右美托咪定对磷脂酰肌醇-3-激酶/蛋白激酶B信号通路的影响研究进展
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摘要
磷脂酰肌醇-3-激酶/蛋白激酶B (PI3K/Akt)信号通路是典型的抗凋亡通路。右美托咪定是新型的高选择性α2-肾上腺素受体激动剂,因其副作用少,具有多器官保护作用而被广泛应用于临床。右美托咪定通过激活PI3K/Akt信号通路,可以抑制或增强下游相关靶蛋白的表达进而发挥其特定的保护作用。本文对右美托咪定对PI3K/Akt信号通路的影响研究进展进行了综述。
Phosphatidylmyosidyl 3-kinase/protein kinase B( PI3 K/Akt) is a typical anti-apoptosis signaling pathway. Dexmedetomidine is a novel high selectivity α2-adrenergic receptor agonist which is widely used in clinical practice because of its multi-organ protective effect and low side effects. Dexmedetomidine can up or down regulate downstream target proteins and then plays specific protective roles through activating PI3 K/Akt signaling pathway. This paper reviewed advanced researches on the effect of dexmedetomidine on PI3 K/Akt signaling pathway.
Phosphatidylmyosidyl 3-kinase/protein kinase B( PI3 K/Akt) is a typical anti-apoptosis signaling pathway. Dexmedetomidine is a novel high selectivity α2-adrenergic receptor agonist which is widely used in clinical practice because of its multi-organ protective effect and low side effects. Dexmedetomidine can up or down regulate downstream target proteins and then plays specific protective roles through activating PI3 K/Akt signaling pathway. This paper reviewed advanced researches on the effect of dexmedetomidine on PI3 K/Akt signaling pathway.
引文
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[8] Wan Q,Xu L,Bo Y. Effects of Dexmedetomidine combined with Dezocine on cognition function and hippocampalmicroglia activation of rats[J]. Int J Clin Exp Med,2014,7(9):2787-2792.
[9]华敬,陶爱玲.右美托咪定在冠脉搭桥围术期血流动力学的观察[J].中国临床医生杂志,2017,45(7):87-88. DOI:10.3969/j. issn. 2095-8552. 2017. 07. 033.Hua J,Tao AL. Observation of hemodynamics of dexmedetomidine during perioperative period of coronary artery bypass grafting[J].Chinese Journal for Clinicians,2017,45(7):87-88. DOI:10.3969/j. issn. 2095-8552. 2017. 07. 033.
[10]崔艳,李伟敬,杜文敏,等.右美托咪定对大鼠肾缺血再灌注诱发肺损伤的影响[J].中国医药,2015,10(9):1297-1299. DOI:10. 3760/cma. j. issn. 1673-4777. 2015. 09. 014.Cui Y,Li WJ,Du WM,et al. Effect of dexmedetomidine on lung injury induced by renal ischemia reperfusion in rats[J]. China Medicine,2015,10(9):1297-1299. DOI:10. 3760/cma. j. issn.1673-4777. 2015. 09. 014.
[11]吴文峰,宁雪,尧永华.右美托咪定预处理对大鼠肝脏缺血再灌注后急性肾损伤的影响[J].中国医药导报,2014,11(3):17-19.Wu WF,Ning X,Yao YH. Effects of dexmedetomidine preconditioning on acute kidney injury induced by hepatic ischemic-reperfusion[J]. China Medical Herald,2014,11(3):17-19.
[12] Wu GJ,Chen JT,Tsai HC,et al. Protection of dexmedetomidine against ischemia/reperfusion-induced apoptotic insults to neuronal cells occurs via an intrinsic mitochondria-dependent pathway[J]. J Cell Biochem,2017,118(9):2635-2644. DOI:10. 1002/jcb.25847.
[13] Badger SA,Jones C,Mc Caigue M,et al. Cytokine response to portal endotoxaemia and neutrophil stimulation in obstructive jaundice[J]. Eur J Gastroenterol Hepatol,2012,24(1):25-32.DOI:10. 1097/MEG. 0b013e32834b0dd3.
