實驗室分機 請向系上詢問 實驗室位置 第一醫學大樓 5 樓 麻醉部主治醫師兼麻醉部恢復室主任 Head at Post-anesthetic Unit, Department of Anesthesiology

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1 麻醉 科 師資陣容 余黃平 English Name 職稱 Title 畢業學校 School 學位 Degree 畢業年次 Year of graduation 研究領域 實驗室分機 請向系上詢問 實驗室位置 第一醫學大樓 5 樓 Yu Huang Ping 麻醉部主治醫師兼麻醉部恢復室主任 Head at Post-anesthetic Unit, Department of Anesthesiology 一 長庚大學 一 Chang Gung University 一 醫學博士 一 PhD 一 95 年 一 2006 重症醫學 分子生物學

2 Research Topic The mission of our lab is to foster research and instruction in the areas of trauma, hemorrhage, sepsis, and surgical critical care and to translate these experimental studies to the bedside using novel treatment modalities so that complications and mortality rates in such trauma patients can be decreased. Profound suppression of cardiovascular functions occurs following soft tissue injury and major blood loss. Our results indicate that proestrus female rodents have maintained cardiovascular responses after trauma as opposed to the markedly decreased responses in males under those conditions. The advantage the proestrus females have in tolerating trauma disappears following ovariectomy/aging. Treatment of mice or rats after trauma with flutamide is also effective in restoring the cardiovascular functions and decreasing mortality rates from subsequent sepsis. In addition to the known effects of flutamide, i.e., androgen receptor antagonism, the salutary effects of flutamide on cardiac functions are mediated via E2-dependent pathway through estrogen receptor (ER)-α, and ER-β upregulation of peroxisome proliferator-activated receptor coactivator-1 (PGC-1). Administration of female sex hormones prevents the depression in cardiovascular responses following trauma in males and ovariectomized females. Studies also indicate that the salutary effects of E2 on cardiac function are mediated via ER-β and ER-β-induced upregulation of Heat shock proteins likely plays a significant role in the E2-mediated cardioprotection following trauma. Administration of ER- agonist diarylpropionitrile (DPN) itself appears to be a novel adjunct for restoring cardiac function following trauma. Alternatively, ER- agonist (propyl pyrazole triol, PPT) improved hepatic functions after trauma. Furthermore, the salutary effects of E2 on tissue neutrophil sequestration following trauma are ER subtype and tissue specific. In addition to the genomic, E2 also mediates its salutary effects on cardiac function by the non-genomic pathway. Thus, alteration or modulation of the prevailing hormone milieu at the time of injury appears to be a novel therapeutic agent for improving outcome after injury. 近五年發表 1. Yu HP, Yang S, Choudhry MA, Hsieh YC, Bland KI, Chaudry IH. (2005) Mechanism responsible for the salutary effects of flutamide on cardiac performance after trauma-hemorrhagic shock: Upregulation of cardiomyocyte estrogen receptor. Surgery 138: (SCI, Impact factor 3.389) 2. Hsieh YC, Yang S, Choudhry MA, Yu HP, Rue LW III, Bland KI, Chaudry IH. (2005) PGC-1 upregulation via estrogen receptors: a common mechanism of salutary effects of estrogen and flutamide on heart function after trauma-hemorrhage. Am J Physiol Heart Circ Physiol 289: H2665-H2672. (SCI, Impact factor 3.643) 3. Yu HP, Shimizu T, Choudhry MA, Hsieh YC, Suzuki T, Bland KI, Chaudry IH. (2006) Mechanism of cardioprotection following trauma-hemorrhagic

