Study on protective effect of echinacoside on diabetic rats with renal injury based on sirt1-FOXO1 pathway

Shiyu NIU; Ting YE; Jiayuan YU; Rong FAN

doi:10.16305/j.1007-1334.2021.2004224

您当前的位置：

首页 >

文章列表页 >

Study on protective effect of echinacoside on diabetic rats with renal injury based on sirt1-FOXO1 pathway

更新时间：2022-08-03

- Study on protective effect of echinacoside on diabetic rats with renal injury based on sirt1-FOXO1 pathway
- Shanghai Journal of Traditional Chinese Medicine Vol. 55, Issue 2, Pages: 76-81(2021)
- 作者机构：
  
  1.黑龙江中医药大学附属第二医院内分泌科（黑龙江　哈尔滨　150001）
  2.黑龙江中医药大学附属第二医院检验科（黑龙江　哈尔滨　150001）
- 作者简介：
- 基金信息：
- DOI：10.16305/j.1007-1334.2021.2004224
  CLC：
扫描看全文
Shiyu NIU, Ting YE, Jiayuan YU, et al. Study on protective effect of echinacoside on diabetic rats with renal injury based on sirt1-FOXO1 pathway. [J]. Shanghai Journal of Traditional Chinese Medicine 55(2):76-81(2021)
DOI：

Shiyu NIU, Ting YE, Jiayuan YU, et al. Study on protective effect of echinacoside on diabetic rats with renal injury based on sirt1-FOXO1 pathway. [J]. Shanghai Journal of Traditional Chinese Medicine 55(2):76-81(2021) DOI： 10.16305/j.1007-1334.2021.2004224.

摘要

目的,2,基于沉默信息调节因子1（sirt1）/叉头转录因子1（FOXO1）通路研究松果菊苷对糖尿病肾损伤大鼠的保护作用。,方法,2,建立糖尿病肾损伤大鼠模型，随机分为模型组、松果菊苷组、EX527组（sirt1抑制剂）、松果菊苷-EX527组，每组12只，另取12只SD大鼠设为对照组；分组干预后，采用全自动生化分析仪测定大鼠肾功能指标血清肌酐（Scr）、血尿酸（SUA）、尿微量白蛋白（UMA）水平；采用HE染色检测大鼠肾组织病理形态；采用超氧化物歧化酶（SOD）检测试剂盒及丙二醛（MDA）检测试剂盒分别检测肾组织中SOD、MDA水平；采用酶联免疫吸附试验（ELISA）检测大鼠血清中肿瘤坏死因子-α（TNF-α）、白介素-6（IL-6）水平；采用蛋白免疫印迹法检测各组大鼠肾组织sirt1/FOXO1通路相关蛋白表达。,结果,2,与对照组相比，模型组大鼠肾脏可见肾小球体积增大，系膜基质增多，肾小管肿胀、坏死伴空泡样变性，炎性浸润等病理损伤，肾组织SOD含量、sirt1表达降低（,P,<,0.01），Scr、SUA、UMA、血清TNF-α及IL-6水平、肾组织MDA含量、acely-FOXO1/FOXO1升高（,P,<,0.01）。与模型组相比，松果菊苷组大鼠肾组织病理损伤减轻，肾组织SOD含量、sirt1表达升高（,P,<,0.01），Scr、SUA、UMA、血清TNF-α及IL-6水平、肾组织MDA含量、acely-FOXO1/FOXO1降低（,P,<,0.01）；EX527组大鼠肾组织病理损伤加重，肾组织SOD含量、sirt1表达降低（,P,<,0.01），Scr、SUA、UMA、血清TNF-α及IL-6水平、肾组织MDA含量、acely-FOXO1/FOXO1升高（,P,<,0.01）。与松果菊苷组相比，松果菊苷-EX527组大鼠肾组织病理损伤加重，肾组织SOD含量、sirt1表达降低（,P,<,0.01），Scr、SUA、UMA、血清TNF-α及IL-6水平、肾组织MDA含量、acely-FOXO1/FOXO1升高（,P,<,0.01）。与EX527组比较，松果菊苷-EX527组大鼠肾组织病理损伤减轻，肾组织SOD含量、sirt1表达升高（,P,<,0.01），Scr、SUA、UMA、血清TNF-α及IL-6水平、肾组织MDA含量、acely-FOXO1/FOXO1降低（,P,<,0.01）。,结论,2,松果菊苷可能通过激活sirt1/FOXO1通路，抑制氧化应激及炎症反应发生，减轻糖尿病肾损伤。

