白藜芦醇对高糖诱导肾小球内皮细胞损伤的调节作用及分子机制

Regulatory effect and molecular mechanism of resveratrol on high glucose induced glomerular endothelial cell injury

目的 研究白藜芦醇(Res)对高糖诱导肾小球内皮细胞损伤的调节作用及分子机制。方法 培养人肾小球内皮细胞(HRGEC)并随机分为含有5.5 mmol/L葡萄糖培养基处理的对照组,含有30 mmol/L葡萄糖培养基处理的高糖组,含有不同浓度Res(25μmol/L、50μmol/L、100μmol/L)及30 mmol/L葡萄糖培养基处理的Res-L组、Res-M组、Res-H组。检测细胞活力A水平、细胞凋亡率、细胞中沉默信息调节因子1(Sirt1)、cleaved caspase-3、乙酰化p53、乙酰化NF-κB表达水平及培养基中肿瘤坏死因子-α(TNF-α)、白介素(IL)-1β、IL-6的含量。结果 高糖组的A水平、细胞中Sirt1表达水平低于对照组,凋亡率、cleaved caspase-3、乙酰化p53、乙酰化NF-κB表达水平及TNF-α、IL-1β、IL-6高于对照组(P<0.05);Res-L组、Res-M组、Res-H组的A水平、细胞中Sirt1表达水平高于高糖组,凋亡率、cleaved caspase-3、乙酰化p53、乙酰化NF-κB表达水平及TNF-α、IL-1β、IL-6低于高糖组(P<0.05),且Res剂量越高,上述变化越显著。结论 Res对高糖诱导HRGEC损伤具有保护作用,促进p53及NF-κB去乙酰化、抑制凋亡及炎症反应是与之相关的分子机制。

Objective To study the regulatory effect and molecular mechanism of resveratrol (Res) on high glucose induced glomerular endothelial cell injury.Methods Human glomerular endothelial cell(HRGEC) were cultured and randomly divided into the control group treated with medium containing 5.5mmol/L glucose and the high glucose group treated with medium containing 30 mmol/L glucose.Res-L group,Res-M group and Res-H group were treated with medium containing different concentration(25μmol/L,50μmol/L,100μmol/L Res) and 30 mmol/L glucose.After 24 h treatment,cell viability Alevel,apoptosis rate,the expression levels of Sirt1,cleaved caspase-3,acetylated p53 and acetylated NF-κB,the contents of tumor necrosis factor-α(TNF-α),Interleukin (IL)-1β,IL-6 in culture medium were detected.Results The Alevel and SIRT1 expression level of high glucose group were lower than those in the control group,and the apoptosis rate,the expression levels of cleaved caspase-3,acetylated p53 and acetylated NF-κB and the contents of TNF-α,IL-1β,IL-6 were higher than those in the control group (P<0.05).The Alevel and SIRT1 expression level of Res-L group,Res-M group and Res-H group were higher than those of high glucose group,and the apoptosis rate,the expression levels of cleaved caspase-3,acetylated p53 and acetylated NF-κB and the contents of TNF-α,IL-1 β,IL-6 were lower than those of high glucose group(P<0.05),and the higher the Res dose was,the more significant the above changes were.Conclusion Res has a protective effect on high glucose HRGEC injury induced and promotes the deacetylation of p53 and NF-κB,inhibits the apoptosis and inflammatory response are the related molecular mechanisms.