Impacts of Artesunate on the Formation of Kidney Oxalate Stones by Regulating the PI3K/Akt Signaling Pathway
10.11969/j.issn.1673-548X.2024.10.027
- VernacularTitle:青蒿琥酯调节PI3 K/Akt信号通路对肾草酸结石形成的影响
- Author:
Yuanyuan WANG
1
;
Ding LI
;
Chuangui LI
Author Information
1. 071000 保定市第一中心医院泌尿外一科
- Keywords:
Artesunate;
Phosphatidylinositol 3 kinase/protein kinase B;
Kidney stones
- From:
Journal of Medical Research
2024;53(10):149-156,173
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the impacts of artesunate(Art)on the formation of kidney stones and the phosphatidylinositol 3 kinase(PI3K)/protein kinase B(Akt)signaling pathway.Methods Rats were randomly divided into the Control group,Model group,Artesunate low-dose group(ART-L group),artesunate high-dose group(ART-H group),artesunate high-dose+PI3K in-hibitor group(Art+LY294002 group).The rat model of kidney stone was established by drinking water with ethylene glycol and injecting sodium oxalate intraperitoneally.A kidney stone cell model was established by exposing HK-2 cells to 200 mg/L calcium oxalate mono-hydrate crystals and 2 mmol/L oxalate.The levels of Ca2+and oxalic acid(Ox)in urine and serum creatinine(Scr)and blood urea ni-trogen(BUN)were detected;Pizzolato staining was applied to observe the deposition of calcium salts in renal tissues;the pathological morphology in renal tissues was detected by HE staining;malondialdehyde(MDA)and superoxide dismutase(SOD)kits were used to detect the levels of MDA and SOD in renal tissue and HK-2 cells;ELISA method was applied to detect TNF-α,IL-1βand IL-6 in renal tissue and HK-2 cells;fluorescence quantification was applied to detect the levels of Bax,caspase-3,PI3K and Akt;immunohis-tochemical and Western blot were applied to detect the expression levels of PI3K and Akt proteins in the renal tissues.HK-2 cell apopto-sis was measured by flow cytometry.Results Compared with the Model group,Ca2+,Ox,Scr,BUN,the level of MDA,TNF-α,IL-1 β,IL-6 in renal tissue and HK-2 cells,the expression of Bax,caspase-3 in renal tissue decreased in Art-L and Art-H groups,the level of SOD,PI3K,and Akt in renal tissue and HK-2 cells increased(P<0.05);compared with the Art-H group,Ca2+,Ox,Scr,BUN,the level of MDA,TNF-α,IL-1 β,IL-6 in renal tissue and HK-2 cells,the expression of Bax,caspase-3 in renal tis-sue increased in the Art+LY294002 group,the level of SOD,PI3K and Akt in renal tissue and HK-2 cells decreased(P<0.05).Conclusion Artesunate can inhibit the formation of kidney stones;its inhibition of stone formation may be produced through the mecha-nism of up-regulating the PI3K/Akt signaling pathway.