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

替普瑞酮诱导的热休克蛋白对脓毒症器官衰竭的抑制作用

• 批准号: 10671435
• 负责人: NARIMATSU Eichi
• 金额: $ 2.43万
• 依托单位: Sapporo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671435/
• 关键词: sepsis; Organ failure; heat shock protein; diaphragmatic contractility; oxygen free radicals; free radical scavengers; glutamatergic synaptic transmission; teprenone; 呼吸不全; 多発性壊死性腸炎; 多臓器障害; 横隔膜収縮力; サイトカイン; エンドトキシン; 一酸化チッソ

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.

本研究的目的是评价替普瑞酮诱导的热休克蛋白（HSP）诱导对全身器官的影响，以抑制诱导大鼠脓毒性器官衰竭。直到1999年，我们已经发现，应用替普瑞酮，HSP诱导剂，诱导HSP-70在肺，肾，肝，肠粘膜，和隔膜，和替普瑞酮有效果，以减轻脓毒性全身器官衰竭大鼠。在2000年，我们研究了替普瑞酮对大鼠脓毒症条件下作为脓毒症介质的细胞因子增加的抑制作用。我们还研究了在引起脓毒性器官衰竭中起重要作用的自由基对大鼠血管收缩力的影响。结果发现：1）脓毒症诱导的代谢功能障碍是由脓毒症自由基增加引起的，2）自由基清除剂的增加也是由脓毒症引起的，但不能完全抑制自由基的影响，3）替普瑞酮诱导的HSP-70诱导抑制氧自由基的产生。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脑片兴奋性突触传递抑制的影响。我们已经发现，脓毒症促进戊巴比妥诱导的兴奋性突触传递的抑制和自由基清除剂抑制脓毒症的影响。

项目成果

Nakayama Y: "Propofol enhances a d-tubocurarine-induced t witch depression in septic rat diaphragm"Anesth Analg. 90. 80-84 (2000)

Nakayama Y：“异丙酚增强了败血症大鼠膈肌中 d-筒箭毒碱诱导的抽搐抑制”Anesth Analg。

成松英智: "Sepsis attenuates the intensity of the neuromoscular blocking effect of d-fubocurarine and the antugonistic altian of neost fmine and edrophonian deppression of muscle cntractility of the dyphy" Acta Anesthetica Scandinavia. 43・2. 196-201 (1999)

Hidetomo Narimatsu：“脓毒症减弱了 d-fubocurarine 和 Neost fmine 的拮抗剂 altian 和 dyphy 肌肉收缩性的 edrophonian 抑制作用的强度”Acta Anesthetica Scandinavia 43·2 (1999)。

Tohdoh Y: "Involvement of adenosine neuromodulation in pentobarbital-induced field EPSP depression in rat hippocampal slices."Anesth Analg. 91. 1537-1541 (2000)

Tohdoh Y：“腺苷神经调节参与戊巴比妥诱导的大鼠海马切片中的场 EPSP 抑制。”Anesth Analg。

住田臣造: "敗血症と熱ショック蛋白質" Shock(日本Shock学会雑誌). 13・2. 40-44 (1998)

Shinzo Sumita：“败血症和热休克蛋白”休克（日本休克学会杂志）13・2（1998）。

Fujimura N: "Effects of free radical scavengers on diaphragmatic contractility in septic peritonitis"Am J Respir Crit Care Med. 162. 2159-2165 (2000)

Fujimura N：“自由基清除剂对化脓性腹膜炎膈肌收缩力的影响”Am J Respir Crit Care Med。