3 shock by a selective estrogen receptor-β agonist: Up-regulation of cardiac heat shock factor-1 and heat shock proteins. J Mol Cell Cardiol 40: (SCI, Impact factor 5.054) 4. Yu HP, Choudhry MA, Shimizu T, Hsieh YC, Schwacha MG, Yang S, Chaudry IH. (2006) Mechanism of the salutary effects of Flutamide on intestinal myeloperoxidase activity following trauma-hemorrhage: Upregulation of estrogen receptor-β-dependent HO-1. J Leukoc Biol 79: (SCI, Impact factor 4.605) 5. Yu HP, Lui PW, Hwang TL, Yen CH, Lau YT. (2006) Propofol improves endothelial function and attenuates vascular superoxide production in septic rats. Crit Care Med 34: (SCI, Impact factor 6.594) 6. Yu HP, Shimizu T, Hsieh YC, Suzuki T, Choudhry MA, Schwacha MG, Chaudry IH. (2006) Tissue-specific expression of estrogen receptors and their roles in the regulation of neutrophil infiltration in various organs following trauma-hemorrhae. J Leukoc Biol 79: (SCI, Impact factor 4.605) 7. Yu HP, Hsieh YC, Suzuki T, Shimizu T, Choudhry MA, Schwacha MG, Chaudry IH. (2006) Salutary effects of estrogen receptor-β agonist on lung injury following trauma-hemorrhage. Am J Physiol Lung Cell Mol Physiol 290: L1004-L1009. (SCI, Impact factor 3.924) 8. Yu HP, Yang S, Hsieh YC, Choudhry MA, Bland KI, Chaudry IH. (2006) Maintenance of lung myeloperoxidase activity in proestrus females following trauma-hemorrhage: upregulation of hemeoxygenase-1. Am J Physiol Lung Cell Mol Physiol 291: L400-L406. (SCI, Impact factor 3.924) 9. Hsieh YC, Choudhry MA, Yu HP, Shimizu T, Yang S, Suzuki T, Chen J, Bland KI, Chaudry IH. (2006) Inhibition of cardiac PGC-1 alpha expression abolishes ERbeta agonist-mediated cardioprotection following trauma-hemorrhage. FASEB J 20: (SCI, Impact factor 7.049) 10. Szalay L, Shimizu T, Suzuki T, Yu HP, Choudhry MA, Schwacha MG, Rue LW III, Bland KI, Chaudry IH. (2006) Estradiol improves cardiac and hepatic function after trauma-hemorrhage: role of enhanced heat shock protein expression. Am J Physiol Regul Integr Comp Physiol 290: R812-R818. (SCI, Impact factor 3.272) 11. Hsieh YC, Yang S, Choudhry MA, Yu HP, Rue LW III, Bland KI, Chaudry IH (2006). Flutamide restores cardiac function after trauma-hemorrhage via an estrogen-dependent pathway through upregulation of PGC-1. Am J Physiol Heart Circ Physiol 290: H416-H423. (SCI, Impact factor 3.643) 12. Suzuki T, Shimizu T, Yu HP, Hsieh YC, Choudhry MA, Bland KI, Chaudry IH. (2006) 17β-estradiol administration following trauma-hemorrhage prevents the increase in kupffer vell cytokine release and MAPK activation predominantly via estrogen receptor-α. Surgery 140: (SCI, Impact factor 3.389) 13. Hsieh YC, Yu HP, Suzuki T, Choudhry MA, Schwacha MG, Bland KI, Chaudry IH. (2006) Upregulation of mitochondrial respiratory complex IV by estrogen receptor-beta is critical for inhibiting mitochondrial apoptotic signaling and restoring cardiac functions following trauma-hemorrhage. J

4 Mol Cell Cardiol 41: (SCI, Impact factor 5.054) 14. Yu HP, Hsieh YC, Suzuki T, Choudhry MA, Schwacha MG, Bland KI, Chaudry IH. (2007) The PI3K/Akt Pathway Mediates the Non-Genomic Cardioprotective Effects of Estrogen Following Trauma-Hemorrhage Ann Surg 245: (SCI, Impact factor 8.46) 15. Suzuki T, Shimizu T, Yu HP, Hsieh YC, Choudhry MA, Schwacha MG, Chaudry IH. (2007) Tissue compartment-specific role of estrogen receptor subtypes in immune cell cytokine production following trauma-hemorrhage. J Appl Physiol 102: (SCI, Impact 3.658) 16. Shimizu T, Yu HP, Hsieh YC, Choudhry MA, Suzuki T, Bland KI, Caudry IH. (2007) Flutamide Attenuates Pro-inflammatory Cytokine Production and Hepatic Injury Following Trauma-Hemorrhage via Estrogen Receptor-related Pathway. Ann Surg 245: (SCI, Impact factor 8.46) 17. Shimizu T, Yu HP, Hsieh YC, Choudhry MA, Bland KI, Chaudry IH. (2007) The role of estrogen receptor subtypes in ameliorating hepatic injury following trauma-hemorrhage. J Hepatol 46: (SCI, Impact factor 7.056) 18. Hsieh YC, Yu HP, Suzuki T, Choudhry MA, Schwacha MG, Chaudry IH. (2007) GPR30-dependent PKA pathway is critical in non-genomic effects of estrogen in attenuating liver injury following trauma-hemorrhage. Am J Pathol 170: (SCI, Impact factor 5.697) 19. Suzuki T, Shimizu T, Yu HP, Hsieh YC, Choudhry MA, Chaudry IH. (2007) Salutary effects of 17β-estradiol on T cell signaling and cytokine production after trauma-hemorrhage are mediated primarily via estrogen receptor-α. Am J Physiol Cell Physiol 292: C2103-C2111. (SCI, Impact factor 4.23) 20. Suzuki T, Shimizu T, Yu HP, Hsieh YC, Choudhry MA, Bland KI, Chaudry IH. (2007) Estrogen receptor-α predominately mediates the salutary effects of 17β-estradiol on splenic macrophages following trauma-hemorrhage. Am J Physiol Cell Physiol 293: C978-C984. (SCI, Impact factor 4.23) 21. Yu HP, Hsieh YC, Suzuki T, Choudhry MA, Schwacha MG, Bland KI, Chaudry IH. (2007) Mechanism of the nongenomic effects of estrogen on intestinal myeloperoxidase activity following trauma-hemorrhage: up-regulation of the PI3K/Akt pathway. J Leukoc Biol 82: (SCI, Impact factor 4.605) 22. Suzuki T, Yu HP, Hsieh YC, Choudhry MA, Bland KI, Chaudry IH. (2008) Estrogen-mediated activation of non-genomic pathway improves macrophages cytokine production following trauma-hemorrhage. J Cell Physiol 214: (SCI, Impact factor 4.313) 23. Suzuki T, Yu HP, Hsieh YC, Choudhry MA, Bland KI, Chaudry IH. (2008) Mitogen activated protein kinase (MAPK) mediates non-genomic pathway of estrogen on T cell cytokine production following trauma-hemorrhage. Cytokine 42: (SCI, Impact factor 2.214) 24. Yu HP, Lau YT. (2008) Since when did sedatives start to save lives? Crit Care Med 36: (SCI, Impact factor 6.594)