[14] Si YN,Bao HG,Xu L,et al. Dexmedetomidine protects against ischemia/reperfusion injury in rat kidney[J]. Eur Rev Med Pharmacol Sci,2014,18(13):1843-1851.
[15]张伟.右美托咪定通过PI3K/Akt/HIF-1α信号通路减轻肺缺血再灌注损伤[D].郑州:郑州大学,2016.Zhang W. Dexmedetomidine attenuates lung ischemia-reperfusion injury through PI3K/Akt/HIF-1alpha signaling pathway[D].Zhengzhou:Zhengzhou University,2016.
[16] Li J,Chen Q,He X,et al. Dexmedetomidine attenuates lung apoptosis induced by renal ischemia-reperfusion injurythroughα2AR/PI3K/Akt pathway[J]. J Transl Med,2018,16(1):78.DOI:10. 1186/s12967-018-1455-1.
[17] Wang H,Zhang S,Xu S,et al. The efficacy and mechanism of dexmedetomidine in myocardial apoptosis via the renin-angiotensinaldosterone system[J]. J Renin Angiotensin Aldosterone Syst,2015,16(4):1274-1280. DOI:10. 1177/1470320314546941.
[18]肖如红,张忠,米志华,等. PI3K/Akt信号传导通路在右美托咪定抗大鼠肢端缺血/再灌注致急性肺损伤中的作用[J].北方药学,2017,14(1):140-141,137. DOI:10. 3969/j. issn. 1672-8351. 2017. 01. 120.Xiao RH,Zhang Z,Mi ZH,et al. The role of PI3K/A kt signaling pathway in the protection of dexmedetomidine against limb ischemia/reperfusion(I/R)-induced acute lung injury in rats[J]. Journal of North Pharmacy,2017,14(1):140-141,137. DOI:10. 3969/j.issn. 1672-8351. 2017. 01. 120.
[19]汤旭,陆克银. PI3K-Akt-HIF-α信号通路在右美托咪定减轻大鼠肝缺血/再灌注致肺损伤中的作用[J].北方药学,2017,14(7):123-124. DOI:10. 3969/j. issn. 1672-8351. 2017. 07. 104.Tang X,Lu KY. The role of PI3K-Akt-HIF-αsignaling pathway in the protection of dexmedetomidine against limb liver ischemia/reperfusion(I/R)-induced acute lung injury in rats[J]. Journal of North Pharmacy,2017,14(7):123-124. DOI:10. 3969/j. issn.1672-8351. 2017. 07. 104.
[20] Meng L,Li L,Lu S,et al. The protective effect of dexmedetomidine on LPS-induced acute lung injury through the HMGB1-mediated TLR4/NF-κB and PI3K/Akt/m TOR pathways[J]. Mol Immunol,2018,94:7-17. DOI:10. 1016/j. molimm. 2017. 12. 008.
[21]姜远旭,张雪萍,陶明哲,等.右美托咪定器官保护作用的研究进展[J].国际麻醉学与复苏杂志,2013,34(11):1024-1027.DOI:10. 3760/cma. j. issn. 1673-4378. 2013. 11. 016.Jiang YX,Zhang XP,Tao MZ,et al. The role of PI3K-Akt-HIF-αsignaling pathway in the protection of dexmedetomidine against limb liver ischemia/reperfusion(I/R)-induced acute lung injury in rats[J].Journal of North Pharmacy,2013,34(11):1024-1027. DOI:10.3760/cma. j. issn. 1673-4378. 2013. 11. 016.
[22] Sahin T,BegeZ,Toprak H,et al. The effects of dexmedetomidine on liver ischemia-reperfusion injury in rats[J]. J Surg Res,2013,183(1):385-390. DOI:10. 1016/j. jss. 2012. 11. 034.
