聯絡電話
蔡靜宜
副教授
中樞心血管調控
訊息傳遞
分子影像
殺蟲劑、麻醉劑之藥理學
氧化還原訊息與氧化壓力
- 電子郵件信箱
cytsai@cgmh.org.tw
研究簡介
研究主軸: 解開腦幹調節心血管功能在健康和疾病模型中的細胞和分子機制
本實驗室的研究聚焦於腦幹死亡 (brainstem death)，神經源性高血壓 (neurogenic hypertension) 和肝性腦病變 (hepatic encephalopathy) 等疾病模式腦幹心血管調控中所涉及的訊息傳遞路徑和神經迴路探討。我們的研究是使用臨床相關的動物模型，並將細胞和分子生物學整合到系統生理學中來進行。近年來，我們亦將腦幹心血管調節的研究視野擴展到感壓反射神經迴路中所涉及到的腦幹核區之間功能性連結的圖像變化，並表明這些變化具有生理學和病理學上的意義。
1. 提出延腦腹外側核 (RVLM) 在有機磷美文松中毒引起的腦幹死亡模型中的細胞分子機制。
我們的研究發現RVLM內PI3K/Akt訊息路徑活化會導致NF-κB/NOS II/peroxynitrite路徑進一步活化並造成腦幹心血管調控失能。FLJ10540為PI3K結合蛋白，可以促進PI3K/Akt訊息傳遞路徑引起心血管調控失能。另一方面，PTEN可以透過減少本身的氧化態來增進活性，並扮演PI3K/Akt訊息路徑的負調控者來抑制下游的NOS II/peroxynitrite路徑，進而減緩心血管調控失能。(Biochem Pharmacol. 2018 Sep; 155:207-212.)
2. 我們還將分子影像與腦幹心血管調節的生理評估相結合，使用磁振擴散張量影像 (DTI) 來檢測感壓反射神經迴路中涉及的腦幹核區之間的功能性連結變化。
在病理生理條件下 (例如神經源性高血壓)，此神經迴路連結中斷，產生高血壓。當神經連結中斷可逆轉，血壓回復正常值，代表此疾病模式可以被治療。然而，當病理生理狀況演變為病理狀態時 (例如肝性腦病變)，此神經連結中斷不可逆轉，最後動物死亡，代表此疾病模式不可以被治療。(J Physiol. 2019 Jan; 597(1):41-55.)
學術著作
Recent publications (Pubmed Search)
1: Hung YY, Tsai CY, Lee CT, Fu HC, Chou CK, Yang YC, Chen JF, Kang HY. Targeting TNIP1 as a new therapeutic avenue for major depressive disorder. Brain Behav Immun. 2025 May;126:214-224. doi: 10.1016/j.bbi.2025.02.015. Epub 2025 Feb 18. PMID: 39978697.
2: Yu HR, Tsai CY, Chen WL, Liu PY, Tain YL, Sheen JM, Huang YS, Tiao MM, Chiu CY. Exploring Oxidative Stress and Metabolic Dysregulation in Lung Tissues of Offspring Rats Exposed to Prenatal Polystyrene Microplastics: Effects of Melatonin Treatment. Antioxidants (Basel). 2024 Nov 28;13(12):1459. doi: 10.3390/antiox13121459. PMID: 39765788; PMCID: PMC11672973.
3: Tsai CY, Lee CL, Wu JCC. Astrocyte-secreted lipocalin-2 elicits bioenergetic failure-induced neuronal death that is causally related to high fatality in a mouse model of hepatic encephalopathy. Neurochem Int. 2024 Sep;178:105800. doi: 10.1016/j.neuint.2024.105800. Epub 2024 Jul 2. PMID: 38964718.
