| Objectives: Sepsis is a devastating medical problem, representing one of the leading cause of high morbidity and mortality in hospitalized patients around the world. It is initially triggered by bacterial infection which subsequently results in a systemic inflammatory response and progressive organ dysfunction with the most notably the cardiovascular system. Myocardial dysfunction is a recognized manifestation of sepsis and septic shock. Studies have also shown that 40%-50% of septic patients have diversely myocardial dysfunction, and the mortality ranging from 70% to 90% in contrast with 20% without myocardial injury in septic patients. While significant efforts have been made in diagnostic and therapeutic approaches, sepsis is still a major healthcare problem, thus making effective therapeutic remedy rather challenging. Hence, to reduce the morbidity and mortality in septic patients, there is an urgent assignment to identify new therapeutic strategies of myocardial injury.So far, multiple human mi RNAs have been shown to be dysregulated in sepsis, which provide values for diagnosis and prognosis of sepsis. Recent studies have confirmed that mi RNAs relate to cardiac disorders. Mi RNA-21 plays an important role in the protection of heart function and is a possible mechanism in ischemic disease. We also reported that overexpression of mi RNA-494 was protective against ischemia/reperfusion-induced cardiac injury. Mi RNA-214 has been demonstrated to be protective for H2O2-induced cardiac myocyte injury. However, it remains unclear that whether mi RNA-214 correlates with sepsis-induced myocardial injury. Given the myocardial injury is the major cause of death in sepsis, we should focus on determining the association between mi RNA-214 expression and sepsis-induced myocardial injury and whether mi RNA-214 has effects on sepsis-induced myocardial injury.Methods:1 Sepsis was induced by cecal ligation and puncture. Then the mice were randomly devided into 6 groups: sham operation group, cecal ligation and puncture group, mi RNA-214 precursor negative conrtol group, mi RNA-214 inhibitor negative control group, mi RNA-214 precusor group, mi RNA-214 inhibitor group. Mice were sacrificed and hearts were removed for determination of mi RNA-214 expression by RT-PCR in Sham and CLP group at 6 h, 12 h, 24 h and in all groups at 12 h.2 Sepsis was induced by cecal ligation and puncture. Then the mice were randomly devided into 4 groups: sham operation group, cecal ligation and puncture group, CLP group with mi RNA-214 precursor treated, CLP group with mi RNA-214 inhibitor treated. Blood samples and the hearts were collected for determination of the BNP, c Tn I and the inflammatory factor concentration in all groups at 12 h and 24 h. And cardiac myocyte apoptosis rate by flow cytometry and pathological transformation by microscopic examination in all groups at 24 h.Results:1 Mi RNA-214 is up-regulated in mouse hearts after sepsisWe found that mi R-214 expression levels were all upregulated at each terminal after CLP. Mi R-214 expression was significantly higher in mouse hearts after sepsis than in sham mice(2.28-fold, P<0.05 at 6 h; 1.89-fold, P<0.05 at 12 h; and 1.53-fold, P<0.05 at 24 h).2 Modμlating mi R-214 expression in mouse heartsMi R-214 precursor increased mi R-214 expression by 1.86-fold and mi R-214 inhibitor decreased by 84.5% in heart tissue compared with CLP mice at 12 h. Mi RNA-214 control had no effects on mi RNA-214 expression.3 Mi RNA-214 had a protective effect against the sepsis induced cardiac injuryCompared with CLP group, the concentration of the serum BNP and c Tn I, tumor necrosis factor-alpha(TNF-α) and the interleukin-6(IL-6) were lower than those in mi R-214 precusor group, the interleukin-10(IL-10) was increased. However, these indicators were just the opposite in anti-mi R-214 group at 12 h and 24 h. Compared with CLP group, the cardiac myocyte apoptosis rate was decreased in mi R-214 precusor group, but increased in mi R-214 inhibitor group at 24 h. The microscopic examination showed that cardiac injury was attenuated in mi R-214 precusor group compared with CLP group.Conclusions:1 Mi RNA-214 expression was upregulated in myocardial injury in CLP mice.2 Mi RNA-214 expression was related to myocardial protection in sepsis. Mi RNA-214 overexpression can decrease myocardial inflammatory response and alleviate sepsis myocardial injury. And it can protect cardiomyocyte apoptosis. |
PDF Full Text Request