[23]解春艳,李云峰,梁江水,等.右美托咪定对肠缺血再灌注肺损伤中自噬与凋亡的影响[J].中华结核和呼吸杂志,2015,38(10):761-764. DOI:10. 3760/cma. j. issn. 1001-0939. 2015. 10. 010.Xie CY,Li YF,Liang JS,et al. The effect of dexmedetomidine on autophagy and apoptosis in intestinal ischemia reperfusion-induced lung injury[J]. Chinese Journal of Tuberculosis and Respiratory Diseases,2015,38(10):761-764. DOI:10. 3760/cma. j. issn.1001-0939. 2015. 10. 010.
[24]周丽芳,韦祎,吕靖,等.右美托咪定对丙泊酚麻醉新生大鼠海马PI3K/Akt信号通路的影响[J].临床麻醉学杂志,2017,33(1):59-62. DOI:10. 3969/j. issn. 1004-5805. 2017. 01. 015.Zhou LF,Wei Y,Lyu J,et al. Effects of dexmedetomidine on PI3K/Akt pathway in hippocampus of propofol anesthetized neonatal rats[J]. Journal of Clinical Anesthesiology,2017,33(1):59-62. DOI:10. 3969/j. issn. 1004-5805. 2017. 01. 015.
[25] Lv J,Wei Y,Chen Y,et al. Dexmedetomidine attenuates propofolinduce neuroapoptosis partly via the activation of the PI3k/Akt/GSK3βpathway in the hippocampus of neonatal rats[J]. Environ Toxicol Pharmacol,2017,52:121-128. DOI:10. 1016/j. etap.2017. 03. 017.
[2] Wu QL,Shen T,Shao LL,et al. Ischemic postconditioning mediates cardioprotection via PI3K/GSK-3β/β-catenin signaling pathway in ischemic rat myocardium[J]. Shock,2012,38(2):165-169. DOI:10. 1097/SHK. 0b013e31825b5633.
[3]陈勇,付贞,范林,等. PI3K/Akt信号通路在肝脏缺血再灌注损伤中的研究进展[J].中国临床医学,2018,25(1):103-107.DOI:10. 12025/j. issn. 1008-6358. 2018. 20170926.Chen Y,Fu Z,Fan L,et al. Research progresses of PI3K/Akt signaling pathway in hepatic ischemia-reperfusion injury[J].Chinese Journal of Clinical Medicine,2018,25(1):103-107.DOI:10. 12025/j. issn. 1008-6358. 2018. 20170926.
[4]董超,罗春香,杨润祥. PI3K/AKT通路及其抑制剂在肺癌治疗中的研究进展[J].中国临床医生杂志,2017,45(10):13-16.DOI:10. 3969/j. issn. 2095-8552. 2017. 10. 006.Dong C,Luo CX,Yang RX. Research progress of PI3K/AKT pathway and its inhibitors in the treatment of lung cancer[J].Chinese Journal for Clinicians,2017,45(10):13-16. DOI:10.3969/j. issn. 2095-8552. 2017. 10. 006.
[5]李锐锐,苗劲蔚. PI3K/Akt/m TOR信号转导通路与宫颈癌关系研究进展[J].中国医刊,2013,48(6):18-20. DOI:10. 3969/j.issn. 1008-1070. 2013. 06. 008.Li RR,Miao JW. Progress in the relationship between PI3K/Akt/m TOR signal transduction pathway and cervical cancer[J].Chinese Journal of Medicine,2013,48(6):18-20. DOI:10.3969/j. issn. 1008-1070. 2013. 06. 008.
[6]吴松,虞桂平,薛涛. PI3K-mTOR信号通路抑制剂抗肿瘤研究新进展[J].中国医药导报,2015,12(1):161-164,168.Wu S,Yu GP,Xue T. Research new progress on inhibitors antitumor of PI3K-mTOR signaling pathway[J]. China Medical Herald,2015,12(1):161-164,168.
