Silencing Cardiac Troponin I-Interacting Kinase Reduces Lipopolysaccharide-Induced Sepsis-Induced Myocardial Dysfunction in Rat by Regulating Apoptosis-Related Proteins.

Dong Yang,Xiaomin Liu,Haixia Qian,Yanzhou Jiang,Liguo Mi,Antonis Gargalionis

doi:10.1155/2021/5520051

Abstract

The aim of this study was to investigate the effect of cardiac troponin I-interacting kinase (TNNI3K) on sepsis-induced myocardial dysfunction (SIMD) and further explore the underlying molecular mechanisms. In this study, a lipopolysaccharide- (LPS-) induced myocardial injury model was used. qRT-PCR was performed to detect the mRNA expression of TNNI3K. Western blot was conducted to quantitatively detect the expression of TNNI3K and apoptosis-related proteins (Bcl-2, Bax, and caspase-3). ELISA was performed to detect the content of lactate dehydrogenase (LDH) and creatine kinase (CK). TUNEL assay was used to detect the apoptosis of H9C2 cells. In LPS-induced H9C2 cells, TNNI3K was up regulated. Besides, the CK activity, the content of LDH, and the apoptosis of H9C2 cells were significantly increased after treatment with LPS. Silencing TNNI3K decreased the LDH release activity and CK activity and inhibited apoptosis of H9C2 cell. Further research illustrated that si-TNNI3K promoted the protein expression of Bcl-2 and decreased the protein expression of Bax and cleaved caspase-3. The study concluded that TNNI3K was upregulated in LPS-induced H9C2 cells. Importantly, functional research findings indicated that silencing TNNI3K alleviated LPS-induced H9C2 cell injury by regulating apoptosis-related proteins.

Highlights

Sepsis can lead to multiorgan dysfunction, among which sepsis-induced myocardial dysfunction (SIMD) is a serious complication [1]
In lactate dehydrogenase (LDH) assay, we found that the LDH release activity from H9C2 cells was remarkably increased, suggesting that LPS aggravated H9C2 cell injury (P < 0:01, Figure 2(b))
We confirmed that LPS induced an increase in LDH release activity, creatine kinase (CK) activity, and apoptosis in rat cardiomyocytes, which is consistent with a previous study

Summary

Introduction

Sepsis can lead to multiorgan dysfunction, among which sepsis-induced myocardial dysfunction (SIMD) is a serious complication [1]. Diastolic dysfunction occurs and diastolic compliance decreases, eventually leading to total heart failure [2]. Two clinical studies have shown that patients with septic associated systolic dysfunction (sepsis induced cardiomyopathy) have an increased mortality rate of up to 80%, compared with patients with sepsis with normal systolic function [4, 5]. Fluid resuscitation and contractile drugs such as dobutamine or levosimendan are the main strategies for the treatment of SIMD. Fluid overload can be harmful to the heart, and the effectiveness of muscle contractile agents remains controversial [6, 7]. It is urgent to explore new treatment methods for SIMD

Objectives

Results

Conclusion