新疆鼠尾草酚酸类成分对HK-2细胞氧化损伤的保护作用及机制研究
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篇名: 新疆鼠尾草酚酸类成分对HK-2细胞氧化损伤的保护作用及机制研究
TITLE: Study on protective effect and mechanism of phenolic acid components from Salvia deserta Schang on oxidative injury of HK -2 cells
摘要: 目的 研究新疆鼠尾草酚酸类成分对高糖高脂诱导的人肾小管上皮细胞HK-2氧化损伤的保护作用,并初步探讨其可能机制。方法将HK-2细胞分为对照组、模型组、卡格列净片组(阳性对照组,15μmol/L)、新疆鼠尾草酚酸纯化物组(10.8μg/mL)和4个单体成分组(丹参素、原儿茶醛、咖啡酸、迷迭香酸,均为50μmol/L)。除对照组外,其余各组均建立高糖高脂损伤细胞模型(500μmol/L棕榈酸+30mmol/L葡萄糖处理48h)并加药培养48h。检测各组细胞的凋亡率以及细胞中丙二醛(MDA)、超氧化物歧化酶(SOD)含量和谷胱甘肽(GSH)活性,并检测上述5组(丹参素组、原儿茶醛组、咖啡酸组除外)细胞中核转录因子E2相关因子2(Nrf2)、Kelch样ECH相关蛋白1(Keap1)、血红素氧合酶1(HO-1)、醌NADH脱氢酶1(NQO1)蛋白的表达。结果与对照组比较,模型组细胞的凋亡率显著升高(P<0.01);细胞中MDA含量显著升高(P<0.01),GSH含量和SOD活性显著降低(P<0.01);细胞中Nrf2、NQO1、HO-1蛋白表达显著下调(P<0.01),Keap1蛋白表达显著上调(P<0.01)。与模型组比较,各给药组细胞的凋亡率及细胞中MDA含量均显著降低(P<0.01),各给药组细胞中GSH含量及酚酸纯化物组、原儿茶醛组、迷迭香酸组细胞中SOD活性均显著升高(P<0.01);酚酸纯化物组细胞中Nrf2、HO-1、NQO1蛋白表达以及迷迭香酸组Nrf2蛋白表达均显著上调(P<0.01),酚酸纯化物组和迷迭香酸组细胞中Keap1蛋白表达均显著下调(P<0.01)。结论新疆鼠尾草酚酸类成分可减轻高糖高脂所致肾小管上皮细胞的氧化应激损伤,其作用可能与其激活Keap1/Nrf2通路、抑制氧化应激反应相关。
ABSTRACT: OBJECTIVE To study the protective effect of phenolic acid components from Salvia deserta Schang on the oxidative stress injury of human renal tubular epithelial cells HK -2 induced by high glucose and high fat . METHODS HK-2 cells were divided into control group ,model group ,canagliflozin group (positive control group ,15 μmol/L),purified product of phenolic acids from S. deserta Schang group (10.8 μg/mL),4 monomers group (salvianic acid ,protocatechuic aldehyde ,caffeic acid,rosmarinic acid ,50 μmol/L). In addition to the control group ,cell injury model of high glucose and high fat was established in other groups (500 μmol/L palmitic acid+ 30 mmol/L glucose for 48 h)and cultured for 48 h. The cell apoptotic rate ,the contents of malondialdehyde (MDA)and glutathione (GSH),and the activity of superoxide dismutase (SOD)were detected in each group ; the expression levels of nuclear erythroid 2-related factor 2(Nrf2),Kelch-like ECH -associated protein 1(Keap1)protein,heme oxygenase-1(HO-1)and NADH :quinone acceptor oxidoreductase 1(NQO1)were determined in above 5 groups(except for salvianic acid ,protocatechuic aldehyde ,caffeic acid ). RESULTS Compared with control group ,the apoptotic rate of HK -2 cells in model group was increased significantly (P<0.01);the content of MDA was increased significantly (P<0.01),while the content of GSH and the activity of SOD were decreased significantly ;protein expressions of Nrf 2,NQO1 and HO -1 2018D01C169) were significantly down -regulated(P<0.01),while the protein expression of Keap 1 was up -regulated significantly (P<0.01). Compared with model group , the apoptotic rate and the content of MDA were decreased significantly in administration groups(P<0.01);the content of GSH in administration groups and the activity of SOD in purified product of phenolic acids group,protocatechuic aldehyde group and rosmarinic acid group were increased significantly (P<0.01). The protein expressions of Nrf2,HO-1 and NQO 1 in purified product of phenolic acids group as well as the protein expression of Nrf 2 in rosmarinic acid group were up -regulated significantly (P<0.01),while the protein expression of Keap 1 was down -regulated significantly in purified product of phenolic acids group and rosmarinic acid group (P<0.01). CONCLUSIONS The phenolic acids components from S. deserta Schang can relieve oxidative stress injury of renal tubular epithelial cells induced by high glucose and high fat ,the mechanism of which may be associated with activating Keap 1/Nrf2 signaling pathway and inhibiting oxidative stress response .
期刊: 2022年第33卷第19期
作者: 王晓梅,任春晖,王新玲,米仁沙·牙库甫,胡君萍
AUTHORS:
关键字: 新疆鼠尾草;酚酸类成分;人肾小管上皮细胞HK-2;氧化损伤;Kelch样ECH相关蛋白1;核转录因子E2相关因子2
KEYWORDS: Salvia deserta Schang;phenolic acid ;human renal tubular epithelial cells HK -2;oxidative injury ;Kelch-like
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