[7]李冬冬,张红.磷脂酰肌醇3激酶/蛋白质丝氨酸苏氨酸激酶/核转录因子κB信号通路对细胞凋亡影响的研究进展[J].中国医药导报,2014,11(33):166-168.Li DD,Zhang H. Research progress of correlation between phosphatidylinositol 3-kinase/protein kinase B/nuclear factor-kappa B signal pathway and cell apoposiss[J]. China Medical Herald,2014,11(33):166-168.
[8] Wan Q,Xu L,Bo Y. Effects of Dexmedetomidine combined with Dezocine on cognition function and hippocampalmicroglia activation of rats[J]. Int J Clin Exp Med,2014,7(9):2787-2792.
[9]华敬,陶爱玲.右美托咪定在冠脉搭桥围术期血流动力学的观察[J].中国临床医生杂志,2017,45(7):87-88. DOI:10.3969/j. issn. 2095-8552. 2017. 07. 033.Hua J,Tao AL. Observation of hemodynamics of dexmedetomidine during perioperative period of coronary artery bypass grafting[J].Chinese Journal for Clinicians,2017,45(7):87-88. DOI:10.3969/j. issn. 2095-8552. 2017. 07. 033.
[10]崔艳,李伟敬,杜文敏,等.右美托咪定对大鼠肾缺血再灌注诱发肺损伤的影响[J].中国医药,2015,10(9):1297-1299. DOI:10. 3760/cma. j. issn. 1673-4777. 2015. 09. 014.Cui Y,Li WJ,Du WM,et al. Effect of dexmedetomidine on lung injury induced by renal ischemia reperfusion in rats[J]. China Medicine,2015,10(9):1297-1299. DOI:10. 3760/cma. j. issn.1673-4777. 2015. 09. 014.
[11]吴文峰,宁雪,尧永华.右美托咪定预处理对大鼠肝脏缺血再灌注后急性肾损伤的影响[J].中国医药导报,2014,11(3):17-19.Wu WF,Ning X,Yao YH. Effects of dexmedetomidine preconditioning on acute kidney injury induced by hepatic ischemic-reperfusion[J]. China Medical Herald,2014,11(3):17-19.
[12] Wu GJ,Chen JT,Tsai HC,et al. Protection of dexmedetomidine against ischemia/reperfusion-induced apoptotic insults to neuronal cells occurs via an intrinsic mitochondria-dependent pathway[J]. J Cell Biochem,2017,118(9):2635-2644. DOI:10. 1002/jcb.25847.
[13] Badger SA,Jones C,Mc Caigue M,et al. Cytokine response to portal endotoxaemia and neutrophil stimulation in obstructive jaundice[J]. Eur J Gastroenterol Hepatol,2012,24(1):25-32.DOI:10. 1097/MEG. 0b013e32834b0dd3.
[14] Si YN,Bao HG,Xu L,et al. Dexmedetomidine protects against ischemia/reperfusion injury in rat kidney[J]. Eur Rev Med Pharmacol Sci,2014,18(13):1843-1851.
[15]张伟.右美托咪定通过PI3K/Akt/HIF-1α信号通路减轻肺缺血再灌注损伤[D].郑州:郑州大学,2016.Zhang W. Dexmedetomidine attenuates lung ischemia-reperfusion injury through PI3K/Akt/HIF-1alpha signaling pathway[D].Zhengzhou:Zhengzhou University,2016.
[16] Li J,Chen Q,He X,et al. Dexmedetomidine attenuates lung apoptosis induced by renal ischemia-reperfusion injurythroughα2AR/PI3K/Akt pathway[J]. J Transl Med,2018,16(1):78.DOI:10. 1186/s12967-018-1455-1.
[17] Wang H,Zhang S,Xu S,et al. The efficacy and mechanism of dexmedetomidine in myocardial apoptosis via the renin-angiotensinaldosterone system[J]. J Renin Angiotensin Aldosterone Syst,2015,16(4):1274-1280. DOI:10. 1177/1470320314546941.
