Inhibition of septic organ failure by teprenone-induced induction of heat shock protein

本研究旨在探讨戊二酮诱导热休克蛋白（HSP）对全身脏器的影响，以抑制大鼠脓毒性脏器衰竭的诱导。截至1999年，我们发现应用热休克蛋白诱导剂替普龙能诱导肺、肾、肝、肠黏膜和膈膜的热休克蛋白70，并发现替普龙有减轻大鼠脓毒性全身器官衰竭的作用。2000年，我们研究了替普利酮对脓毒症大鼠脓毒症条件下作为脓毒介质的细胞因子的抑制作用。我们还研究了自由基对大鼠膈肌收缩力的影响，自由基在引起脓毒性器官衰竭中起重要作用。结果发现：1)脓毒症所致膈功能障碍是由于脓毒症所致的脓毒症自由基增加所致，2)同样由脓毒症引起的自由基清除剂的增加并不能完全抑制自由基的影响，3)戊二酮诱导的HSP-70的诱导抑制了氧自由基的产生。我们还研究了脓毒症和自由基清除剂对戊巴比妥诱导的大鼠海马皮层EPSPs （fepsp）兴奋性突触传递抑制的影响。我们发现败血症促进戊巴比妥诱导的兴奋性突触传递的抑制，自由基清除剂抑制败血症的影响。

The aim of this study is to evaluate the effect of the teprenone-induced induction of the heat shock protein (HSP) on systemic organs to inhibit induction of the septic organ failure with rats. Up to 1999, we have found that application of teprenone, a HSP inducer, induces HSP-70 in lung, kidney, liver, intestinal mucosa, and diaphragm, and that teprenone has an effect to attenuate septic systemic organ failure in rats. In 2000, we have investigated the effect of teprenone to inhibit increase in cytokines that act as septic mediators under the condition of sepsis in rats. We also investigated the effects of free radicals that play an important role to elicit septic organ failure on diaphragmatic contractility in rats. It is found that 1) the sepsis-induced diaphragmatic dysfunction was elicited by the increased septic free radicals, 2) the increase in free radical scavengers, which is also elicited by sepsis, could not completely suppress the influence of the free radicals, and 3) teprenone-induced induction of HSP-70 inhibits the production of oxygen free radicals. We also investigated the effect of sepsis and free radical scavengers on pentobarbital-induced depression of excitatory synaptic transmissions in rat hippocampal slices with field EPSPs (fEPSPs). We have found that sepsis facilitates the pentobarbital-induced depression of excitatory synaptic transmissions and the free radical scavengers suppress the influences of sepsis.