Interleukin-15 pretreatment regulates sepsis induced cardiomyocyte apoptosis and its related mechanisms
10.3969/j.issn.1009-0754.2024.07.004
- VernacularTitle:白细胞介素-15预处理调控脓毒症诱导的心肌细胞凋亡及其相关机制研究
- Author:
Hui LI
1
;
Chi XIONG
;
Lang LI
;
Yandan GUO
;
Yuan ZHANG
;
Yumei WANG
;
Wenping XU
Author Information
1. 510010 广东 广州,中国人民解放军南部战区总医院健康医学科
- Keywords:
Interleukin-15;
Sepsis;
Cardiomyocyte apoptosis;
Oxidative stress
- From:
Journal of Navy Medicine
2024;45(7):683-689
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the effect of interleukin-15(IL-15)on lipopolysaccharide(LPS)-induced apoptosis of septic cardiomyocytes and its related mechanism.Methods H9C2 cells were divided into control group(H9C2 cells in conventional culture),apoptosis group(LPS-induced myocardial cell injury model was established),and intervention group(10 ng/ml recombinant rat IL-15 was used in myocardial H9C2 cell injury model for 6 h).The effects of IL-15 on H9C2 cell proliferation and apoptosis were detected by methyl thiazolyl tetrazolium(MTT)assay and flow cytometry,the level of mitochondrial membrane potential was detected by staining of tetramethylrhodamine ethyl ester(TMRE).The sepsis mouse model was established by intraperitoneal injection of 10 mg/kg LPS,and 100 μl of normal saline containing 100 μg/ml IL-15 was injected intraperitoneally.HE staining was used to evaluate the pathological injury of mouse myocardium.The indexes of oxidative stress in mouse myocardium were detected by ELISA.The effects of IL-15 on the expression of heme oxygenase 1(HO-1)and NF-E2-related factor 2(Nrf2)mRNAs and proteins in myocardium of mouse sepsis model were detected by real-time fluorescence quantitative PCR and Western bloting.Results The apoptosis rate of H9C2 cells in the apoptosis group was significantly higher than that in the control group(47.9%±5.1%vs.2.1%±0.3%,P<0.05).The apoptosis rate of H9C2 cells in the intervention group was 20.7%±2.7%,which was significantly lower than that in the apoptosis group(P<0.05).LPS could significantly inhibit the proliferation of myocardial cells,while IL-15 could inhibit LPS-induced decrease in myocardial cell viability(P<0.05).The relative mitochondrial membrane potential of myocardial H9C2 cells in the apoptosis group was significantly lower than that in the control group(2.6±4.6 vs.7.4±5.2,P<0.05).The relative mitochondrial membrane potential of myocardial H9C2 cells in the intervention group was 4.2±4.9,which was significantly higher than that in the apoptosis group(P<0.05).LPS significantly enhanced the loss of mitochondrial membrane potential of myocardial H9C2 cells,and IL-15 intervention weakened the loss of mitochondrial membrane potential of H9C2 cells induced by LPS(P<0.05).HE staining revealed obvious myocardial tissue damage and inflammatory cell infiltration in mouse sepsis model.IL-15 ameliorated LPS-induced myocardial injury in mice.The expression levels of superoxide dismutase(SOD)and total antioxidant capacity(T-AOC)in myocardium of sepsis mice were significantly lower than those in normal mice,while the expression level of malondialdehyde(MDA)in sepsis mice was significantly higher than that in normal mice(P<0.05).After IL-15 intervention,the expression of SOD and T-AOC in myocardium of sepsis mice was increased,and the expression of MDA was decreased(P<0.05).The mRNA and protein expression levels of HO-1 and Nrf2 were low in myocardium of normal mice.The mRNA and protein expression levels of HO-1 and Nrf2 in myocardium of sepsis mice were significantly higher than those in normal mice(P<0.05).After IL-15 intervention,the mRNA and protein expression levels of HO-1 and Nrf2 were significantly increased in myocardium of sepsis mice(P<0.05).Conclusion IL-15 can protect cardiomyocyte apoptosis induced by sepsis and decrease myocardial injury in sepsis mice.The mechanism may be related to the activation of HO-1/Nrf2 signaling pathway and the inhibition of myocardial oxidative stress in septic mice.
