Effects of <italic style="font-style: italic">Danggui Shaoyao Powder</italic> （当归芍药散） on Lipotoxic Injury in Hypoxia and High Glucose-Induced Glomerular Endothelial Cells

LI Ruijia; ZHANG Qianqian; LI Jing; WANG Zixuan; GUO Shilong; DONG Wen; GUO Dengzhou

doi:10.13288/j.11-2166/r.2025.21.012

您当前的位置：

首页 >

文章列表页 >

Effects of Danggui Shaoyao Powder （当归芍药散） on Lipotoxic Injury in Hypoxia and High Glucose-Induced Glomerular Endothelial Cells

更新时间：2025-10-31

- Effects of Danggui Shaoyao Powder （当归芍药散） on Lipotoxic Injury in Hypoxia and High Glucose-Induced Glomerular Endothelial Cells
- Journal of Traditional Chinese Medicine Vol. 66, Issue 21, Pages: 2249-2258(2025)
- 作者机构：
  
  1.河北中医药大学研究生院，河北省石家庄市桥西区新石南路326号，050200
  2.河北省中医院
  3.河北医科大学第一医院
- 作者简介：
- 基金信息：
- DOI：10.13288/j.11-2166/r.2025.21.012
  CLC：
- Received：10 June 2025，
  
  Revised：2025-07-10，
  
  Published：02 November 2025
- 稿件说明：
移动端阅览
李睿嘉,张倩倩,李静等.当归芍药散对缺氧高糖诱导肾小球内皮细胞脂毒性损伤的影响[J].中医杂志,2025,66(21):2249-2258.

LI Ruijia,ZHANG Qianqian,LI Jing,et al.Effects of Danggui Shaoyao Powder （当归芍药散） on Lipotoxic Injury in Hypoxia and High Glucose-Induced Glomerular Endothelial Cells[J].Journal of Traditional Chinese Medicine,2025,66(21):2249-2258.
李睿嘉,张倩倩,李静等.当归芍药散对缺氧高糖诱导肾小球内皮细胞脂毒性损伤的影响[J].中医杂志,2025,66(21):2249-2258. DOI： 10.13288/j.11-2166/r.2025.21.012.

LI Ruijia,ZHANG Qianqian,LI Jing,et al.Effects of Danggui Shaoyao Powder （当归芍药散） on Lipotoxic Injury in Hypoxia and High Glucose-Induced Glomerular Endothelial Cells[J].Journal of Traditional Chinese Medicine,2025,66(21):2249-2258. DOI： 10.13288/j.11-2166/r.2025.21.012.

摘要

目的

基于抑制沉默信息调节因子1（Sirt1）调控缺氧诱导因子1α（Hif-1α）/内质网应激（ERS）轴探讨当归芍药散治疗糖尿病肾脏疾病（DKD）的可能作用机制。

方法

通过CCK8法检测小鼠肾小球内皮细胞（MRGEC）在不同浓度当归芍药散干预下的增殖率，筛选当归芍药散干预浓度进行后续实验。将MRGEC分为缺氧低糖对照组、缺氧高糖模型组、当归芍药散组、厄贝沙坦组、Sirt1抑制剂组、Sirt1抑制剂+当归芍药散组、ERS抑制剂组，按照分组分别予对应处理。观察细胞形态，采用流式细胞术检测细胞凋亡率、细胞内活性氧（ROS）水平，全自动生化仪检测细胞中甘油三酯（TG）和总胆固醇（TC）水平，Western Blot法检测

细胞中Sirt1、Hif-1α、B细胞淋巴瘤2（BCL-2）、磷酸化的蛋白激酶R样内质网激酶（p-PERK）、葡萄糖调节蛋白78（GRP78）、激活转录因子4（ATF4）、C/EBP同源蛋白（CHOP）、分化簇31（CD31）、低密度脂蛋白受体（VLDLr）蛋白水平，RT-qPCR法检测细胞中

GRP78、ATF4、CHOP

mRNA表达，免疫荧光法检测细胞中Hif-1α、GRP78、ATF4、CHOP的表达。

结果

筛选出0.7 mg/ml浓度的当归芍药散进行后续实验。缺氧低糖对照组MRGEC呈梭形，排列规则且有序；缺氧高糖模型组MRGEC胞体缩小，细胞间隙增大，失去有序排列特征；Sirt1抑制剂组MRGEC杂乱分布，细胞间隙更大；当归芍药散组、厄贝沙坦组、Sirt1抑制剂+当归芍药散组、ERS抑制剂组上述特征均有所缓解。与缺氧低糖对照组比较，缺氧高糖模型组细胞凋亡率、细胞内ROS水平升高（