Abstract

Objective,2,To study the protective effect of echinacoside on diabetic rats with renal injury by sirt1/FOXO1 pathway.,Methods,2,Diabetic renal injury rats were randomly divided into three groups: model group, echinacoside, EX527, and echinacoside-EX527 with 12 rats in each group. Other 12 SD rats were selected as the control group. Furthermore, serum creatinine (Scr) , serum uric acid (SUA) and urinary microalbumin (UMA) were measured by automatic biochemical analyzer. HE staining was used to detect the pathological morphology of renal tissue. Superoxide dismutase (SOD) test kit and malondialdehyde (MDA) test kit were used to detect the levels of SOD and MDA in renal tissue. The levels of tumornecrosis factor-α (TNF-α) and interleukin-6 (IL-6) in serum of rats were detected by enzyme-linked immunosorbent assay (ELISA) . The expression of sirt1/FOXO1 pathway related protein was detected by Western blot.,Results,2,Compared with the control group, the renal glomerulus volume and mesangial matrix of rats in the model group were increased, and the renal tubules were swollen and necrotic with vacuolized degeneration and inflammatory infiltration. In addition, the content of SOD and the expression of sirt1 in renal tissue decreased (,P,<,0.01) , while Scr, SUA, UMA, levels of serum TNF-α and IL-6, content of MDA in renal tissue and acely FOXO1/FOXO1 were all increased (,P,<,0.01) . Compared with the model group, the pathological damage of renal tissue in the echinacoside group was reduced, and the content of SOD and the expression of sirt1 in renal tissue increased (,P,<,0.01) . Besides, Scr, SUA, UMA, levels of serum TNF-α and IL-6, content of MDA in renal tissue and acely FOXO1/FOXO1 were decreased (,P,<,0.01) . In the EX527 group, the pathological damage of renal tissue was aggravated, and the content of SOD and the expression of sirt1 in renal tissue decreased (,P,<,0.01) . Moreover, Scr, SUA, UMA, levels of serum TNF-α and IL-6, content of MDA in renal tissue and acely FOXO1/FOXO1 were increased (,P,<,0.01) . Compared with the echinacoside group, the renal pathological damage of the echinacoside-EX527 group was aggravated. The content of SOD and the expression of sirt1 in renal tissue decreased (,P,<,0.01) . Scr, SUA, UMA, levels of serum TNF-α and IL-6, content of MDA in renal tissue and acely FOXO1/FOXO1 were increased (,P,<,0.01) . Compared with EX527 group, the pathological damage of kidney tissue of rats in echinacoside-EX527 group was alleviated, and the content of SOD and the expression of sirt1 in renal tissue were increased (,P,<,0.01) . Additionally, Scr, SUA, UMA, levels of serum TNF-α and IL-6, content of MDA in renal tissue and acely FOXO1/FOXO1 decreased (,P,<,0.01) .,Conclusion,2,Echinacoside may inhibit oxidative stress and inflammation by activating the sirt1/FOXO1 pathway to reduce diabetic renal injury.

关键词

松果菊苷糖尿病肾损伤sirt1/FOXO1通路大鼠

Keywords

echinacosidediabetes mellitusrenal injurysirt1/FOXO1 pathwayrat

references

XU J, LIU L Q, XU L L, et al. Metformin alleviates renal injury in diabetic rats by inducing Sirt1/FoxO1 autophagic signal axis[J].Clin Exp Pharmacol Physiol,2019,47(4): 599-608.

HU B, TONG F, XU L,et al. Role of calcium sensing receptor in streptozotocin-induced diabetic rats exposed to renal ischemia reperfusion injury[J].Kidney Blood Press Res, 2018, 43(1): 276-286.

ZHANG Y Y, TANG P M K, TANG P C T, et al. LRNA9884, a novel smad3-dependent long noncoding RNA, promotes diabetic kidney injury in db/db mice via enhancing MCP-1-dependent renal inflammation[J].Diabetes, 2019, 68(7): 1485-1498.

ZHANG J J, WANG L, GONG D J, et al. Inhibition of the SIRT1 signaling pathway exacerbates endoplasmic reticulum stress induced by renal ischemia/reperfusion injury in type 1 diabetic rats[J].Mol Med Rep, 2020, 21(2): 695-704.

