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  

Study on protective effect and mechanism of phenolic acid components from Salvia deserta Schang on oxidative injury of HK-2 cells

作　　者：王晓梅[1] 任春晖 王新玲[1] 米仁沙·牙库甫[1] 胡君萍[1] WANG Xiaomei;REN Chunhui;WANG Xinling;Mirensha·Yakufu;HU Junping(College of Pharmacy,Xinjiang Medical University,Urumqi 830017,China;Dept.of Pharmacy,Yili Prefecture Youyi Hospital of Xinjiang,Xinjiang Yining 835099,China)

机构地区：[1]新疆医科大学药学院,乌鲁木齐830017 [2]新疆伊犁州友谊医院药剂科,新疆伊宁835099

出　　处：《中国药房》2022年第19期2348-2353,共6页China Pharmacy

基　　金：新疆维吾尔自治区自然科学基金资助项目(No.2018D01C169)。

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+30 mmol/L葡萄糖处理48 h)并加药培养48 h。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。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(P<0.01);protein expressions of Nrf2,NQO1 and HO-1 were significantly down-regulated(P<0.01),while the protein expression of Keap1 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 NQO1 in purified product of phenolic acids group as well as the protein expression of Nrf2 in rosmarinic acid group were

关 键 词：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 

分 类 号：R965[医药卫生—药理学]