Research on activating SIRT3 protein by marein to delay fibrosis damage induced by high glucose and palmitic acid in HBZY⁃1 cells

AMILA·Abulati; Feng GUO; Hongyan MA; Xinmin MAO; Lan YAO

doi:10.16305/j.1007-1334.2022.2012093

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Research on activating SIRT3 protein by marein to delay fibrosis damage induced by high glucose and palmitic acid in HBZY⁃1 cells

更新时间：2022-09-30

- Research on activating SIRT3 protein by marein to delay fibrosis damage induced by high glucose and palmitic acid in HBZY⁃1 cells
- Shanghai Journal of Traditional Chinese Medicine Vol. 56, Issue 9, Pages: 82-88(2022)
- 作者机构：
  
  1.新疆医科大学中医学院（新疆乌鲁木齐 830011）
  2.新疆特有药用资源利用省部共建国家重点实验室培育基地，中国科学院干旱区植物资源化学重点实验室，中国科学院新疆理化技术研究所（新疆乌鲁木齐 830011）
- 作者简介：
- 基金信息：
- DOI：10.16305/j.1007-1334.2022.2012093
  CLC：
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阿米拉·阿不拉提 ,郭凤,马洪艳,等.马里苷活化SIRT3蛋白延缓高糖及软脂酸诱导HBZY⁃1细胞纤维化损伤的研究[J].上海中医药杂志,2022,56(9):82-88.

AMILA·Abulati ,GUO Feng,MA Hongyan,et al.Research on activating SIRT3 protein by marein to delay fibrosis damage induced by high glucose and palmitic acid in HBZY⁃1 cells[J].Shanghai Journal of Traditional Chinese Medicine,2022,56(9):82-88.
阿米拉·阿不拉提 ,郭凤,马洪艳,等.马里苷活化SIRT3蛋白延缓高糖及软脂酸诱导HBZY⁃1细胞纤维化损伤的研究[J].上海中医药杂志,2022,56(9):82-88. DOI： 10.16305/j.1007-1334.2022.2012093.

AMILA·Abulati ,GUO Feng,MA Hongyan,et al.Research on activating SIRT3 protein by marein to delay fibrosis damage induced by high glucose and palmitic acid in HBZY⁃1 cells[J].Shanghai Journal of Traditional Chinese Medicine,2022,56(9):82-88. DOI： 10.16305/j.1007-1334.2022.2012093.

摘要

目的,2,研究马里苷介导沉默信息调节因子3（SIRT3）/固醇调节元件结合蛋白-1（SREBP-1）信号通路修复糖尿病肾病（DN）肾脏纤维化的作用。,方法,2,高糖（HG）和软脂酸（PA）诱导大鼠肾小球系膜细胞（HBZY-1）建立体外条件下DN模型，将细胞分为正常对照组、模型组和马里苷不同剂量组；倒置显微镜观察各组细胞数量及形态的变化；Western blot法检测各组细胞中SIRT3/SREBP-1通路蛋白、纤维化损伤相关蛋白转化生长因子-β1（TGF-β1）、磷酸化（p）-Smad同源物2（Smad2）、p-Smad3、Smad4的表达水平；采用Discovery studio软件将马里苷与SIRT3进行分子对接；免疫荧光法检测各组细胞中纤连蛋白（FN）和胶原Ⅳ（Collagen Ⅳ）的表达和定位。,结果,2,马里苷可抑制HG及PA诱导的HBZY-1细胞增殖，使细胞间隙增大，细胞密度降低；马里苷能下调模型细胞中SREBP-1、TGF-β1、p-Smad2、p-Smad3、Smad4蛋白的表达；马里苷能上调活性SIRT3表达，同时分子对接结果表明马里苷与SIRT3蛋白能较好结合；马里苷可抑制HG及PA诱导的细胞中FN和Collagen Ⅳ蛋白表达。,结论,2,马里苷可能通过活化SIRT3蛋白，介导SIRT3/SREBP-1通路，下调TGF-β1/Smads信号通路蛋白，进而减轻HG以及PA诱导HBZY-1细胞的肾脏炎症和纤维化损伤。