4: Thangudu S, Tsai CY, Lin WC, Su CH. Modified gefitinib conjugated Fe3O4 NPs for improved delivery of chemo drugs following an image-guided mechanistic study of inner vs. outer tumor uptake for the treatment of non-small cell lung cancer. Front Bioeng Biotechnol. 2023 Oct 9;11:1272492. doi: 10.3389/fbioe.2023.1272492. PMID: 37877039; PMCID: PMC10591449.
5: Tsai CY, Wu JCC, Wu CJ, Chan SHH. Protective role of VEGF/VEGFR2 signaling against high fatality associated with hepatic encephalopathy via sustaining mitochondrial bioenergetics functions. J Biomed Sci. 2022 Jul 3;29(1):47. doi: 10.1186/s12929-022-00831-0. PMID: 35786324; PMCID: PMC9251935.
6: Tsai CY, Fang C, Wu JCC, Wu CJ, Dai KY, Chen SM. Neuroinflammation and Microglial Activation at Rostral Ventrolateral Medulla Underpin Cadmium-Induced Cardiovascular Dysregulation in Rats. J Inflamm Res. 2021 Aug 11;14:3863-3877. doi: 10.2147/JIR.S325528. PMID: 34408468; PMCID: PMC8364915.
7: Poon YY, Liu YW, Huang YH, Chan SHH, Tsai CY. Postoperative Stroke after Spinal Anesthesia and Responses of Carotid or Cerebral Blood Flow and Baroreflex Functionality to Spinal Bupivacaine in Rats. Biology (Basel). 2021 Jul 2;10(7):617. doi: 10.3390/biology10070617. PMID: 34356472; PMCID: PMC8301092.
8: Poon YY, Tsai CY, Huang YH, Wu JCC, Chan SHH, Chan JYH. Disproportional cardiovascular depressive effects of isoflurane: Serendipitous findings from a comprehensive re-visit in mice. Lab Anim (NY). 2021 Jan;50(1):26-31. doi: 10.1038/s41684-020-00684-w. Epub 2020 Nov 30. PMID: 33257894.
9: Tsai CY, Wu CJ, Wu JCC, Fang C, Huang YH, Dai KY. Redox-active DJ-1 sustains brainstem cardiovascular regulation via maintenance of mitochondrial function during mevinphos intoxication. Neurochem Int. 2020 Oct;139:104791. doi: 10.1016/j.neuint.2020.104791. Epub 2020 Jul 8. PMID: 32650030.
10: Tsai CY, Wu JCC, Chen SM, Lin HH, Chan JYH, Chan SHH. Physiological and pathophysiological evaluation of baroreflex functionality with concurrent diffusion tensor imaging of its neural circuit in the rat. Biomed J. 2019 Dec;42(6):381-393. doi: 10.1016/j.bj.2019.10.006. Epub 2019 Dec 24. PMID: 31948602; PMCID: PMC6962742.
11: Chen SM, Phuagkhaopong S, Fang C, Wu JCC, Huang YH, Vivithanaporn P, Lin HH, Tsai CY. Dose-Dependent Acute Circulatory Fates Elicited by Cadmium Are Mediated by Differential Engagements of Cardiovascular Regulatory Mechanisms in Brain. Front Physiol. 2019 Jun 18;10:772. doi: 10.3389/fphys.2019.00772. PMID: 31275174; PMCID: PMC6591476.
12: Mukda S, Tsai CY, Leu S, Yang JL, Chan SHH. Pinin protects astrocytes from cell death after acute ischemic stroke via maintenance of mitochondrial anti-apoptotic and bioenergetics functions. J Biomed Sci. 2019 Jun 5;26(1):43. doi: 10.1186/s12929-019-0538-5. PMID: 31167655; PMCID: PMC6549339.
13: Tsai CY, Poon YY, Huang YH, Chan SH. Activation of spinal nociceptin receptors induces cardiovascular depression and antinociception in an independent manner in mice. J Pain Res. 2018 Nov 1;11:2699-2708. doi: 10.2147/JPR.S175259. PMID: 30464587; PMCID: PMC6219425.
