Yang R C, Wang C I, Chen H W, Chou F P, Lue S I, Hwang K P
Department of Physiology, Graduate Institute of Medicine, Kaohsiung Medical College, Kaohsiung City, Taiwan, Republic of China.
Kaohsiung J Med Sci. 1998 Nov;14(11):664-72.
Sepsis is an increasingly common and lethal diagnosis in hospitalized patients. In spite of the advances in antibiotics and medical equipment, the mortality rate has not been improved in the last decade. Recently, heat shock proteins (Hsps) have been well documented to play a self-protective role in almost all living cells under various pathological and physiological stresses through a mechanism known as thermotolerance or cross tolerance. The present study was designed to investigate the expression of Hsp72 and the protective role of pre-induction of Hsps in the mortality during different phases of sepsis. Adult male Sprague-Dawley rats were employed in the study. Sepsis was induced by cecal ligation and puncture (CLP). Heat shock treatment was performed 16 hrs before sepsis induction by heating the rats whole-bodily with an electric heating pad under general anesthesia. The mortality rates with time in both control and preheated groups were monitored. Hsp72 was detected by SDS-PAGE, Western blotting and immunostaining in the brain, heart, liver, kidney, lung, adrenal gland, muscle and lymphocytes. The results show that both early (9 hrs post-CLP) and late (18 hrs post-CLP) sepsis failed to increase the synthesis of Hsp72. Previous induction of Hsps by heat shock treatment significantly decreased the mortality rate of late sepsis. Applying a sufficient inducer to lymphocytes of late sepsis reversed the synthesis of Hsp72 from inactive state into an over-expressive situation in vitro. These results suggest that Hsps are involved in the pathogenesis of sepsis and the involvement of Hsps during the progression of sepsis could add to a first line of host defense against invasive pathogens. Searching for an acceptable agent or less invasive method that leads to increased Hsps expression may provide a means for better treatment of severe infection.
脓毒症是住院患者中越来越常见且致命的诊断。尽管抗生素和医疗设备有所进步，但过去十年死亡率并未得到改善。最近，热休克蛋白（Hsps）已被充分证明在各种病理和生理应激下，通过一种称为热耐受或交叉耐受的机制，在几乎所有活细胞中发挥自我保护作用。本研究旨在调查Hsp72的表达以及热休克蛋白预诱导在脓毒症不同阶段死亡率中的保护作用。本研究采用成年雄性Sprague-Dawley大鼠。通过盲肠结扎和穿刺（CLP）诱导脓毒症。在全身麻醉下，使用电加热垫对大鼠进行全身加热，在诱导脓毒症前16小时进行热休克处理。监测对照组和预热组随时间的死亡率。通过SDS-PAGE、蛋白质印迹法和免疫染色检测脑、心脏、肝脏、肾脏、肺、肾上腺、肌肉和淋巴细胞中的Hsp72。结果表明，早期（CLP后9小时）和晚期（CLP后18小时）脓毒症均未能增加Hsp72的合成。热休克处理预先诱导热休克蛋白可显著降低晚期脓毒症的死亡率。在体外，对晚期脓毒症淋巴细胞应用足够的诱导剂可使Hsp72的合成从无活性状态转变为过度表达状态。这些结果表明，热休克蛋白参与脓毒症的发病机制，并且在脓毒症进展过程中热休克蛋白的参与可能会增强宿主抵御侵袭性病原体的第一道防线。寻找一种可接受的药物或侵入性较小的方法来增加热休克蛋白的表达，可能为更好地治疗严重感染提供一种手段。