BAI X Z, HE T, GAO J X, et al. Melatonin prevents acute kidney injury in severely burned rats via the activation of SIRT1[J/OL].Sci Rep, 2016[2020-02-23].https://pubmed.ncbi.nlm.nih.gov/27599451/https://pubmed.ncbi.nlm.nih.gov/27599451/.

CHUANG P Y, CAI W J, LI X Z, et al. Reduction in podocyte SIRT1 accelerates kidney injury in aging mice[J].Am J Physiol Renal Physiol, 2017, 313(3): F621-F628.

FU Z F, HAN L F, ZHANG P, et al. Cistanche polysaccharides enhance echinacoside absorption in vivo and affect the gut microbiota[J].Int J Biol Macromol, 2020(149): 732-740.

朱四民，王会芳，林凤平，等. 葛根提取物通过调控NOD样受体蛋白3/半胱氨酸天冬氨酸蛋白酶1通路减轻糖尿病大鼠肾损伤的研究[J].中国糖尿病杂志,2019,27(11): 852-857.

赵东海，赵贵芳，马帅，等. 松果菊苷对醋酸铅致生精功能损伤小鼠的治疗作用[J].上海中医药杂志,2018,52(6): 83-86.

陈树利，张丽. SIRT1通路介导紫檀芪减轻大鼠急性心肌梗死损伤研究[J].长治医学院学报,2018,32(1): 8-11.

PERCO P, MAYER G. Molecular, histological, and clinical phenotyping of diabetic nephropathy: valuable complementary information?[J].Kidney Int, 2018, 93(2): 308-310.

EL-HORANY H E, ABD-ELLATIF R N, WATANY M, et al. NLRP3 expression and urinary HSP72 in relation to biomarkers of inflammation and oxidative stress in diabetic nephropathy patients[J].IUBMB Life, 2017, 69(8): 623-630.

XU H B, QIN W Y, HU X, et al. Lentivirus-mediated overexpression of OTULIN ameliorates microglia activation and neuroinflammation by depressing the activation of the NF-κB signaling pathway in cerebral ischemia/reperfusion rats[J].J Neuroinflammation, 2018, 15(1): 83-99.

HSU R K, HSU C Y, MCCULLOCH C E, et al. Research-based versus clinical serum creatinine measurements and the association of acute kidney injury with subsequent kidney function: findings from the chronic renal insufficiency cohort study[J].Clin Kidney J, 2020, 13(1): 55-62.

ELGAMAL H, MUNUSAMY S. Aldose reductase as a drug target for treatment of diabetic nephropathy: promises and challenges[J].Protein Pept Lett, 2017, 24(1): 71-77.

张雪，郝亚荣，唐凤娟. 松果菊苷对2型糖尿病小鼠血脂代谢的影响[J].医学研究杂志,2018,47(3): 47-50.

雷箴，温韬. 松果菊苷对刀豆蛋白A所致急性肝损伤小鼠的保护作用及对细胞外组蛋白的影响[J].解放军医学杂志,2016,41(2): 97-102.

YAO H L, YAO Z, ZHANG S C, et al. Upregulation of SIRT1 inhibits H2O2induced osteoblast apoptosis via FoxO1/βcatenin pathway[J].Mol Med Rep, 2018, 17(5): 6681-6690.

HONG Q, ZHANG L, DAS B, et al. Increased podocyte sirtuin-1 function attenuates diabetic kidney injury[J].Kidney Int, 2018, 93(6): 1330-1343.

Views

408

下载量

CSCD

CNKI被引量

Alert me when the article has been cited

提交

Tools

Publicity Resources

Effects of Chaihu Shugan Powder on AMPK/SIRT3 signaling pathway in rats with functional dyspepsia

Acupuncture modulates expression of circHDAC2 in hippocampus of cerebral ischemia reperfusion injury rats against neurological damage

Gantangyi Recipe improving abnormal glucose metabolism of hepatocyte peroxidative damage in vitro

Discussion on pathogenesis and treatment of diabetes based on turbid toxin theory

Xie Jingri’s experience in treating diabetic gastroparesis 

Related Author

No data

Related Institution

Gastroenterology Department，Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine

Department of Traditional Chinese Medicine， Hunan Provincial Maternal and Child Health Care Hospital

School of Acupuncture-Moxibustion and Tuina， Chengdu University of Traditional Chinese Medicine

Rehabilitation Center， Second Affiliated Hospital of Anhui University of Traditional Chinese Medicine

School of Acupuncture， Massage and Rehabilitation， Hunan University of Chinese Medicine

⁰