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    Please use this identifier to cite or link to this item: http://ir.cnu.edu.tw/handle/310902800/28573

    標題: Exogenous Heat Shock Cognate Protein 70 Pretreatment Attenuates Cardiac And Hepatic Dysfunction With Associated Anti-Inflammatory Responses In Experimental Septic Shock
    作者: Hsu, Jong-Hau
    Yang, Rei-Cheng
    Lin, Shih-Jen
    Liou, Shu-Fen
    Dai, Zen-Kong
    Yeh, Jwu-Lai
    Wu, Jiunn-Ren
    貢獻者: 藥學系
    關鍵字: Heat shock protein
    日期: 2014-12
    上傳時間: 2015-05-06 21:21:10 (UTC+8)
    出版者: Lippincott Williams & Wilkins
    摘要: It has been recently demonstrated that intracellular heat shock cognate protein 70 (HSC70) can be released into extracellular space with physiologic effects. However, its extracellular function in sepsis is not clear. In this study, we hypothesize that extracellular HSC70 can protect against lipopolysaccharide (LPS)-induced myocardial and hepatic dysfunction because of its anti-inflammatory actions. In Wistar rats, septic shock developed with hypotension, tachycardia, and myocardial and hepatic dysfunction at 4 h following LPS administration (10 mg/kg, i.v.). Pretreatment with recombinant bovine HSC70 (20 mu g/kg, i.v.) attenuated LPS-induced hypotension and tachycardia by 21% and 23%, respectively (P < 0.05), improved myocardial dysfunction (left ventricular systolic pressure: 33%; max dP/dt: 20%; min dP/dt: 33%, P < 0.05), and prevented hepatic dysfunction (glutamic-oxaloacetic transaminase: 81 vs. 593 IU/L; glutamic-pyruvic transaminase: 15 vs. 136 IU/L, P G 0.05) compared with LPS-treated rats at 4 h. Heat shock cognate protein 70 also prevented LPS-induced hypoglycemia (217 vs. 59 mg/dL, P G 0.05) and elevated lactate dehydrogenase (1,312 vs. 6,301 IU/L, P G 0.05). Furthermore, HSC70 decreased LPS-induced elevation of circulating tumor necrosis factor alpha and nitrite/nitrate, and tissue expression of inducible nitric oxide synthase, cyclooxygenase 2, and matrix metalloproteinase 9 in the heart and liver. To investigate underlying mechanisms, we found that HSC70 attenuated LPS-induced nuclear translocation of nuclear factor kappa B subunit p65 by blocking the phosphorylation of inhibitor of nuclear factor kappa B. Finally, we showed that HSC70 repressed the activation of MAPKs caused by LPS. These results demonstrate that in LPS-induced septic shock, extracellular HSC70 conveys pleiotropic protection on myocardial, hepatic, and systemic derangements, with associated inhibition of proinflammatory mediators including tumor necrosis factor alpha, nitric oxide, cyclooxygenase 2, and matrix metalloproteinase 9, through mitogen-activated protein kinase/nuclear factor kappa B signaling pathways. Therefore, extracellular HSC70 may have a promising role in the prophylactic treatment of sepsis.
    關聯: Shock, v.42 n.6, pp.540-547
    Appears in Collections:[藥學系(所)] 期刊論文

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