5 25. Shimizu T, Suzuki T, Yu HP, Yokoyama Y, Choudhry MA, Bland KI, Chaudry IH. (2008) The role of estrogen receptor subtypes on hepatic neutrophil accumulation following trauma-hemorrhage: direct modulation of CINC-1 production by Kupffer cells. Cytokine 43: (SCI, Impact factor 2.214) 26. Su BC, Yu HP, Yang MW, Lin CC, Kao MC, Chang CH, Lee WC. (2008) Reliability of a new ultrasonic cardiac output monitor in recipients of living donor liver transplantation. Liver Transpl 14: (SCI, Impact factor 4.085) 27. Liu FC, Day YJ, Liou JT, Lau YT, Yu HP*. (2008) Sirtinol attenuates hepatic injury and pro-inflammatory cytokine production following trauma-hemorrhage in male Sprague-Dawley rats. Acta Anaesthesiol Scand 52: (SCI, Impact factor 1.953) (Corresponding author) 28. Yu HP, Hsu JC, Yen CH, Ma YH, Lau YT. (2008) Hyporeactivity of renal artery to angiotensin II in septic rats. Chinese J Physiol 51: (SCI, Impact factor 0.655) 29. Wu CT, Yu HP, Chung CY, Lau YT, Liao SK. (2008) Resveratrol attenuates lung inflammation and pro-inflammatory cytokine production following trauma-hemorrhage. Chinese J Physiol 51: (SCI, Impact factor 0.655) 30. Yu HP, Hsu JC, Hwang TL, Yen CH, Lau YT. (2008) Resveratrol attenuates hepatic injury after trauma-hemorrhage via estrogen-related pathway. Shock 30: (SCI, Impact factor 3.394) 31. Yu HP, Chaudry IH. (2009) The role of estrogen and receptor agonists in maintaining organ function following trauma-hemorrhage. Shock 31: (SCI, Impact factor 3.394) 32. Liu FC, Day YJ, Liao CH, Liou JT, Mao CC, Yu HP*. (2009) Hemeoxygenase-1 upregulation is critical for sirtinol-mediated attenuation of lung injury after trauma-hemorrhage in a rodent model. Anesth Analg 108: (SCI, Impact factor 2.59) (Corresponding author) 33. Yu HP, Hsieh PW, Chang YJ, Chung PJ, Kuo LM, Hwang TL. (2009) DSM-RX78, a new phosphodiesterase inhibitor, suppresses superoxide anion production in activated human neutrophils and attenuates hemorrhagic shock-induced lung injury in rats. BIOCHEMICAL PHARMACOLOGY in press. (SCI, Impact factor 4.838) 34. Yu HP, Hwang TL, Hwang TL, Yen CH, Lau YT. (2010) Resveratrol prevents endothelial dysfunction and aortic superoxide production after trauma hemorrhage through estrogen receptor-dependent hemeoxygenase-1 pathway. Crit Care Med in press. (SCI, Impact factor 6.594) 35. Yu HP, Yang SC, Lau YT, Hwang TL. (2010) Role of Akt-dependent up-regulation of hemeoxygenase-1 in resveratrol-mediated attenuation of hepatic injury after trauma-hemorrhage. Surgery in press. (SCI, Impact factor 3.389)

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