隐丹参酮调节Sirt1/FoxO1信号通路对高糖诱导的肾小球内皮细胞损伤的影响

doi:10.3969/j.issn.1006-6233.2023.06.02

摘要
图/表
参考文献
相关文章 (15)

全文: PDF (2067 KB) HTML (1 KB)
输出: BibTeX | EndNote (RIS)

摘要 目的: 探讨隐丹参酮(CT)调节沉默信息调节因子1(Sirt1)/叉头框蛋白O1(FoxO1)信号通路对高糖诱导的肾小球内皮细胞(GEC)损伤的影响。方法: 将GEC分为对照组(NR组,5mmoL/L D-葡萄糖)、高糖组(HG组,30mmoL/L D-葡萄糖)、L-CT组(1 μmoL/L CT+30mmoL/L D-葡萄糖处理GEC)、M-CT组(5 μmoL/L CT+30mmoL/L D-葡萄糖处理GEC)、H-CT组(10 μmoL/L CT+30mmoL/L D-葡萄糖处理GEC)和SIRT1-IN-1 组(10 μmoL/L CT+30mmoL/L D-葡萄糖+0.05moL/L Sirt1/FoxO1信号通路抑制剂SIRT1-IN-1处理GEC);MTT法检测CT对GEC细胞毒性和细胞活力的影响;ELISA法检测GEC炎症因子水平和氧化应激指标水平;流式细胞术检测GEC凋亡;Western blot法检测细胞中自噬、凋亡、纤维化因子和Sirt1/FoxO1通路相关蛋白表达。结果: 0~40 μmoL/L CT对GEC无明显毒性影响。与NR组相比,HG组OD₅₇₀值、SOD含量、Bcl-2、Beclin1、LC3-Ⅱ/Ⅰ、p-Sirt1/Sirt1、p-FoxO1/FoxO1蛋白水平显著下降(P<0.05),GEC凋亡率、Bax、cleaved-Caspase-3、 Col-I 、TGF-β1蛋白水平、 IL-6、IL-8、TNF-α、MDA含量显著上调(P<0.05);与HG组相比,L-CT组、M-CT组、H-CT组增殖活性、自噬蛋白、通路蛋白水平显著升高(P<0.05),炎性反应、氧化应激、纤维化因子蛋白水平、凋亡率显著下降(P<0.05);SIRT1-IN-1消除了CT对GEC的有利影响。结论: CT可能通过上调Sirt1/FoxO1信号通路改善高糖诱导的GEC损伤。

	服务

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章

关键词 ：隐丹参酮, Sirt1/FoxO1信号通路, 肾小球内皮细胞, 氧化应激, 自噬

Abstract：Objective: To investigate the effect of cryptotanshinone (CT) on the injury of glomerular endothelial cells (GEC) induced by high glucose by regulating silent information regulator 1 (Sirt1)/forkhead box protein O1 (FoxO1) signal pathway. Methods: GEC was divided into control group (NR group,5mmol/L D-glucose), high glucose group ( HG group, 30mmol/L D-glucose), L-CT group ( GEC treated with 1 μmol/L CT+30 mmol/L D-glucose), M-CT group (GEC treated with 5 μmol/L CT+30 mmol/L D-glucose), H-CT group (GEC treated with 10 μmol/L CT+30 mmol/L D-glucose), and SIRT1-IN-1 group (GEC treated with 10 μmol/L CT+30 mmol/L D-glucose+0.05 mol/L Sirt1/FoxO1 signal pathway inhibitor SIRT1-IN-1); MTT assay was used to detect the effects of CT on the cytotoxicity and viability of GEC cells; the levels of GEC inflammatory factors and oxidative stress indicators were detected by ELISA; the apoptosis of GEC was detected by flow cytometry; Western blot was used to detect the expression of autophagy, apoptosis, fibrosis factors and Sirt1/FoxO1 pathway related proteins in cells. Results: 0-40 μmol/L CT had no obvious toxic effect on GEC. Compared with NR group, OD₅₇₀ value, content of SOD, the levels of Bcl-2, Beclin1, LC3-Ⅱ/Ⅰ, p-Sirt1/Sirt1, p-FoxO1/FoxO1 proteins in HG group decreased obviously (P<0.05), the apoptosis rate of GEC, the levels of Bax, cleaved Casase-3, Col-I, TGF-1 proteins, contents of IL-6, IL-8, TNF-α, and MDA increased obviously (P<0.05); compared with HG group, the proliferation activity, the levels of autophagic protein and pathway protein in L-CT group, M-CT group and H-CT group increased obviously (P<0.05), the levels of inflammatory reaction, oxidative stress, fibrosis factor protein and apoptosis rate decreased obviously (P<0.05); SIRT1-IN-1 eliminated the beneficial effect of CT on GEC. Conclusion: CT may improve GEC injury induced by high glucose by up-regulating Sirt1/FoxO1 signal pathway.