14: Tsai CY, Poon YY, Chan JYH, Chan SHH. Baroreflex functionality in the eye of diffusion tensor imaging. J Physiol. 2019 Jan;597(1):41-55. doi: 10.1113/JP277008. Epub 2018 Nov 2. PMID: 30325020; PMCID: PMC6312450.
15: Tsai CY, Dai KY, Fang C, Wu JCC, Chan SHH. PTEN/FLJ10540/PI3K/Akt cascade in experimental brain stem death: A newfound role for a classical tumorigenic signaling pathway. Biochem Pharmacol. 2018 Sep;155:207-212. doi: 10.1016/j.bcp.2018.07.002. Epub 2018 Jul 3. PMID: 30008438.
16: Tsai CY, Poon YY, Chen CH, Chan SHH. Anomalous baroreflex functionality inherent in floxed and Cre-Lox mice: an overlooked physiological phenotype. Am J Physiol Heart Circ Physiol. 2017 Oct 1;313(4):H700-H707. doi: 10.1152/ajpheart.00346.2017. Epub 2017 Aug 4. PMID: 28778914.
17: Tsai CY, Wu JCC, Fang C, Chang AYW. PTEN, a negative regulator of PI3K/Akt signaling, sustains brain stem cardiovascular regulation during mevinphos intoxication. Neuropharmacology. 2017 Sep 1;123:175-185. doi: 10.1016/j.neuropharm.2017.06.007. Epub 2017 Jun 7. PMID: 28601397.
18: Tsai CY, Su CH, Chan JY, Chan SH. Nitrosative Stress-Induced Disruption of Baroreflex Neural Circuits in a Rat Model of Hepatic Encephalopathy: A DTI Study. Sci Rep. 2017 Jan 12;7:40111. doi: 10.1038/srep40111. PMID: 28079146; PMCID: PMC5228038.
19: Tsai CY, Li FC, Wu CH, Chang AY, Chan SH. Sumoylation of IkB attenuates NF-kB-induced nitrosative stress at rostral entrolateral medulla and cardiovascular depression in experimental brain death. J Biomed Sci. 2016 Sep 22;23(1):65. doi: 10.1186/s12929-016-0283-y. PMID: 27658615; PMCID: PMC5034413.
20: Poon YY, Tsai CY, Cheng CD, Chang AY, Chan SH. Endogenous nitric oxide derived from NOS I or II in thoracic spinal cord exerts opposing tonic modulation on sympathetic vasomotor tone via disparate mechanisms in anesthetized rats. Am J Physiol Heart Circ Physiol. 2016 Sep 1;311(3):H555-62. doi: 10.1152/ajpheart.00246.2016. Epub 2016 Jul 1. PMID: 27371683.
21: Su CH, Tsai CY, Chang AY, Chan JY, Chan SH. MRI/DTI of the Brain Stem Reveals Reversible and Irreversible Disruption of the Baroreflex Neural Circuits: Clinical Implications. Theranostics. 2016 Apr 11;6(6):837-48. doi: 10.7150/thno.14837. PMID: 27162554; PMCID: PMC4860892.
22: Su CH, Tsai CY, Tomanek B, Chen WY, Cheng FY. Evaluation of blood-brain barrier-stealth nanocomposites for in situ glioblastoma theranostics applications. Nanoscale. 2016 Apr 21;8(15):7866-70. doi: 10.1039/c6nr00280c. PMID: 27035391.
23: Hsieh MC, Tsai CY, Liao MC, Yang JL, Su CH, Chen JH. Quantitative Susceptibility Mapping-Based Microscopy of Magnetic Resonance Venography (QSM-mMRV) for In Vivo Morphologically and Functionally Assessing Cerebromicrovasculature in Rat Stroke Model. PLoS One. 2016 Mar 14;11(3):e0149602. doi: 10.1371/journal.pone.0149602. PMID: 26974842; PMCID:
PMC4790912.
