黄芪皂苷Ⅰ通过抑制足细胞焦亡干预糖尿病肾脏疾病的机制研究

段亚飞; 石贤聪; 赵靓; 吕明真; 任心棋; 古豫蕾; 徐江雁; 张振强; 苗晋鑫; 谢治深; 张效威

doi:10.3969/j.issn.1006-2157.2024.10.011

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黄芪皂苷Ⅰ通过抑制足细胞焦亡干预糖尿病肾脏疾病的机制研究

实验研究 | 更新时间：2024-10-29

- 黄芪皂苷Ⅰ通过抑制足细胞焦亡干预糖尿病肾脏疾病的机制研究
- Study on the mechanism of astragaloside Ⅰ inhibiting podocyte pyroptosis in diabetic kidney disease
- 北京中医药大学学报 2024年47卷第10期页码：1408-1415
- 作者机构：
  
  1.河南中医药大学中医药科学院　郑州　450046
  2.河南中医药大学豫药全产业链研发河南省协同创新中心
  3.河南中医药大学中医学院
- 作者简介：
  
  段亚飞，女，在读硕士生
  #张效威，男，博士，助理研究员，硕士生导师，主要研究方向：代谢性疾病及靶器官损伤的中药活性成分发现及作用机制，E-mail：zhangxw2020@163.com
- 基金信息：
  
  国家重点研发计划项目(2020YFE0201800);国家自然科学基金项目(82104471);河南省重点研发专项(221111520300);河南省省级科技研发计划联合基金(232301420093);河南省高校科技创新人才支持计划(24HASTIT072);国家中医药管理局国际合作司中医药国际合作专项（基地类项目）(0730-236132ZC0054/01-05)
- DOI：10.3969/j.issn.1006-2157.2024.10.011
  中图分类号： R285.5
- 收稿日期：2024-06-24，
  
  网络出版日期：2024-08-20，
  
  纸质出版日期：2024-10-30
- 稿件说明：
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段亚飞, 石贤聪, 赵靓, 等. 黄芪皂苷Ⅰ通过抑制足细胞焦亡干预糖尿病肾脏疾病的机制研究[J]. 北京中医药大学学报, 2024,47(10):1408-1415.

DUAN Yafei, SHI Xiancong, ZHAO Liang, et al. Study on the mechanism of astragaloside Ⅰ inhibiting podocyte pyroptosis in diabetic kidney disease[J]. Journal of beijing university of traditional chinese medicine, 2024, 47(10): 1408-1415.
段亚飞, 石贤聪, 赵靓, 等. 黄芪皂苷Ⅰ通过抑制足细胞焦亡干预糖尿病肾脏疾病的机制研究[J]. 北京中医药大学学报, 2024,47(10):1408-1415. DOI： 10.3969/j.issn.1006-2157.2024.10.011.

DUAN Yafei, SHI Xiancong, ZHAO Liang, et al. Study on the mechanism of astragaloside Ⅰ inhibiting podocyte pyroptosis in diabetic kidney disease[J]. Journal of beijing university of traditional chinese medicine, 2024, 47(10): 1408-1415. DOI： 10.3969/j.issn.1006-2157.2024.10.011.

摘要

目的

探讨黄芪活性成分黄芪皂苷Ⅰ抑制足细胞损伤、改善糖尿病肾脏疾病的作用机制。

方法

60只雄性db/db小鼠按体质量随机分为模型组、黄芪皂苷Ⅰ低剂量组(10 mg/kg)、黄芪皂苷Ⅰ中剂量组(20 mg/kg)、黄芪皂苷Ⅰ高剂量组(40 mg/kg)及缬沙坦组(10 mg/kg)，每组12只；12只db/db同窝对照db/m小鼠作为对照组。灌胃给药8周。透射电子显微镜观察肾脏超微结构；免疫组织化学法、蛋白质印迹法检测肾脏足细胞标志物肾病蛋白(nephrin)的表达情况；酶联免疫吸附测定法检测小鼠血清白细胞介素-1β(IL-1β)、白细胞介素-18(IL-18)含量；蛋白质印迹法检测肾脏组织NOD样受体热蛋白结构域相关蛋白3(NLRP3)、胱天蛋白酶-1(Caspase-1)、消皮素D(GSDMD)蛋白表达。

结果

与对照组比较，模型组小鼠肾小球出现明显的足细胞丢失、足突融合等现象；肾脏nephrin蛋白表达下降(

0.05)；血清IL-1β、IL-18含量升高(均

0.05)；NLRP3、裂解型Caspase-1(Cleaved-Caspase-1)、GSDMD-N蛋白表达升高(均

0.05)。与模型组比较，黄芪皂苷Ⅰ给药组肾脏病理损伤得到缓解；Nephein蛋白表达升高(

0.05)；血清IL-1β、IL-18含量下降(均

0.05)；NLRP3、Cleaved-Caspase-1、GSDMD-N蛋白表达下降(均

0.05)。

结论

黄芪皂苷I可能通过抑制细胞焦亡、改善足细胞损伤发挥干预糖尿病肾脏疾病的作用。

Abstract

Objective

To investigate the mechanism of astragaloside I

the active constituent of milkvetch root

in inhibiting podocyte injury and improving diabetic kidney disease.

