Attenuation of sepsis induced apoptosis by heat shock pretreatment in rats

Apoptosis is a process by which cells undergo a form of non-necrotic cellul ar suicide. Although it is a programmed process, apoptosis can be induced b y various stressors. During sepsis, apoptosis has been regarded as an impor tant cause of cell death in the immune system, leading to unresponsiveness to treatment. This study was designed to investigate how prior heat shock i nduction can influence the rate of apoptosis in animals that have experienc ed sepsis. Sprague-Dawley rats were used, and experimental sepsis was induc ed by cecal ligation and puncture (CLP). Animals in the heated group were a nesthetized and received heat shock by whole-body hyperthermia. They were s acrificed 9 h and 18 h after CLP as early and late sepsis, respectively. Ap optosis was evaluated by "DNA ladder" detection in agarose electrophoresis and Tdt-mediated dUTP nick end-labeling (TUNEL) assay. Hsp72 was detected b y Western blot analysis. The results showed that the DNA ladder was detecte d most clearly in the thymus at the late phase of sepsis with time course d ependence, while it showed less clearly in heat shock treated animals. Hist opathological study by TUNEL assay obtained similar results in the thymus, where the cortex was more susceptible to apoptosis than the medulla. The We stern blot analysis showed that the heat shock induced Hsp72 concomitant wi th an increase in Bcl-2:Bax ratio. In conclusion, heat shock pretreatment p revents rats from sepsis-induced apoptosis that may account for the better outcome of experimental sepsis. An increase in the Bcl-2:Bax ratio may in p art explain the molecular mechanism of the effect of heat shock pretreatmen t.