Inhibitory effect and mechanism of caudal vein injection of SMP30 on myocardial injury in mice with sepsis
HU Peijing
ZHANG Xuedan
DU Zhankui
CAO Biao
Abstract：Objective To observe the inhibitory effect of caudal vein injection of senescence marker protein 30(SMP30)on myocardial injury in septic mice and to explore its mechanism.Methods Sixty male C57BL/6 mice were randomly divided into the Con+empty vector group,LPS+empty vector group,and LPS+SMP30 group,with 20 mice in each.Mice in the Con+empty vector group and LPS+empty vector group were injected with adeno-null associated virus vec-tor via the tail vein,and mice in the LPS+SMP30 group were injected with SMP30 adeno-associated virus vector via the tail vein.After 2 weeks of adeno-associated virus vector injection,mice in the LPS+empty vector group and LPS+SMP30 group were intraperitoneally injected with lipopolysaccharide(LPS)to establish the sepsis models,while mice in the Con+empty vector group were given intraperitoneal injection of the same volume of normal saline.Left ventricular ejection fraction(LVEF)and left ventricular fraction shortening(LVFS)were measured by echocardiography at 24 h after LPS injection.Serum and heart tissues were collected after the mice were killed,and serum levels of creatine kinase-MK(CK-MB),lac-tic dehydrogenase(LDH)and cTnI,and myocardial levels of malondialdehyde(MDA),superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)were detected by ELISA.TUNEL staining was used to detect cardiomyocyte apoptosis.Macrophage infiltration was detected by immunofluorescence staining.The myocardial reactive oxide species(ROS)pro-duction was detected by dihydroethidium fluorescent probe.Interleukin(IL)-1β,tumor necrosis factor(TNF)-α and IL-6 mRNA levels were detected by qRT-PCR.The protein expression levels of myocardial tissues SMP30,silent information regulator 1(SIRT1),Ac-NF-κB p65,and Ac-FOXO1 were detected by Western blotting.Results Compared with the Con+empty vector group,the values of LVEF and LVFS decreased,the levels of serum CK-MB,LDH and cTnI increased,the apoptosis rate increased,the myocardial macrophage infiltration was more obvious,the mRNA levels of IL-1β,IL-6,TNF-α increased,the productions of ROS and MDA increased,the activities of SOD and GSH-Px decreased,the expres-sion of SIRT1 down-regulated,and the expression levels of Ac-NF-κB p65 and Ac-FOXO1 increased in the LPS+empty vector group(all P<0.01).Compared with LPS+empty vector group,the values of LVEF and LVFS increased,the levels of serum CK-MB,LDH and cTnI decreased,the apoptosis rate decreased,the myocardial macrophage infiltration de-creased,the mRNA levels of IL-1β,IL-6,TNF-α decreased,the productions of ROS and MDA decreased,the activities of SOD and GSH-Px increased,the expression of SIRT1 increased,and the expression levels of Ac-NF-κB p65 and Ac-FOXO1 decreased in the LPS+SMP30 group(all P<0.01).Conclusion The caudal vein injection of SMP30 can up-reg-ulate SMP30 expression in mice with sepsis,inhibit myocardial inflammatory response and oxidative stress level,thereby alleviating myocardial injury,and its mechanism may be related to activating the SIRT1 signaling pathway.
Keywords：sepsissenescence marker protein 30myocardial injuryoxidative stressinflammationsilent in-formation regulator 1
Publication Date：2024-09-15
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：6( 41-46 )