Methods

According to the body weight

60 male db/db mice were randomly divided into the model group

astragaloside Ⅰ low-dose group (10 mg/kg)

astragaloside I medium-dose group (20 mg/kg)

astragaloside I high-dose group (40 mg/kg)

and valsartan group (10 mg/kg)

with 12 mice per group. Twelve db/db littermate control db/m mice were used as the control group. The drug was administered by gavage for 8 weeks. Transmission electron microscope was used to observe the ultrastructure of the kidney; immunohistochemistry and Western blotting were used to detect the expression of nephrotic protein (nephrin)

a marker of renal podocytes; enzyme-linked immunosorbent assay was used to detect the contents of interleukin-1β (IL-1β) and interleukin-18 (IL-18) in the serum of mice; Western blotting was used to detect the protein expressions of NOD-like receptor thermoprotein domain-related protein 3 (NLRP3)

cysteinyl aspartate specific proteinase 1 (Caspase-1)

and Gasdermin D (GSDMD) in kidney tissue.

Results

Compared with the control group

the glomeruli of the model group showed obvious podocyte loss and foot process fusion; the protein expression of nephrin was decreased (

0.05); the contents of IL-1β and IL-18 in serum were increased (

0.05); the protein expressions of NLRP3

Cleaved-Caspase-1

and GSDMD-N were increased (

0.05). Compared with the model group

the renal pathological damage in the astragaloside Ⅰ administration groups were alleviated; the protein expression of nephrin was increased (

0.05); the contents of IL-1β and IL-18 in serum were decreased (

0.05); the protein expressions of NLRP3

Cleaved-Caspase-1

and GSDMD-N were decreased (

0.05).

Conclusion

Astragaloside I may play a role in intervening diabetic kidney disease by inhibiting pyroptosis and improving podocyte injury.

关键词

Keywords

references

AFKARIAN M , ZELNICK LR , HALL YN , et al . Clinical manifestations of kidney disease among US adults with diabetes, 1988-2014 [J ] . JAMA , 2016 , 316 ( 6 ): 602 - 610 .

DE BOER IH , RUE TC , HALL YN , et al . Temporal trends in the prevalence of diabetic kidney disease in the United States [J ] . JAMA , 2011 , 305 ( 24 ): 2532 - 2539 .

RUIZ-ORTEGA M , RODRIGUES-DIEZ RR , LAVOZ C , et al . Special issue ”diabetic nephropathy: diagnosis, prevention and treatment” [J ] . J Clin Med , 2020 , 9 ( 3 ): 813 .

FITCHETT D . A safety update on sodium glucose co-transporter 2 inhibitors [J ] . Diabetes Obes Metab , 2019 , 21 ( Suppl 2 ): 34 - 42 .

LI GR , LIU C , YANG L , et al . Syringaresinol protects against diabetic nephropathy by inhibiting pyroptosis via NRF2-mediated antioxidant pathway [J ] . Cell Biol Toxicol , 2023 , 39 ( 3 ): 621 - 639 .

LI XH , DONG X , ZHANG LY , et al . Astragaloside Ⅳ attenuates renal tubule injury in DKD rats via suppression of CD36-mediated NLRP3 inflammasome activation [J ] . Front Pharmacol , 2024 , 15 : 1285797 .

LIU YH , HE MY , XIONG H , et al . Induction of pyroptosis in renal tubular epithelial cells using high glucose [J ] . Front Med , 2022 , 9 : 874916 .

ZUO Y , CHEN L , GU HP , et al . GSDMD-mediated pyroptosis: a critical mechanism of diabetic nephropathy [J ] . Expert Rev Mol Med , 2021 , 23 : e23 .

ZHANG XW , ZHAO L , XIANG SX , et al . Yishen Tongluo formula alleviates diabetic kidney disease through regulating Sirt6/TGF-β1/Smad2/3 pathway and promoting degradation of TGF-β1 [J ] . J Ethnopharmacol , 2023 , 307 : 116243 .

SHI Y , SHI XJ , ZHAO MM , et al . Pharmacological potential of Astragali Radix for the treatment of kidney diseases [J ] . Phytomedicine , 2024 , 123 : 155196 .

ZHANG YY , TAN RZ , ZHANG XQ , et al . Calycosin ameliorates diabetes-induced renal inflammation via the NF-κB pathway in vitro and in vivo [J ] . Med Sci Monit , 2019 , 25 : 1671 - 1678 .