24: Tsai CY, Su CH, Leu S, Chang AY, Chan JY, Chan SH. Endogenous vascular endothelial growth factor produces tonic facilitation of cardiac vagal baroreflex via fetal liver kinase-1 in medulla oblongata. Int J Cardiol. 2015;187:421-5. doi: 10.1016/j.ijcard.2015.03.375. Epub 2015 Mar 27. PMID: 25841140.
25: Tsai CY, Chen CH, Chang AY, Chan JY, Chan SH. Upregulation of FLJ10540, a PI3K-association protein, in rostral ventrolateral medulla impairs brain stem cardiovascular regulation during mevinphos intoxication. Biochem Pharmacol. 2015 Jan 1;93(1):34-41. doi: 10.1016/j.bcp.2014.10.018. Epub 2014 Nov 7. PMID: 25449601.
26: Tsai CY, Chua S, Leu S, Chang AY, Chan JY, Chan SH. VEGF tonically sustains myocardial performance via fetal liver kinase-1 in the heart. Int J Cardiol. 2014 Dec 15;177(2):727-30. doi: 10.1016/j.ijcard.2014.10.019. PMID: 25456694.
27: Tsai CY, Chang AY, Chan JY, Chan SH. Activation of PI3K/Akt signaling in rostral ventrolateral medulla impairs brain stem cardiovascular regulation that underpins circulatory depression during mevinphos intoxication. Biochem Pharmacol. 2014 Mar 1;88(1):75-85. doi: 10.1016/j.bcp.2014.01.014. Epub 2014 Jan 22. PMID: 24462917.
28: Tsai CY, Su CH, Baudrie V, Laude D, Weng JC, Chang AY, Chan JY, Elghozi JL, Chan SH. Visualizing oxidative stress-induced depression of cardiac vagal baroreflex by MRI/DTI in a mouse neurogenic hypertension model. Neuroimage. 2013 Nov 15;82:190-9. doi: 10.1016/j.neuroimage.2013.05.124. Epub 2013 Jun 6. PMID: 23747290.
29: Tsai CY, Chan JY, Hsu KS, Chang AY, Chan SH. Brain-derived neurotrophic factor ameliorates brain stem cardiovascular dysregulation during experimental temporal lobe status epilepticus. PLoS One. 2012;7(3):e33527. doi: 10.1371/journal.pone.0033527. Epub 2012 Mar 19. PMID: 22442695; PMCID: PMC3307740.
30: Chan JY, Tsai CY, Wu CH, Li FC, Dai KY, Sun EY, Chan SH, Chang AY. Sumoylation of hypoxia-inducible factor-1α ameliorates failure of brain stem cardiovascular regulation in experimental brain death. PLoS One. 2011 Mar 3;6(3):e17375. doi: 10.1371/journal.pone.0017375. PMID: 21390240; PMCID: PMC3048406.
31: Chou JL, Wu CH, Tsai CY, Chang AY, Chan SH. Proteomic investigation of a neural substrate intimately related to brain death. Proteomics. 2011 Jan;11(2):239-48. doi: 10.1002/pmic.201000438. Epub 2010 Dec 17. PMID: 21204251.
32: Chang AY, Chan JY, Cheng HL, Tsai CY, Chan SH. Hypoxia-inducible factor 1/heme oxygenase 1 cascade as upstream signals in the prolife role of heat shock protein 70 at rostral ventrolateral medulla during experimental brain stem death. Shock. 2009 Dec;32(6):651-8. doi: 10.1097/SHK.0b013e3181a71027. PMID: 19333137.
