地塞米松对高糖诱导肾小球足细胞氧化损伤的作用机制  

Mechanism of dexamethasone against high glucose-induced oxidative damage to glomerular podocytes

作　　者：蒋一凡 耿煜 张新 左中夫 Jiang Yifan;Geng Yu;Zhang Xin;Zuo Zhongfu(Panjin Liaoyou Baoshihua Hospital,Panjin 124010,Liaoning Province,China;Affiliated Hospital of Jinzhou Medical University,Jinzhou 121012,Liaoning Province,China)

机构地区：[1]盘锦辽油宝石花医院,辽宁省盘锦市124010 [2]锦州医科大学附属医院,辽宁省锦州市121012

出　　处：《中国组织工程研究》2023年第24期3852-3857,共6页Chinese Journal of Tissue Engineering Research

基　　金：辽宁省自然科学基金项目(2019-ZD-0807),项目负责人:左中夫。

摘　　要：背景:地塞米松是近年来临床常用的治疗糖尿病肾病的糖皮质激素药物,其可直接作用于肾小球足细胞,通过抑制炎症反应、稳定细胞周期等来增加肾小球足细胞的存活率,但其具体作用机制尚不明确。目的:探讨地塞米松对高糖诱导的肾小球足细胞氧化损伤的作用机制。方法:取肾小球足细胞,分6组处理:A组常规培养,不进行处理;B组加入葡萄糖处理;C组加入葡萄糖处理48 h,随后加入缬沙坦处理24 h;D-F组加入葡萄糖处理48 h,随后分别加入1×10^(-7),1×10^(-6),1×10^(-5) mol/L的地塞米松处理24 h。处理结束后,采用巢式降落式特异性PCR检测各组细胞抑制轴突生长受体基因甲基化水平,MTT法检测细胞增殖,流式细胞仪检测细胞凋亡,化学发光法氧化损伤相关指标,免疫荧光法检测过氧化物酶体增殖物激活受体γ表达。结果与结论:(1)与A组比较,B组抑制轴突生长受体基因甲基化水平、细胞凋亡、丙二醛水平升高(P<0.05),细胞增殖、超氧化物歧化酶与谷胱甘肽水平、过氧化物酶体增殖物激活受体γ表达降低(P<0.05);(2)与B组比较,C组抑制轴突生长受体基因甲基化水平、细胞凋亡、丙二醛水平降低(P<0.05),细胞增殖、超氧化物歧化酶与谷胱甘肽水平、过氧化物酶体增殖物激活受体γ表达升高(P<0.05);(3)与C组比较,E、F组抑制轴突生长受体基因甲基化水平、细胞凋亡、丙二醛水平降低(P<0.05),细胞增殖、超氧化物歧化酶与谷胱甘肽水平、过氧化物酶体增殖物激活受体γ表达升高(P<0.05),并且F组改变程度大于E组(P<0.05);D组各指标与C组比较差异均无显著性意义(P>0.05);(4)结果表明,地塞米松可显著改善高糖诱导的肾小球足细胞氧化损伤,促进过氧化物酶体增殖物激活受体γ表达,其机制可能与阻止抑制轴突生长受体基因甲基化有关。BACKGROUND:Dexamethasone is a glucocorticoid drug commonly used for treating diabetic nephropathy in recent years.It can directly act on glomerular podocytes and increase cell survival by inhibiting inflammato ry response and stabilizing cell cycle.Howeve r,its specific mechanism of action remains unclear.OBJECTIVE:To investigate the mechanism of dexamethasone on high glucose-induced oxidative damage to glomerular podocytes.METHODS:Glomerular podocytes were divided into six groups:group A,r outine culture with no treatment;group B,treatment with glucose;group C,treatment with glucose for 48 hours and valsartan for another 24 hours;groups D-F,treatment with glucose for 48 hours and 1×10^(-7),1×10^(-6),1×10^(-5) mol/L dexamethasone for another 24 hours,res pectively.Specific touchdown nested PCR was used to detect the methylation level of N ogo receptor 1(NgR1)in cells.MTT method was used to detect cell proliferation.Flow cytometry was used to detect cell apoptosis.Chemiluminescence method was used to detect oxidative damage-related indicato rs.Immunofluorescence method was used to detect peroxisome prolife rator-activated receptorγexpression.RESULTS AND CONCLUSION:(1)Compared with group A,group B had significantly increased methylation level of NgR1,cell apoptosis,and malondialdehyde level(P<0.05),but significantly decreased cell proliferation,supe roxide dismutase and glutathione levels,and pe roxisome proliferator-activated receptorγexpression(P<0.05).(2)Compared with group B,group C had significantly decreased methylation level of NgR1,cell apoptosis,and malondialdehyde level(P<0.05),but significantly increased cell proliferation,supe roxide dismutase and glutathione levels,and peroxisome proliferator-activated receptor y expression(P<0.05).(3)Compared with group C,groups E and F had significantly decreased methylation level of NgR1,cell apoptosis,and malondialdehyde level(P<0.05),but significantly increased cell proliferation,superoxide dismutase and glutathione levels,and peroxisome proliferator-activate

关 键 词：肾小球足细胞 高糖损伤 地塞米松 抑制轴突生长受体基因甲基化 氧化损伤 过氧化物酶体增殖物激活受体Γ 

分 类 号：R453.9[医药卫生—治疗学] R364.7[医药卫生—临床医学] R587.2