＜0.05）；细胞中TG、TC水平升高，Sirt1、BCL-2、CD31蛋白水平降低，Hif-1α、p-PERK、VLDLr蛋白水平升高，GRP78、ATF4、CHOP蛋白及mRNA表达升高（

＜0.05）。与缺氧高糖模型组比较，Sirt1抑制剂组上述指标更加严重，当归芍药散组、厄贝沙坦组、ERS抑制剂组上述指标有所改善（

＜0.05）。与Sirt1抑制剂+当归芍药散组比较，当归芍药散组细胞上述指标有所改善（

＜0.05）。与Sirt1抑制剂组比较，Sirt1抑制剂+当归芍药散组细胞上述指标有所改善（

＜0.05）。

结论

当归芍药散可以抑制缺氧高糖诱导的MRGEC凋亡，其可能通过靶向Sirt1调控Hif-1α/ERS，从而缓解MRGEC的脂毒性损伤，延缓DKD的进展。

Abstract

Objective

To investigate the potential mechanism of

Danggui Shaoyao Powder

（当归芍药散， DSP） in the treatment of diabetic kidney disease （DKD） based on the regulatory role of silent information regulator 1 （Sirt1） on hypoxia-inducible factor 1α （Hif-1α） and endoplasmic reticulum stress （ERS）.

Methods

The proliferation rate of mouse glomerular endothelial cells （MRGECs） under different concentrations of DSP was measured using the CCK-8 assay to determine the optimal intervention concentration for subsequent experiments. MRGECs were divided into the following groups： hypoxia-low glucose control， hypoxia-high glucose model， DSP， irbesartan， Sirt1 inhibitor， Sirt1 inhibitor + DSP， and ERS inhibitor. Cells in each group received corresponding treatments. Morphological changes were observed microscopically. Apoptosis rate and intracellular reactive oxygen species （ROS） levels were measured by flow cytometry； intracellular triglyceride （TG） and total cholesterol （TC） levels were assessed using an automated biochemical analyzer. Western Blotting was performed to detect protein levels of Sirt1， Hif-1α， B-cell lymphoma 2 （BCL-2）， phosphorylated protein kinase R-like endoplasmic reticulum kinase （p-PERK）， glucose-regulated protein 78 （GRP78）， activating transcription factor 4 （ATF4）， C/EBP homologous protein （CHOP）， cluster of differentiation 31 （CD31）， and very low-density lipoprotein receptor （VLDLr）. mRNA expression of GRP78， ATF4， and CHOP was determined by RT-qPCR， and the expression of Hif-1α， GRP78， ATF4， and CHOP was visualized by immunofluorescence.

Results

The optimal DSP concentration was determined to be 0.7 mg/ml. In the hypoxia-low glucose control group， MRGECs showed spindle-like morphology and regular alignment. In contrast， the hypoxia-high glucose model group exhibited cell shrinkage， widened intercellular spaces， and disordered arrangement. Cells in the Sirt1 inhibitor group displayed more severe disorganization， while these morphological alterations were alleviated in the DSP， irbesartan， Sirt1 inhibitor + DSP， and ERS inhibitor groups. Compared with the hypoxia-low glucose control group， the hypoxia-high glucose model group showed significantly increased apoptosis rate and intracellular ROS levels （

＜0.05）， elevated TG and TC levels， decreased Sirt1， BCL-2， and CD31 protein expression， increased Hif-1α， p-PERK， and VLDLr protein levels， and upregulated GRP78， ATF4， and CHOP protein and mRNA expression （

＜0.05）. Compared with the hypoxia-high glucose model group， these changes were further aggravated in the Sirt1 inhibitor group but significantly improved in the DSP， irbesartan， and ERS inhibitor groups （

＜0.05）. Compared with the Sirt1 inhibitor + DSP group， the DSP group showed better improvements in all the above indices （

＜0.05）. Compared with the Sirt1 inhibitor group， the Sirt1 inhibitor + DSP group also exhibited significant amelioration in these parameters （

＜0.0

5）.