Abstract

Objective,2,To study the role of marein in mediating SIRT3/SREBP-1 signaling pathway to repair renal fibrosis in diabetic nephropathy （DN）.,Methods,2,Rats’ glomerular mesangial cells （HBZY-1） were induced by high glucose （HG） and palmitic acid （PA） to establish a DN model ,in vitro,. The cells were divided into normal control group， model group and different dosage groups of marein. Inverted microscope was used to observe the changes in the number and morphology of cells in each group. Western blot was used to detect the expression levels of SIRT3/SREBP-1 pathway protein， fibrosis damage-related proteins transforming growth factor-β1 （TGF-β1）， p-Smad2， p-Smad3 and Smad4 in each group. Discovery studio was used to molecularly dock marein with silent information regulator 3 （SIRT3）. Immunofluorescence method was used to detect the expression and localization of fibronectin （FN） and Collagen Ⅳ of cells in each group.,Results,2,Marein inhibited the proliferation of HBZY-1 cells induced by HG and PA， which increased the intercellular and decreased the cell density. Marein down-regulated the expression of SREBP-1， TGF-β1， p-Smad2， p-Smad3 and Smad4 proteins in model cells. Marein up-regulated the expression of active SIRT3， and the molecular docking results showed that marein and SIRT3 protein binded well. Marein inhibited the expression of FN and Collagen Ⅳ protein in cells induced by HG and PA.,Conclusion,2,Marein may reduce the kidney inflammation and fibrosis damage induced by HG and PA in HBZY-1 cells by activating SIRT3 protein， mediating the SIRT3/SREBP-1 pathway and down-regulating the TGF-β1/Smads signaling pathway protein.

关键词

糖尿病肾病肾脏纤维化马里苷两色金鸡菊药理作用中药研究

Keywords

diabetic nephropathyrenal fibrosismareinCoreopsis Tinctoriapharmacologic effecttraditional Chinese herbal medicine

references

CHEN L， YANG T， LU D W， et al. Central role of dysregulation of TGF-β/Smad in CKD progression and potential targets of its treatment［J］. Biomed Pharmacother， 2018， 101： 670‐681.

徐青云. 厄贝沙坦对2型糖尿病肾病患者肾功能及血清Cys-C、APN的影响［J］. 现代医药卫生，2020， 36（9）： 1382-1384.

陈忠英，巨超龙. 血清胱抑素C、β2微球蛋白及尿微量清蛋白与尿肌酐比值在早期2型糖尿病肾病患者诊断中的临床意义［J］. 陕西医学杂志，2017， 46（4）： 467-468.

KIM Y， PARK C W. New therapeutic agents in diabetic nephropathy［J］. Korean J Intern Med，2017， 32（1）： 11‐25.

SRIVASTAVA S P， LI J， KITADA M， et al. SIRT3 deficiency leads to induction of abnormal glycolysis in diabetic kidney with fibrosis［J］. Cell Death Dis， 2018， 9（10）： 997.

LOCATELLI M， ZOJA C， ZANCHI C， et al. Manipulating Sirtuin 3 pathway ameliorates renal damage in experimental diabetes［J］. Sci Rep， 2020， 10（1）： 8418.

GUO D L， BELL E H， MISCHEL P， et al. Targeting SREBP-1-driven lipid metabolism to treat cancer［J］. Curr Pharm Des， 2014， 20（15）： 2619-2626.

WANG T N， CHEN X， LI R， et al. SREBP-1 mediates angiotensin Ⅱ-induced TGF-β1 upregulation and glomerular fibrosis［J］. J Am Soc Nephrol， 2015， 26（8）： 1839-1854.

