Myocardial protective effect of sivelestat sodium in rat models with sepsis-induced myocarditis

Rujun Zhang; Xiaoxin Gao; Fuxing Hu; Qingan Chen; Zhenlin Lei; Yanan Yang; Jia Tian

doi:10.21037/jtd-22-1309

Myocardial protective effect of sivelestat sodium in rat models with sepsis-induced myocarditis

J Thorac Dis. 2022 Oct;14(10):4003-4011. doi: 10.21037/jtd-22-1309.

Authors

Rujun Zhang¹, Xiaoxin Gao², Fuxing Hu³, Qingan Chen², Zhenlin Lei², Yanan Yang², Jia Tian²

Affiliations

¹ Department of Cardiology, Hainan Province Clinical Medical Center, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, China.
² Intensive Medical Unit, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, China.
³ Intensive Medical Unit, Hainan Second People's Hospital, Wuzhishan, China.

Abstract

Background: The incidence of sepsis has been steadily increasing worldwide, and the heart is one of the target organs that can be easily damaged by sepsis. At present, antibiotics and organ function support are the main treatment options for sepsis and multiple system organ dysfunction, but are still under investigation.

Methods: Fifty rats were randomly divided into the sham operation group, sepsis group, sivelestat sodium low-dose (L) group (administered with sivelestat sodium 1.6 mg/kg), sivelestat sodium middle-dose (M) group (administered with sivelestat sodium 4.8 mg/kg), and sivelestat sodium high-dose (H) group (administered with sivelestat sodium 10 mg/kg). Morphological changes of myocardial cells and the distribution of extracellular signal-regulated kinase (ERK)1/2 proteins were observed by light microscope. Serum troponin-T, creatine kinase isoenzyme MB, brain natriuretic peptide, interleukin (IL)-6, tumor necrosis factor-α, and IL-1β levels and changes in cardiac function indicators were measured. The protein expressions of Bax, Bcl-2, and ERK1/2 were detected by Western blotting.

Results: Compared with the sham operation group, the release of inflammatory factors in the sepsis group increased; the protein expressions of Bax, Bcl-2, and ERK1/2 increased; left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), and maximum rate of LVP rise (+dp/dtmax) level decreased, whereas -dp/dtmax increased. In the sivelestat sodium groups, the release of inflammatory factors decreased; Bax expression decreased, whereas Bcl-2 and ERK1/2 protein expressions increased; LVSP, LVEDP, and +dp/dtmax increased, whereas -dp/dtmax decreased. In addition, all of these changes occurred in a dose-dependent manner.

Conclusions: Sivelestat sodium can effectively lower the expressions of inflammatory factors and improve cardiac function. It can act on the ERK1/2 signaling pathway to exert its cardiomyocyte-protective effect, and the activation of this signaling pathway can offer potential treatment sites for septic myocarditis.

Keywords: Sepsis; cardiac function; inflammatory factors; signaling pathway; sivelestat sodium.