The effect of TNF-α in intracellular Ca2+-overload associated cardiac dysfunction / 临床儿科杂志

ABSTRACT

Objective To explore the effect of TNF-α in intracellular Ca~(2+)-overload associated myocardial injury. Methods Thirty Wistar rats were randomly divided into three groupscontrol group,Ca~(2+)+-paradox group,and pentoxifylline treatment group. The intracellular Ca~(2+)-overload rat model was established by pre-filling the rats with Langendorff for 20 minutes,isolated rat hearts subjected to Ca~(2+)-depletion for 5 minutes and Ca~(2+)-repletion for 30 minites(Ca~(2+)-paradox). Changes in hemodynamics indexes were monitored continuously. TNF-α in cardiac tissues was tested by ELISA method,and nuclear factor-κB(NF-κB)in cardiac tissues was detected with Western blot. Results Dramatic depression in left ventricle contraction function was found in the Ca~(2+)-paradox heartssignificant decrease in left ventricular diastolic pressure(LVDP),markedly elevated left ventricular end diastolic pressure(LVEDP),decreased dP/dt ratio,increased TNF-α content,decreased cytosolic/homogenate NF-κB ratio. All these changes in Ca~(2+)-paradox group were significantly attenuated upon the treatment with 100 μmol/L pentoxifylline. Conclusions Activation of NF-κB and increased production of TNF-α may play important roles in cardiac injury associated with intracellular Ca~(2+)-overload.