与对照组相比,模型组大鼠晶状体上皮细胞呈片状、条索状,发生迁移性聚集,收缩压、FBG、晶状体混浊评分、MDA、IL-6、IL-1β水平均升高,SOD、GSH-Px含量及Sirt1、p-AMPK/AMPK、Nrf2蛋白表达水平均降低(均为P<0.05);与模型组比较,金合欢素低、高剂量组大鼠晶状体上皮细胞迁移性聚集现象改善,收缩压、FBG、晶状体混浊评分、MDA、IL-6、IL-1β水平均降低,SOD、GSH-Px含量及Sirt1、p-AMPK/AMPK、Nrf2蛋白表达水平均升高(均为P<0.05);与金合欢素高剂量组比较,金合欢素+EX527组晶状体上皮细胞形态改变和聚集现象加重,收缩压、FBG、晶状体混浊评分、MDA、IL-6、IL-1β水平均升高,SOD、GSH-Px含量及Sirt1、p-AMPK/AMPK、Nrf2蛋白表达水平均降低(均为P<0.05)。结论金合欢素可能通过激活Sirt1/AMPK/Nrf2通路保护DC大鼠免受氧化应激Objective To investigate the effect of acacetin on oxidative stress injury in diabetic cataract(DC)rats and its regulation of sirtuin 1(Sirt1)/adenosine monophosphate-activated protein kinase(AMPK)/nuclear factor-erythroid 2-related factor 2(Nrf2)signaling pathway.Methods Sixty SD rats were randomly divided into the control group,model group,low-dose acacetin group,high-dose acacetin group,and acacetin+Sirt1 inhibitor(EX527)group.DC rat models were constructed except for the control group.Rats in the low-dose and high-dose acacetin groups were injected with 10 mg·kg^(-1)and 20 mg·kg^(-1)acacetin subcutaneously through the neck,twice a day,respectively.Rats in the acacetin+EX527 group were injected with 20 mg·kg^(-1)acacetin subcutaneously through the neck,twice a day;additionally,3.5 mg·kg^(-1)EX527 was administered subcutaneously through the osmotic micro-pump for 4 weeks.The same amount of normal saline was pumped into rats in the rest groups for 4 weeks.After administration,blood pressure and fasting blood glucose(FBG)were measured.The lens opacity was observed under the slit lamp irradiation,and the histopathological changes in the lens were observed after hematoxylin-eosin staining.Enzyme-linked immunosorbent assay was performed to determine the serum levels of malondialdehyde(MDA),superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),interleukin(IL)-6,and IL-1β.Western blot was applied to detect the expression levels of Sirt1,phosphorylated AMPK(p-AMPK),AMPK,and Nrf2 proteins.Results Compared with the control group,the lens epithelial cells(LECs)of rats in the model group showed patchy and striped shapes,and migration and aggregation occurred;the systolic blood pressure(SBP),FBG,lens opacity score,and the levels of MDA,IL-6 and IL-1βincreased,while the expression levels of SOD,GSH-Px,Sirt1,p-AMPK/AMPK,and Nrf2 proteins decreased(all P<0.05).Compared with the model group,the migration and aggregation of LECs improved in the low-dose and high-dose acacetin groups,the SBP,FBG,lens opacity score,and th

关 键 词：金合欢素 糖尿病白内障 氧化应激损伤 沉默调节蛋白1/腺苷酸活化蛋白激酶/核因子E2相关因子2信号通路 

分 类 号：R776.1[医药卫生—眼科]