[1]张艳霞,毕智敏,文茜,等.冬凌草甲素调控Nrf2/HO1通路对高糖诱导的肾小管上皮细胞焦亡的影响[J].医学研究与战创伤救治(原医学研究生学报),2026,39(01):24-31.[doi:10.16571/j.cnki.2097-2768.2026.01.004]
　ZHANG Yanxia,BI Zhimin,WEN Qian,et al.Effect of oridonin on high glucose induced pyroptosis of renal tubular epithelial cells by regulating the Nrf2/HO1 pathway[J].JOURNAL OF MEDICALRESEARCH —COMBAT TRAUMA CARE,2026,39(01):24-31.[doi:10.16571/j.cnki.2097-2768.2026.01.004]
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冬凌草甲素调控Nrf2/HO1通路对高糖诱导的肾小管上皮细胞焦亡的影响()

《医学研究与战创伤救治》（原医学研究生学报）[ISSN:1672-271X/CN:32-1713/R]

卷:
第39卷
期数:
2026年01期
页码:
24-31
栏目:
基础研究
出版日期:
2026-01-20

文章信息/Info

Title:
Effect of oridonin on high glucose induced pyroptosis of renal tubular epithelial cells by regulating the Nrf2/HO1 pathway
作者:
张艳霞; 毕智敏; 文茜; 姜倩倩; 林莉; 伍军
武汉市第三医院肾内科，湖北武汉 430000
Author(s):
ZHANG Yanxia;  BI Zhimin;  WEN Qian;  JIANG Qianqian;  LIN Li;  WU Jun
（Department of Nephrology, Wuhan Third Hospital, Wuhan 430000, Hubei, China）
关键词:
冬凌草甲素; 核因子红系2相关因子2/血红素加氧酶1通路; 高糖诱导; 肾小管上皮细胞; 焦亡
Keywords:
oridonin;  nuclear factor erythroid 2 related factor 2/heme oxygenase 1 pathway;  high glucose induction;  renal tubular epithelial cells;  pyroptosis
分类号:
R587.1
DOI:
10.16571/j.cnki.2097-2768.2026.01.004
文献标志码:
A
摘要:
目的探讨冬凌草甲素（Ori）调节核因子红系2相关因子2（Nrf2）/血红素加氧酶1（HO1）通路对高糖（HG）诱导的大鼠肾小管上皮细胞焦亡的影响。方法CCK8法检测不同浓度（2.5、5、10 μmol/L）Ori对HG诱导的NRK52E细胞存活率的影响及给予NRK52E不同干预时间条件下NRK52E细胞的存活率，筛选Ori的作用浓度及时间。将NRK52E细胞分为对照组(Control组，5.6 mmol/L D葡萄糖）、HG组（30 mmol/L D葡萄糖）、HG+Ori组（30 mmol/L D葡萄糖+5 μmol/L Ori）、HG+Ori+siNC组（30 mmol/L D葡萄糖+5 μmol/L Ori+转染siNC）、HG+Ori+siNrf2组（30 mmol/L D葡萄糖+5 μmol/L Ori+转染siNrf2）。透射电镜观察细胞形态；caspase1和PI双染检测细胞焦亡水平；流式细胞术测定细胞中ROS、mtROS水平；乳酸脱氢酶（LDH）试剂盒检测细胞上清中LDH水平；ELISA实验检测细胞上清中IL1β和IL18水平；细胞超氧化物歧化酶（SOD）活性检测试剂盒检测细胞中SOD水平；Western blot实验检测细胞中Nrf2、HO1、NQO1、核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)、GSDMDN、caspase1 p20、白细胞介素1β（IL1β）、IL18蛋白表达。结果与Control组相比，HG组NRK52E细胞肿胀甚至破裂，且细胞膜出现微孔，细胞焦亡率、ROS和mtROS重叠率、LDH、IL1β和IL18水平及NLRP3、GSDMDN、caspase1 p20、IL1β、IL18蛋白表达显著升高（P<0.05），SOD、Nrf2、HO1和NQO1水平显著降低（P<0.05）；与HG组相比，HG+Ori组肿胀、破裂细胞减少，细胞焦亡率、ROS和mtROS重叠率、LDH、IL1β和IL18水平及NLRP3、GSDMDN、caspase1 p20、IL1β、IL18蛋白表达显著降低（P<0.05），SOD、Nrf2、HO1和NQO1水平显著升高（P<0.05）；与HG+Ori+siNC组相比，HG+Ori+siNrf2组肿胀、破裂细胞增多，细胞焦亡率、ROS和mtROS重叠率、LDH、IL1β和IL18水平及NLRP3、GSDMDN、caspase1 p20、IL1β、IL18蛋白表达显著升高（P<0.05），SOD、Nrf2、HO1和NQO1水平显著降低（P<0.05）。结论Ori可能通过调控Nrf2/HO1通路中关键蛋白的表达，抑制HG诱导的肾小管上皮细胞焦亡。
Abstract:
ObjectiveTo investigate the effect of oridonin (Ori) on high glucose (HG)induced pyroptosis in rat renal tubular epithelial cells by regulating the nuclear factor erythroid 2related factor 2 (Nrf2)/heme oxygenase1 (HO1) pathway.MethodsThe Cell Counting Kit8 (CCK8) assay was used to detect the effect of different concentrations (2.5, 5, 10μmol/L) of Ori on the survival rate of HGinduced NRK52E cells and the survival rate of NRK52E cells under different intervention times. The concentration and time of Ori′s action were screened. NRK52E cells were divided into the control group (Control group, 5.6 mmol/L Dglucose), HG group (30 mmol/L Dglucose), HG + Ori group (30 mmol/L Dglucose + 5 μmol/L Ori), HG + Ori + siNC group (30 mmol/L Dglucose + 5 μmol/L Ori + transfection of siNC), and HG + Ori + siNrf2 group (30 mmol/L Dglucose + 5 μmol/L Ori + transfection of siNrf2). The cell morphology was observed by transmission electron microscopy; the level of pyroptosis was detected by caspase1 and PI double staining; the levels of ROS and mtROS in cells were determined by flow cytometry; LDH kit was used to detect the level of LDH in cell supernatant; ELISA was used to detect the levels of IL1βand IL18 in cell supernatant; SOD activity detection kit was used to detect the activity of SOD in cells; Western blot was used to detect the expressions of Nrf2, HO1, NQO1, nucleotidebinding oligomerization domainlike receptor protein 3 (NLRP3), GSDMDN, caspase1 p20, interleukin1β (IL1β), and IL18 proteins.ResultsCompared with the Control group, the cells in the HG group were swollen and even ruptured, and the cell membrane had micropores. The cell pyroptosis rate, the colocalization rate of ROS and mtROS, the levels of LDH, IL1β and IL18, and the expressions of NLRP3, GSDMDN, caspase1 p20, IL1β, and IL18 proteins were significantly increased (P<0.05), while the levels of SOD, Nrf2, HO1, and NQO1 were significantly decreased (P<0.05); compared with the HG group, the cells in the HG + Ori group had less swelling and rupture, and the cell pyroptosis rate, the colocalization rate of ROS and mtROS, the levels of LDH, IL1β and IL18, and the expressions of NLRP3, GSDMDN, caspase1 p20, IL1β, and IL18 proteins were significantly decreased (P<0.05), while the levels of SOD, Nrf2, HO1, and NQO1 were significantly increased (P<0.05); compared with the HG + Ori + siNC group, the cells in the HG + Ori + siNrf2 group had more swelling and rupture, and the cell pyroptosis rate, the colocalization rate of ROS and mtROS, the levels of LDH, IL1β and IL18, and the expressions of NLRP3, GSDMDN, caspase1 p20, IL1β, and IL18 proteins were significantly increased (P<0.05), while the levels of SOD, Nrf2, HO1, and NQO1 were significantly decreased (P<0.05).ConclusionOri may inhibit HGinduced pyroptosis of renal tubular epithelial cells by regulating the expression of key proteins in the Nrf2/HO1 pathway.

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备注/Memo

备注/Memo:
基金项目：武汉市中医药科研项目(WZ24B80)
更新日期/Last Update: 2026-01-20