Conclusion

DSP inhibits apoptosis of MRGECs induced by hypoxia and high glucose， possibly by targeting Sirt1 to regulate the Hif-1α/ERS axis， thereby alleviating lipotoxic injury and delaying the progression of DKD.

关键词

Keywords

references

SHEN S ， ZHONG H ， ZHOU X ， et al . Advances in traditional Chinese medicine research in diabetic kidney disease treatment ［J］. Pharm Biol ， 2024 ， 62 （ 1 ）： 222 - 232 .

LIU XJ ， HU XK ， YANG H ， et al . A review of traditional Chinese medicine on treatment of diabetic nephropathy and the involved mechanisms ［J］. Am J Chin Med ， 2022 ， 50 （ 7 ）： 1739 - 1779 .

WANG MJ ， CAI X ， LIANG RY ， et al . SIRT1-dependent deacetylation of Txnip H3K9ac is critical for exenatide-improved diabetic kidney disease ［J］. Biomed Pharmacother ， 2023 ， 167 ： 115515 . doi： 10.1016/ j. biopha. 2023. 115515 http://dx.doi.org/10.1016/j.biopha.2023.115515 .

MA XJ ， MA JR ， LENG T ， et al . Advances in oxidative stress in pathogenesis of diabetic kidney disease and efficacy of TCM intervention ［J］. Ren Fail ， 2023 ， 45 （ 1 ）： 2146512 .

QIN X ， JIANG M ， ZHAO Y ， et al . Berberine protects against diabetic kidney disease via promoting PGC-1α- regulated mitochondrial energy homeostasis ［J］. Br J Pharmacol ， 2020 ， 177 （ 16 ）： 3646 - 3661 .

孙卫卫，陈荟溪，胡聿昕，等 . 糖尿病肾脏疾病辨治的难点和临床治疗模式［J］. 中医杂志， 2025 ， 66 （ 6 ）： 569 - 574 .

中华中医药学会，北京中医药大学东直门医院，北京中医药大学 . 糖尿病肾脏疾病中西医结合诊疗指南［J］. 北京中医药大学学报， 2024 ， 47 （ 4 ）： 580 - 592 .

徐建龙，禹田，聂莉芳 . 聂莉芳教授运用参芪当归芍药散治疗慢性肾脏病的经验［J］. 中国中西医结合肾病杂志， 2021 ， 22 （ 9 ）： 757 - 758 .

梅莎莎，宋恩峰，项琼 . 当归芍药散联合氯沙坦治疗早期糖尿病肾病临床观察［J］. 辽宁中医药大学学报， 2016 ， 18 （ 2 ）： 101 - 103 .

MOKAS S ， LARIVIÈRE R ， LAMALICE L ， et al . Hypoxia-inducible factor-1 plays a role in phosphate-induced vascular smooth muscle cell calcification ［J］. Kidney Int ， 2016 ， 90 （ 3 ）： 598 - 609 .

LI Y ， LONG WH ， ZHANG HF ， et al . Irbesartan ameliorates diabetic nephropathy by activating the Nrf2/Keap1 pathway and suppressing NLRP3 inflammasomes in vivo and in vitro ［J］. Int Immunopharmacol ， 2024 ， 131 ： 111844 . doi： 10.1016/ j.intimp. 2024.111844 http://dx.doi.org/10.1016/j.intimp.2024.111844 .

SU PP ， LIU DW ， ZHOU SJ ， et al . Down-regulation of Risa improves podocyte injury by enhancing autophagy in diabetic nephropathy ［J］. Mil Med Res ， 2022 ， 9 （ 1 ）： 23 .

ZHANG T ， CHI YQ ， KANG YL ， et al . Resveratrol ameliorates podocyte damage in diabetic mice via SIRT1/PGC-1α mediated attenuation of mitochondrial oxidative stress ［J］. J Cell Physiol ， 2019 ， 234 （ 4 ）： 5033 - 5043 .

MONA P ， ANNA B ， ROSALÍA RR ， et al . SIRT1 regulates hepatic vldlr levels ［J］. Cell Commun Signal ， 2024 ， 22 ： 297 . doi： 10.1186/s12964-024-01666-y http://dx.doi.org/10.1186/s12964-024-01666-y .

CHEN W ， WU P ， YU F ， et al . HIF-1α regulates bone homeostasis and angiogenesis， participating in the occurrence of bone metabolic diseases ［J］. Cells ， 2022 ， 11 （ 22 ）： 3552 .

