葡萄籽原花青素激活Xc^(-)/GPX4通路抑制铁死亡改善大鼠糖尿病肾病  

Activation of Xc-/GPX4 Pathway by Grape Seed Procyanidin Extract Inhibit Ferroptosis to Ameliorate Diabetic Nephropathy in Rats

作　　者：陆恒 杨瑞瑞 王浩 李海燕 王同玲 张丽媛 丁玉松[1] LU Heng;YANG Rui-rui;WANG Hao;LI Hai-yan;WANG Tong-ling;ZHANG Li-yuan;DINGYu-song(Department of Public Health,Shihezi University School of Medicine,Xinjiang Shihezi,83202)

机构地区：[1]石河子大学医学院预防医学系,新疆石河子832002

出　　处：《农垦医学》2023年第6期488-493,557,共7页Journal of Nongken Medicine

基　　金：新疆生产建设兵团财政科技计划项目(2021AB030)。

摘　　要：目的:探讨葡萄籽原花青素能否通过激活Xc-/GPX4通路抑制铁死亡改善大鼠糖尿病肾病。方法:将45只SD大鼠随机分配10只到对照组,其他大鼠进行糖尿病肾病造模,随后随机分配为DN组、GSPE组以及Fer-1组。GSPE组和Fer-1组分别以葡萄籽原花青素(Grape Seed Procyanidin Extract, GSPE)以及Ferrostatin-1(Fer-1)干预。检测肾功能指标、氧化抗氧化指标,同时用Masson、Lillie染色检测肾纤维化及Fe2+,用Western Blot检测肾脏纤维化以及铁死亡相关蛋白。结果:与对照组相比,DN组大鼠肾脏功能出现明显损伤(P<0.05),纤维原沉积明显,Fe2+增加,细胞发生铁死亡,且Xc系统蛋白显著降低(P<0.05)。与DN组相比,GSPE和铁死亡抑制剂Fer-1干预之后上述指标均有所改善(P<0.05)。结论:葡萄籽原花青素通过激活Xc-/GPX4通路抑制铁死亡改善大鼠糖尿病肾病。Objective:To investigate whether grape seed procyanidin extract can improve diabetic nephropathy in rats by activating Xc-/GPX4 pathway to inhibit ferroptosis.Methods:Ten of 45 SD rats were randomly assigned to the control group,and other rats were modeled with diabetic nephropathy.As a successful model,and then randomly assigned to DN group,GSPE group and Fer-1 group.GSPE group and Fer-1 group were treated with grape seed procyanidin extract(GSPE)and Ferrostatin-1(Fer-1),respectively.The renal function indexes and oxidation resistance indexes were detected,renal fibrosis and Fe2+were detected by Masson and Lillie staining,renal fibrosis and ferroptosis-related proteins were detected with Western Blot.Results:Compared with the control group,the kidney function of rats in the DN group was obviously damaged(P<0.05),the deposition of fibrinogen was obvious,Fe2+was increased,ferroptosis occurred in the cells,and system Xc protein was significantly decreased(P<0.05).Compared with DN group,GSPE and ferroptosis inhibitor Fer-1 intervention improved the above indexes(P<0.05).Conclusion:Grape seed procyanidin extract improve diabetic nephropathy in rats by activating Xc-/GPX4 pathway to inhibit ferroptosis.

关 键 词：铁死亡 糖尿病肾病 Xc-/GPX4 葡萄籽原花青素 

分 类 号：R587.2[医药卫生—内分泌] R285.5[医药卫生—内科学]