HE KQ , LI WZ , CHAI XQ , et al . Astragaloside Ⅳ prevents kidney injury caused by iatrogenic hyperinsulinemia in a streptozotocin-induced diabetic rat model [J ] . Int J Mol Med , 2018 , 41 ( 2 ): 1078 - 1088 .

张蕾，刘旭生 . 糖尿病肾病中医病名源流探索性研究 [J ] . 辽宁中医杂志， 2012 , 39 ( 1 ): 52 - 54 .

师卿杰，李明晓，李郑生 . 国医大师李振华从虚、浊、瘀、毒、衰论治慢性肾功能衰竭经验介绍 [J ] . 新中医， 2022 , 54 ( 24 ): 197 - 201 .

ZHENG YJ , REN WY , ZHANG LN , et al . A review of the pharmacological action of Astragalus polysaccharide [J ] . Front Pharmacol , 2020 , 11 : 349 .

WANG Y , LIU X , HU TD , et al . Astragalus saponins improves stroke by promoting the proliferation of neural stem cells through phosphorylation of Akt [J ] . J Ethnopharmacol , 2021 , 277 : 114224 .

NALBANTSOY A , NESIL T , YILMAZ-DILSIZ O , et al . Evaluation of the immunomodulatory properties in mice and in vitro anti-inflammatory activity of cycloartane type saponins from Astragalus species [J ] . J Ethnopharmacol , 2012 , 139 ( 2 ): 574 - 581 .

HINKOV A , TSVETKOV V , SHKONDROV A , et al . Effect of a total extract and saponins from Astragalus glycyphyllos L. on human coronavirus replication in vitro [J ] . Int J Mol Sci , 2023 , 24 ( 22 ): 16525 .

WELSH GI , SALEEM MA . Nephrin-signature molecule of the glomerular podocyte [J ] . J Pathol , 2010 , 220 ( 3 ): 328 - 337 .

LI XZ , HE JC . An update: the role of Nephrin inside and outside the kidney [J ] . Sci China Life Sci , 2015 ， 58 ( 7 ): 649 - 657 .

卿山林，骆强，任波，等 . 高剂量缬沙坦对老年糖尿病肾病伴高血压患者血压及心肾功能的影响 [J ] . 成都医学院学报， 2020 , 15 ( 2 ): 247 - 250 .

DAVIS BJ , CAO ZM , DE GASPARO M , et al . Disparate effects of angiotensin Ⅱ antagonists and calcium channel blockers on albuminuria in experimental diabetes and hypertension: potential role of nephrin [J ] . J Hypertens , 2003 , 21 ( 1 ): 209 - 216 .

THOMAS MC , BROWNLEE M , SUSZTAK K , et al . Diabetic kidney disease [J ] . Nat Rev Dis Primers , 2015 , 1 ( 1 ): 15018 .

JIN Q , LIU TT , QIAO Y , et al . Oxidative stress and inflammation in diabetic nephropathy: role of polyphenols [J ] . Front Immunol , 2023 , 14 : 1185317 .

JUN WD , MAKINO H . Inflammation and the pathogenesis of diabetic nephropathy [J ] . Clin Sci , 2013 ， 124 ( 3 ): 139 - 152 .

ADAMOPOULOS C , MIHAILIDOU C , GRIVAKI C , et al . Systemic effects of AGEs in ER stress induction in vivo [J ] . Glycoconj J , 2016 , 33 ( 4 ): 537 - 544 .

KUMAR V , SINGHAL PC . APOL1 and kidney cell function [J ] . Am J Physiol Renal Physiol , 2019 , 317 ( 2 ): 463 - 477 .

WANG MZ , WANG J , CAO DW , et al . Fucoidan alleviates renal fibrosis in diabetic kidney disease via inhibition of NLRP3 inflammasome-mediated podocyte pyroptosis [J ] . Front Pharmacol , 2022 , 13 : 790937 .

全力，梁安杰，舒亮辉，等 . 基于数据挖掘分析周恩超教授治疗糖尿病肾病的中药组方规律 [J ] . 基层中医药， 2023 , 2 ( 7 ): 94 - 101 .

周冬祺 . 初步探讨糖肾方干预早期糖尿病肾脏疾病微量白蛋白尿的临床研究 [D ] . 成都：成都中医药大学， 2022 .

徐杰，周霜，谢旦红，等 . 三黄糖肾康颗粒治疗糖尿病肾病患者的疗效观察及对TLR4、NF-κB、MCP-1的影响 [J ] . 中国中医药科技， 2024 , 31 ( 3 ): 440 - 442 .

CHEN YF , GUI DK , CHEN JG , et al . Down-regulation of PERK-ATF4-CHOP pathway by Astragaloside Ⅳ is associated with the inhibition of endoplasmic reticulum stress-induced podocyte apoptosis in diabetic rats [J ] . Cell Physiol Biochem , 2014 , 33 ( 6 ): 1975 - 1987 .

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