TANG YY ， WANG DC ， WANG YQ ， et al . Emerging role of hypoxia-inducible factor-1α in inflammatory autoimmune diseases： a comprehensive review ［J］. Front Immunol ， 2023 ， 13 ： 1073971 . doi： 10.3389/ fimmu. 2022. 1073971 http://dx.doi.org/10.3389/fimmu.2022.1073971 .

SHI S ， OU X ， LIU C ， et al . Research progress of HIF-1α on immunotherapy outcomes in immune vascular microenvironment ［J］. Front Immunol ， 2025 ， 16 ： 1549276 . doi： 10.3389/ fimmu. 2025. 1549276 http://dx.doi.org/10.3389/fimmu.2025.1549276 .

LEE SY ， LEE AR ， CHOI JW ， et al . IL-17 induces autophagy dysfunction to promote inflammatory cell death and fibrosis in keloid fibroblasts via the STAT3 and HIF-1α dependent signaling pathways ［J］. Front Immunol ， 2022 ， 13 ： 888719 . doi： 10.3389/ fimmu. 2022. 888719 http://dx.doi.org/10.3389/fimmu.2022.888719 .

RASHID M ， ZADEH LR ， BARADARAN B ， et al . Up-down regulation of HIF-1α in cancer progression ［J］. Gene ， 2021 ， 798 ： 145796 . doi： 10.1016/j.gene.2021. 145796 http://dx.doi.org/10.1016/j.gene.2021.145796 .

SONG CW ， KIM H ， KIM MS ， et al . Role of HIF-1α in the responses of tumors to radiotherapy and chemotherapy ［J］. Cancer Res Treat ， 2025 ， 57 （ 1 ）： 1 - 10 .

ZHANG FJ ， LUO W ， LEI GH . Role of HIF-1α and HIF-2α in osteoarthritis ［J］. Jt Bone Spine ， 2015 ， 82 （ 3 ）： 144 - 147 .

YANG XC ， WANG X ， LUO L ， et al . RNA interference suppression of A100A4 reduces the growth and metastatic phenotype of human renal cancer cells via NF-κB-dependent MMP-2 and bcl-2 pathway ［J］. Eur Rev Med Pharmacol Sci ， 2013 ， 17 （ 12 ）： 1669 - 1680 .

查看原文

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

LIU Guangzhen's Experience in Treating Diabetic Kidney Disease Using the "Four Methods of Unblocking Collaterals"

WANG Yaoxian's Experience in Treating Diabetic Kidney Disease from the Perspective of Spleen and Stomach：Based on the Theory of "Internal Heat Leading to Concretions"

Exploration of the Theory on Etiology and Pathogenesis of Altitude Sickness in Traditional Chinese Medicine：Concurrent Discussion on "Oxygen" as the Seventh Pathogenic Factors

Effects of Modified Shoutai Pill （寿胎丸） on Endoplasmic Reticulum Stress and Decidualization in the Endometrium for Hyperandrogenism and Insulin Resistance-Induced Fetal Loss of Rats with Polycystic Ovary Syndrome

Effects of Bushen Tiaojing Formula （补肾调经方） on Blastocyst Cell Apoptosis and Endoplasmic Reticulum Stress in Repeated Controlled Ovarian Stimulation Model Mice

Related Author

PENG Qianhong

XING Jianyue

刘光珍

ZHANG Bo

HU Yuxin

ZHAO Cong

ZHANG Jiale

JIANG Weimin

Related Institution

Shanxi Provincial Hospital of Traditional Chinese Medicine

Shanxi University of Traditional Chinese Medicine

河南中医药大学

Cangzhou Central Hospital

Beijing University of Chinese Medicine

Address：No.16, Nanxiao street, Dongzhimen, Dongcheng District, Beijing Postal code：100700
Tel：010-64035632 Email：jtcmcn@188.com
Technical support is provided by Beijing Founder electronics co., LTD 京ICP备09064830号-19 京公网安备11010102007558号
It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.

⁰

Effects of Danggui Shaoyao Powder （当归芍药散） on Lipotoxic Injury in Hypoxia and High Glucose-Induced Glomerular Endothelial Cells

DOI：10.13288/j.11-2166/r.2025.21.012

摘要

Abstract

关键词

Keywords

references