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| Effect of Cryptotanshinone on High Glucose-Induced Glomerular Endothelial Cell Injury through the Regulation of Sirt1/FoxO1 Signaling Pathway |
| WU Wenyin, WU Yujia, LI Yan |
| Tangshan Traditional Chinese Medicine Hospital, Hebei Tangshan 063000, China |
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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.
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[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. |
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2023, Vol. 29 