Key words： Cryptotanshinone Sirt1/FoxO1 signal pathway Glomerular endothelial cells Oxidative stress Autophagy

基金资助:河北省中医药管理局中医药类科研计划项目,(编号:2019206)

引用本文:

武文印, 武禹佳, 李艳, 梁进颖. 隐丹参酮调节Sirt1/FoxO1信号通路对高糖诱导的肾小球内皮细胞损伤的影响[J]. 河北医学, 2023, 29(6): 887-892.
WU Wenyin, WU Yujia, LI Yan. Effect of Cryptotanshinone on High Glucose-Induced Glomerular Endothelial Cell Injury through the Regulation of Sirt1/FoxO1 Signaling Pathway. HeBei Med, 2023, 29(6): 887-892.

链接本文:

http://www.hbyxzzs.cn/CN/10.3969/j.issn.1006-6233.2023.06.02 或 http://www.hbyxzzs.cn/CN/Y2023/V29/I6/887

[1] Orr P,Shank BC,Hickson S,et al.Clinical management of glomerular diseases[J].Nurs Clin North Am,2018,53(4):551-567.
[2] Daehn IS,Duffield JS.The glomerular filtration barrier:a structural target for novel kidney therapies[J].Nat Rev Drug Discov,2021,20(10):770-788.
[3] Sun L,Sun C,Zhou S,Zhang L,et al.Tamsulosin attenuates high glucose- induced injury in glomerular endothelial cells[J].Bioengineered,2021,12(1):5184-5194.
[4] Song M,Chen L,Zhang L,et al.Cryptotanshinone enhances wound healing in type 2 diabetes with modulatory effects on inflammation,angiogenesis and extracellular matrix remodelling[J].Pharm Biol,2020,58(1):845-853.
[5] Xu J,Liu LQ,Xu LL,et al.Metformin alleviates renal injury in diabetic rats by inducing Sirt1/FoxO1 autophagic signal axis[J].Clin Exp Pharmacol Physiol,2020,47(4):599-608.
[6] Shan MY,Dai Y,Ren XD,et al.Berberine mitigates nonalcoholic hepatic steatosis by downregulating SIRT1-FoxO1-SREBP2 pathway for cholesterol synthesis[J].Integr Med,2021,19(6):545-554.
[7] Lo SH,Hsu CT,Niu HS,et al.Cryptotanshinone inhibits STAT3 signaling to alleviate cardiac fibrosis in type 1-like diabetic rats[J].Phytother Res,2017,31(4):638-646.
[8] Mukohara S,Mifune Y,Inui A,et al.In vitro and in vivo tenocyte-protective effectiveness of dehydroepiandrosterone against high glucose-induced oxidative stress[J].BMC Musculoskelet Disord,2021,22(1):519-529.
[9] Tang PM,Nikolic-Paterson DJ,Lan HY.Macrophages:versatile players in renal inflammation and fibrosis[J].Nat Rev Nephrol,2019,15(3):144-158.
[10] Koch EAT,Nakhoul R,Nakhoul F,et al.Autophagy in diabetic nephropathy:a review[J].Int Urol Nephrol,2020,52(9):1705-1712.
[11] He W,Zhang A,Qi,et al. FoxO1,a potential therapeutic target,regulates autophagic flux oxidative stress mitochondrial dysfunction and apoptosis in human cholangiocarcinoma QBC939 cells[J].Cell Physiol Biochem,2018,45(4):1506-1514.