33: Chan JY, Wu CH, Tsai CY, Cheng HL, Dai KY, Chan SH, Chang AY. Transcriptional up-regulation of nitric oxide synthase II by nuclear factor-kappaB at rostral ventrolateral medulla in a rat mevinphos intoxication model of brain stem death. J Physiol. 2007 Jun 15;581(Pt 3):1293-307. doi: 10.1113/jphysiol.2007.130872. Epub 2007 Mar 29. PMID: 17395621; PMCID: PMC2170851.
34: Tsai CY, Wu CH, Chan SH, Chang AY. Muscarinic receptor-independent activation of cyclic adenosine monophosphate-dependent protein kinase in rostral ventrolateral medulla underlies the sympathoexcitatory phase of cardiovascular responses during mevinphos intoxication in the rat. Shock. 2007 May;27(5):559-64. doi: 10.1097/01.shk.0000246904.47766.39. PMID: 17438462.
35: Chan JY, Chan SH, Li FC, Tsai CY, Cheng HL, Chang AY. Phasic cardiovascular responses to mevinphos are mediated through differential activation of cGMP/PKG cascade and peroxynitrite via nitric oxide generated in the rat rostral ventrolateral medulla by NOS I and II isoforms. Neuropharmacology. 2005 Jan;48(1):161-72. doi: 10.1016/j.neuropharm.2004.08.012. PMID: 15617736.
研究團隊
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吳嘉琦Wu, Jacqueline C.C.
研究助理
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李真來Lee, Chin-Lai
研究助理
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學術履歷
Education:
2009 Ph.D. Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan
2004 B.S. Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan
Professional Experience:
2019/8 ~ present Associate Professor, Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
2015/9 ~ 2019/7 Assistant Professor, Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
2009/9 ~ 2015/8 Postdoctoral Research Fellow, Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
Awards and Honors:
2019 Editorial Board Fellow, The Journal of Physiology
2018 Awardee, Chang Gung Outstanding Young Medical Researcher Award, Chang Gung Medical
Foundation, Kaohsiung, Taiwan (長庚醫學研究獎-青年獎)
2016 Awardee, Young Investigator Award, Federation of Asian Societies for Molecular Imaging (FASMI) Annual Meeting, Kobe, Japan
2016 Travel Grants and Oral Speaker, the 13th Asia Pacific Federation of Pharmacologists (APFP) Meeting, Bangkok, Thailand
2013 Awardee, Outstanding Young Scientist Oral Presentation Award, the 12th meeting of the Asia Pacific Federation of Pharmacologists (APFP), Shanghai, China
2008 Awardee, Distinguished Postgraduate Student Research Award, the Pharmacological Society in Taiwan, Taiwan
2007 1st prize, SEAWP Poster Prize, the 10th Southeast Asian Western Pacific regional meeting of Pharmacologists (SEAWP), Adelaide, Australia
2006 Participant, the 9th International Brain Research Organization-Asia Pacific Regional Committee (IBRO-APRC) School of Neuroscience, Hong Kong, China
Professional Activities:
2021~ Associate Editor, Natural Sciences
2019 Symposium Organizer and Chair, the 9th Federation of the Asian and Oceanian Physiological Societies Congress (FAOPS2019), Kobe, Japan
2018~ Editorial Board, FASEB BioAdvances
2017 Invited Speaker, Young Investigator Colloquium, the International Society for Neurochemistry (ISN) 2017 Biennial Meeting, Paris, France
2014 Invited Speaker, Young Investigator Colloquium, the 12th meeting of the Asian Pacific Society for Neurochemistry (APSN), Kaohsiung, Taiwan
2012 Invited Speaker, Young Investigator Colloquium, the 11th meeting of the Asian Pacific Society for Neurochemistry (APSN), Kobe, Japan
Professional Societies:
American Physiological Society (APS)
International Society for Neurochemistry (ISN)
The Chinese Physiological Society
The Pharmacological Society in Taiwan
Research Interests:
- Central Cardiovascular Regulation
- Signal Transduction
- Molecular Image
- Pharmacology of pesticides and anesthetics
- Redox signaling and oxidative stress