WIN55212-2 alleviates acute kidney injury in septic mice by regulating the AKT/mTOR/PFKFB3 signaling pathway
10.16016/j.2097-0927.202307071
- VernacularTitle:WIN55212-2通过调控AKT/mTOR/PFKFB3信号通路减轻脓毒症小鼠急性肾损伤
- Author:
Xupeng DONG
1
;
Qianwen DUAN
;
Yuan MA
;
Che LIU
;
Yu GONG
;
Yuqing MA
Author Information
1. 730000 兰州,兰州大学第一临床医学院
- Keywords:
sepsis;
acute kidney injury;
aerobic glycolysis;
AKT/mTOR
- From:
Journal of Army Medical University
2024;46(10):1100-1106
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects of cannabinoid receptor agonist,WIN55212-2(WIN),on acute kidney injury(AKI)in mice with sepsis and its underlying mechanism.Methods Twenty-four healthy male mice were divided into(n=6):Control group,sepsis group(LPS group),sepsis+WIN55212-2 group(LPS+WIN group)and sepsis+WIN55212-2+mTOR activator MHY1485 group(LPS+WIN+MHY group).The sepsis model was constructed by intraperitoneal injection of LPS.After the tissue and blood samples were harvested in 24 h after modeling,ELISA was used to determine the contents of IL-1β,IL-18 and lactate dehydrogenase A(LDHA)in the renal tissues,as well as Scr,kidney injury molecule-1(KIM-1)and lactic acid(LA)in the serum.HE staining was employed to observe the pathological changes of kidney tissue and Paller score was calculated.The expression of p-AKT,p-Mtor and 6-phosphofructokinase-2/fructose-2,6-biphosphatase 3(PFKFB3)in the renal tissues was detected by Western blotting.Results Compared with the Control group,the LPS group had obvious kidney tissue damage,increased Paller score(P＜0.05),increased serum contents of lactic acid,Scr and KIM-1(P＜0.05),up-regulated contents of LDHA,IL-1β and IL-18 in the renal tissues(P＜0.05),and elevated expression levels of p-AKT,p-Mtor and PFKFB3 in the renal tissues(P＜0.05).Milder pathological injury in kidney tissue,decreased Paller score(P＜0.05),reduced contents of lactic acid,Scr and KIM-1(P＜0.05),decreased contents of LDHA,IL-1β and IL-18(P＜0.05),and lower expression of p-AKT,p-Mtor and PFKFB3 were observed in the LPS+WIN group than the LPS group(P＜0.05).The LPS+WIN+MHY group had notably higher Paller score(P＜0.05),raised contents of lactic acid,Scr and KIM-1(P＜0.05),increased contents of LDHA,IL-1β and IL-18(P＜0.05),and up-regulated expression of p-AKT,p-Mtor and PFKFB3(P＜0.05)when compared with the LPS+WIN group.Conclusion WIN can alleviate AKI in sepsis,and it may reduce the level of glycolysis in renal tissue,and alleviate inflammation through inhibiting AKT/Mtor/PFKFB3 signaling pathway.
