Role of Thrombospondin‑1 in sepsis‑induced myocardial injury.

Abstract

Sepsis often causes myocardial injury with a high mortality. The aim of the present study was to investigate the effects of thrombospondin‑1(THBS1) on myocardial cell injury, oxi‑dative stress and apoptosis in sepsis. The expression of THBS1 mRNA in lipopolysaccharide(LPS)‑induced mouse primary cardiomyocytes was detected by reverse transcription‑quantitative PCR(RT‑qPCR). A eukaryotic small interfering(si)RNA expression vector was constructed and transfected into myocardial cells to knockdown THBS1 mRNA expression, which was confirmed by RT‑qPCR. Four in vitro experimental groups were used: i)Control, ii)LPS, iii)THBS1 siRNA(siTHBS1) and iv)siTHBS+LPS. ELISA was used to detect cardiac troponinI(cTnI), pro‑brain natriuretic peptide(proBNP), reactive oxygen species(ROS), caspase‑3, IL‑6 and TNF‑α. Invivo mouse sepsis models were also established, and H&E, TUNEL and caspase‑3 staining were used to evaluate myocardial cell injury and apoptosis. Clinical samples were collected to analyze the serum THBS1levels and to associate this with the prognosis of patients with sepsis‑induced myocardial injury. The expression level of THBS1 mRNA in myocardial cells induced by LPS was increased, and the serum THBS1level in patients with myocardial injury in sepsis was also significantly increased compared with patients without sepsis‑induced myocardial injury. In the siTHBS1‑treated mice with myocardial injury, the levels of cTnI and proBNP were significantly decreased, the levels of the inflammatory cytokinesIL‑6 and TNF‑α were significantly decreased, ROS were significantly decreased, caspase‑3 was significantly decreased, and myocardial cell apoptosis was also reduced, compared with the LPSgroup. Data from the present study suggested that THBS1 may be closely related to the biological behavior of myocardial cells and may be a therapeutic target for myocardial injury in sepsis.