[18]肖如红,张忠,米志华,等. PI3K/Akt信号传导通路在右美托咪定抗大鼠肢端缺血/再灌注致急性肺损伤中的作用[J].北方药学,2017,14(1):140-141,137. DOI:10. 3969/j. issn. 1672-8351. 2017. 01. 120.Xiao RH,Zhang Z,Mi ZH,et al. The role of PI3K/A kt signaling pathway in the protection of dexmedetomidine against limb ischemia/reperfusion(I/R)-induced acute lung injury in rats[J]. Journal of North Pharmacy,2017,14(1):140-141,137. DOI:10. 3969/j.issn. 1672-8351. 2017. 01. 120.
[19]汤旭,陆克银. PI3K-Akt-HIF-α信号通路在右美托咪定减轻大鼠肝缺血/再灌注致肺损伤中的作用[J].北方药学,2017,14(7):123-124. DOI:10. 3969/j. issn. 1672-8351. 2017. 07. 104.Tang X,Lu KY. The role of PI3K-Akt-HIF-αsignaling pathway in the protection of dexmedetomidine against limb liver ischemia/reperfusion(I/R)-induced acute lung injury in rats[J]. Journal of North Pharmacy,2017,14(7):123-124. DOI:10. 3969/j. issn.1672-8351. 2017. 07. 104.
[20] Meng L,Li L,Lu S,et al. The protective effect of dexmedetomidine on LPS-induced acute lung injury through the HMGB1-mediated TLR4/NF-κB and PI3K/Akt/m TOR pathways[J]. Mol Immunol,2018,94:7-17. DOI:10. 1016/j. molimm. 2017. 12. 008.
[21]姜远旭,张雪萍,陶明哲,等.右美托咪定器官保护作用的研究进展[J].国际麻醉学与复苏杂志,2013,34(11):1024-1027.DOI:10. 3760/cma. j. issn. 1673-4378. 2013. 11. 016.Jiang YX,Zhang XP,Tao MZ,et al. The role of PI3K-Akt-HIF-αsignaling pathway in the protection of dexmedetomidine against limb liver ischemia/reperfusion(I/R)-induced acute lung injury in rats[J].Journal of North Pharmacy,2013,34(11):1024-1027. DOI:10.3760/cma. j. issn. 1673-4378. 2013. 11. 016.
[22] Sahin T,BegeZ,Toprak H,et al. The effects of dexmedetomidine on liver ischemia-reperfusion injury in rats[J]. J Surg Res,2013,183(1):385-390. DOI:10. 1016/j. jss. 2012. 11. 034.
[23]解春艳,李云峰,梁江水,等.右美托咪定对肠缺血再灌注肺损伤中自噬与凋亡的影响[J].中华结核和呼吸杂志,2015,38(10):761-764. DOI:10. 3760/cma. j. issn. 1001-0939. 2015. 10. 010.Xie CY,Li YF,Liang JS,et al. The effect of dexmedetomidine on autophagy and apoptosis in intestinal ischemia reperfusion-induced lung injury[J]. Chinese Journal of Tuberculosis and Respiratory Diseases,2015,38(10):761-764. DOI:10. 3760/cma. j. issn.1001-0939. 2015. 10. 010.
[24]周丽芳,韦祎,吕靖,等.右美托咪定对丙泊酚麻醉新生大鼠海马PI3K/Akt信号通路的影响[J].临床麻醉学杂志,2017,33(1):59-62. DOI:10. 3969/j. issn. 1004-5805. 2017. 01. 015.Zhou LF,Wei Y,Lyu J,et al. Effects of dexmedetomidine on PI3K/Akt pathway in hippocampus of propofol anesthetized neonatal rats[J]. Journal of Clinical Anesthesiology,2017,33(1):59-62. DOI:10. 3969/j. issn. 1004-5805. 2017. 01. 015.
[25] Lv J,Wei Y,Chen Y,et al. Dexmedetomidine attenuates propofolinduce neuroapoptosis partly via the activation of the PI3k/Akt/GSK3βpathway in the hippocampus of neonatal rats[J]. Environ Toxicol Pharmacol,2017,52:121-128. DOI:10. 1016/j. etap.2017. 03. 017.