阿米拉·阿不拉提，张楠楠，古丽拜克热木·热合曼，等. 马里苷通过AMPK通路抑制高糖软脂酸诱导大鼠肾小球系膜细胞氧化应激及炎症损伤的作用机制［J］. 中国药理学通报，2019， 35（8）： 1133-1137.

JIANG B P， LE L， ZHAI W， et al. Protective effects of marein on high glucose-induced glucose metabolic disorder in HepG2 cells［J］. Phytomedicine，2016， 23（9）： 891-900.

GUO Y L， RAN Z， ZHANG Y W， et al. Marein ameliorates diabetic nephropathy by inhibiting renal sodium glucose transporter 2 and activating the AMPK signaling pathway in db/db mice and high glucose-treated HK-2 cells［J］. Biomed Pharmacother， 2020， 131： 110684.

QIAN X， HE L L， HAO M， et al. YAP mediates the interaction between the Hippo and PI3K/Akt pathways in mesangial cell proliferation in diabetic nephropathy［J］. Acta Diabetologica， 2020， 58（1）： 47-62.

阿米拉·阿不拉提，范雪梅，毛新民，等. 两色金鸡菊黄酮成分对高糖高脂诱导的细胞模型能量代谢紊乱的影响［J］. 中国中医药信息杂志，2020， 27（5）： 35-41.

BONIAKOWSKI A E， DENDEKKER A D， DAVIS F M， et al. SIRT3 regulates macrophage-mediated inflammation in diabetic wound repair［J］. J Invest Dermatol， 2019， 139（12）： 2528-2537.

程玲莉，杨定平. 线粒体SIRT3在肾脏疾病中的研究进展［J］. 医学综述，2020， 26（13）： 2502-2506.

ZHAI M G， LI B Y， DUAN W X， et al. Melatonin ameliorates myocardial ischemia reperfusion injury through SIRT3-dependent regulation of oxidative stress and apoptosis［J/OL］. J Pineal Res， 2017 ［2021-05-24］. https：//pubmed.ncbi.nlm.nih.gov/28500761/https://pubmed.ncbi.nlm.nih.gov/28500761/.

DOROTEA D， KOYA D， HA H. Recent insights into SREBP as a direct mediator of kidney fibrosis via lipid-independent pathways［J］. Front Pharmacol， 2020， 11： 265.

YING H Z， ZANG J N， DENG L L， et al. Pentamethylquercetin reduces fat deposition via Sirt1-mediated pathways in male obese mice induced by a high fat diet［J］. Food Chem Toxicol， 2013， 62： 463-469.

LO A K， LUNG R W， DAWSON C W， et al. Activation of sterol regulatory element-binding protein 1（SREBP1）-mediated lipogenesis by the Epstein-Barr virus-encoded latent membrane protein 1（LMP1） promotes cell proliferation and progression of nasopharyngeal carcinoma［J］. J Pathol， 2018， 246（2）： 180-190.

焦晓翠. Sirt3对糖尿病肾小管氧化损伤的影响及分子机制的研究［D］. 石家庄：河北医科大学，2017.

LOEFFLER I， LIEBISCH M， ALLERT S， et al. FSP1-specific SMAD2 knockout in renal tubular， endothelial， and interstitial cells reduces fibrosis and epithelial-to-mesenchymal transition in murine STZ-induced diabetic nephropathy［J］. Cell Tissue Res， 2018， 372（1）： 115-133.

CHEN T S， LI J Y， LIU J N， et al. Activation of SIRT3 by resveratrol ameliorates cardiac fibrosis and improves cardiac function via the TGF-β/Smad3 pathway［J］. Am J Physiol Heart Circ Physiol， 2015， 308（5）： H424-H434.

DRAGOŞ D， MANEA M M， TIMOFTE D， et al. Mechanisms of herbal Nephroprotection in diabetes mellitus［J］. J Diabetes Res， 2020， 2020： 5710513.

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