大黄素改善高糖条件中人肾小球血管内皮细胞炎症、氧化应激及凋亡作用的研究  

Effect of emodin on improving the inflammation,oxidative stress and apoptosis of human glomerular endothelial cells in high glucose conditions

作　　者：王延海[1] 张雷明[1] 冯艳艳[1] WANG Yan-hai;ZHANG Lei-ming;FENG Yan-yan(Department of Blood Purification,The First Affiliated Hospital of Nanyang Medical College,Nanyang 473058,Henan Province,China)

机构地区：[1]南阳医学高等专科学校第一附属医院血液净化科,河南南阳473058

出　　处：《中国临床药理学杂志》2023年第10期1422-1426,共5页The Chinese Journal of Clinical Pharmacology

基　　金：河南省医学科技攻关联合共建基金资助项目(LHGJ20210982)。

摘　　要：目的研究大黄素对高糖条件中的人肾小球血管内皮细胞(HRGEC)炎症、凋亡和氧化应激水平的影响及其可能的作用机制。方法将体外培养的HRGEC随机分为对照组、模型组和低、中、高浓度实验组。对照组给予5 mmol·L^(-1)葡萄糖处置;模型组给予30 mmol·L^(-1)葡萄糖处置;低、中、高浓度实验组分别给予30 mmol·L^(-1)葡萄糖+5、10、20μmol·L^(-1)大黄素处置。用CCK-8法检测细胞存活率,用试剂盒检测氧化应激指标和炎症因子的水平,用蛋白质印迹法检测凋亡及相关通路蛋白的表达水平。结果中、高浓度实验组和模型组、对照组的HRGEC存活率分别为(83.47±1.71)%、(95.61±2.18)%、(65.83±1.82)%和(100.00±2.34)%,丙二醛分别为(8.54±0.96)、(5.84±0.67)、(15.58±1.67)和(4.32±0.84)μmol·g^(-1),活性氧分别为(30.39±3.43)、(24.64±2.15)、(58.48±4.47)和(18.76±2.12)μmol·g^(-1),白细胞介素-1β分别为(36.47±1.28)、(30.92±1.61)、(49.81±2.31)和(28.73±1.62)pg·mL^(-1),肿瘤坏死因子-α分别为(37.14±2.42)、(26.73±1.54)、(55.41±3.72)和(22.73±2.11)pg·mL^(-1),血红素加氧酶1蛋白相对表达水平分别为0.41±0.09、0.19±0.02、0.98±0.12和0.54±0.12,核因子E2相关因子2蛋白相对表达水平分别为0.21±0.03、0.05±0.01、0.93±0.11和0.41±0.02。中、高浓度实验组的上述指标与模型组比较,差异均有统计学意义(均P<0.05)。结论大黄素能改善高糖条件下HRGEC的存活率,抑制高糖诱导的细胞凋亡及炎症反应,其可能通过抑制Nrf2/HO-1信号通路进而减轻高糖诱导的氧化应激反应。Objective To investigate the effects of emodin on the levels of inflammation,apoptosis and oxidative stress in human glomerular endothelial cells(HRGEC)under high glucose conditions and its possible mechanisms.Methods HRGEC cultured in vitro were randomly divided into control group,model group and experimental-L,-M,-H groups.The control group was treated with 5 mmol·L^(-1)glucose.The model group was treated with 30 mmol·L^(-1)glucose.The experimental-L,-M,-H groups were given 30 mmol·L^(-1)glucose+5,10,20μmol·L^(-1)emodin treatment.The cell survival rate was measured by CCK-8 method.The levels of oxidative stress indicators and inflammatory factors were detected with kit.The expression levels of apoptosis and related pathway protein were measured by Western blot.Results The survival rates of HRGEC in experimental-M,-H groups,model group and control group were(83.47±1.71)%,(95.61±2.18)%,(65.83±1.84)%and(100.00±2.34)%;the malondialdehyde levels were(8.54±0.96),(5.84±0.67),(15.58±1.67)and(4.32±0.84)μmol·g-1;the reactive oxygen species levels were(30.39±3.43),(24.64±2.15),(58.48±4.47)and(18.76±2.12)μmol·g-1;interleukin-1βwere(36.47±1.28),(30.92±1.61),(49.81±2.31)and(28.73±1.62)pg·mL^(-1);tumor necrosis factor-αwere(37.14±2.42),(26.73±1.54),(55.41±3.72)and(22.73±2.11)pg·mL^(-1);the relative expression levels of recombinant heme oxygenase 1 protein were 0.41±0.09,0.19±0.02,0.98±0.12 and 0.54±0.12;the relative expression levels of nuclear factor erythroid 2-related factor 2 protein were 0.21±0.03,0.05±0.01,0.93±0.11 and 0.41±0.02,respectively.The differences of above indexes were statistically significant between the experimental-M,-H groups and the model group(all P<0.05).Conclusion Emodin can improve the survival rate of HRGEC under high glucose conditions in a concentration dependent manner,inhibit apoptosis and inflammatory response induced by high glucose,and inhibit Nrf2/HO-1 signaling pathway to reduce oxidative stress response induced by high glucose.

关 键 词：大黄素 糖尿病肾病 细胞凋亡 氧化应激 炎症反应 

分 类 号：R28[医药卫生—中药学]