[1]罗元元,曹静洁,王海营,等.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[J].眼科新进展,2024,44(6):433-437.[doi:10.13389/j.cnki.rao.2024.0084]
 LUO Yuanyuan,CAO Jingjie,WANG Haiying,et al.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[J].Recent Advances in Ophthalmology,2024,44(6):433-437.[doi:10.13389/j.cnki.rao.2024.0084]
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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/HTML
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《眼科新进展》[ISSN:1003-5141/CN:41-1105/R]

卷:
44卷
期数:
2024年6期
页码:
433-437
栏目:
实验研究
出版日期:
2024-06-03

文章信息/Info

Title:
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:
罗元元曹静洁王海营封传唐陶富胡洁
425000 湖南省永州市,湖南省永州职业技术学院医学技术学院(罗元元,王海营,封传,唐陶富,胡洁);410005 湖南省长沙市,中南大学湘雅医院眼科(曹静洁)
Author(s):
LUO Yuanyuan1CAO Jingjie2WANG Haiying1FENG Chuan1TANG Taofu1HU Jie1
1.College of Medical Technology,Yongzhou Vocational and Technical College of Hunan Province,Yongzhou 425000,Hunan Province,China
2.Department of Ophthalmology,Xiangya Hospital,Central South University,Changsha 410005,Hunan Province,China
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
Keywords:
acacetin diabetic cataract oxidative stress injury sirtuin 1/adenosine monophosphate-activated protein kinase/nuclear factor-erythroid 2-related factor 2 signaling pathway
分类号:
R776.1
DOI:
10.13389/j.cnki.rao.2024.0084
文献标志码:
A
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大鼠免受氧化应激损伤。
Abstract:
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-1β increased, 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 the levels of MDA, IL-6 and IL-1β decreased, while the expression levels of SOD, GSH-Px, Sirt1, p-AMPK/AMPK, and Nrf2 proteins increased (all P<0.05). Compared with the high-dose acacetin group, the morphological changes and aggregation of LECs in the acacetin+EX527 group were more significant, the SBP, FBG, lens opacity score, and the levels of MDA, IL-6 and IL-1β increased, while the expression levels of SOD, GSH-Px, Sirt1, p-AMPK/AMPK, and Nrf2 proteins decreased (all P<0.05).
Conclusion Acacetin may protect DC rats from oxidative stress injury by activating the Sirt1/AMPK/Nrf2 pathway.

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备注/Memo

备注/Memo:
湖南省自然科学科教联合基金项目(编号:2019JJ70039)
更新日期/Last Update: 2024-06-05