右美托咪定对脓毒症小鼠的脑保护作用

doi:10.3969/j.issn.1002-1949.2018.12.016

Chinese Journal of Critical Care Medicine

2018, Vol. 38

Issue (12): 1090-1094 DOI: 10.3969/j.issn.1002-1949.2018.12.016

The protective effects of dexmedetomidine on sepsis-associated encephalopathy in mice

Wang Zhi-yong, Yang Yong-yan, Yu Yong-hao

Department of Anesthesiology, General Hospital of Tianjin Medical University, Anesthesiology Research Institute of Tianjin Medical University, Tianjin 300052, China

Abstract
Figure/Table
References (24)
Related Citation (15)

Download: PDF (585 KB) HTML (1 KB)
Export: BibTeX | EndNote (RIS)

Abstract Objective This study aims to investigate the effects of dexmedetomidine (DEX) on the survival rate and brain injury using a mice model of sepsis-associated encephalopathy (SAE). Methods Male ICR mice weighing 20-25 g were randomly divided into 4 groups: Sham, CLP, CLP+DEX and CLP+DEX+Y groups. Mice underwent cecal ligation and puncture (CLP) or sham operation. DEX (10 μg/kg) was injected 4 times (0, 2, 4, 6 h) after CLP operation in group CLP+DEX and group CLP+DEX+Y. Yohimbine (3 mg/kg) was given to group CLP+DEX+Y 30 min before operation. Brain water content, activities of SOD and levels of MDA in hippocampus were detected. HE staining, Nissl staining and TUNEL assay were used to observe the histopathologic changes and neuronal apoptosis. Results DEX treatment markedly alleviated pathological damage and brain edema caused by CLP operation. Levels of oxidative products decreased and the activities of antioxidant enzymes increased in brain. Yohimbine can counteract the effect of DEX. Conclusion DEX targets on adrenergic α2 receptors to show the brain protective effect, which is linked to the decreased levels of oxidative products and the increased activities of antioxidant enzymes in brain. DEX may be a promising therapeutic strategy to relieve SAE.

Key words： Dexmedetomidine (DEX) Sepsis Sepsis-associated encephalopathy (SAE) Adrenergic α2 receptors

Corresponding Authors: Yu Yong-hao, E-mail: yuyonghao@126.com

	Service

	E-mail this article
	Add to my bookshelf
	Add to citation manager
	E-mail Alert
	RSS
	Articles by authors
	Wang Zhi-yong
	Yang Yong-yan
	Yu Yong-hao

Cite this article:

Wang Zhi-yong,Yang Yong-yan,Yu Yong-hao. The protective effects of dexmedetomidine on sepsis-associated encephalopathy in mice[J]. Chinese Journal of Critical Care Medicine, 2018, 38(12): 1090-1094.

URL:

http://www.cnemergency.org.cn/EN/10.3969/j.issn.1002-1949.2018.12.016 OR http://www.cnemergency.org.cn/EN/Y2018/V38/I12/1090

［1］Hotchkiss RS, Moldawer LL, Opal SM, et al. Sepsis and septic shock ［J］. Nat Rev Dis Primers, 2016, 2（6）: 16045. ［2］Jacob A, Brorson JR, Alexander JJ. Septic encephalopathy: inflammation in man and mouse［J］. Neurochem Int, 2011, 58(4):472-476. ［3］Iwashyna TJ, Ely EW, Smith DM, et al. Long-term cognitive impairment and functional disability among survivors of severe sepsis ［J］. JAMA, 2010, 304(16):1787-1794. ［4］Naaz S, Ozair E. Dexmedetomidine in current anaesthesia practice-a review ［J］. J Clin Diagn Res, 2014, 8(10):GE01-4. ［5］Erbatur ME, Sezen SC, Bayraktar AC, et al. Effects of dexmedetomidine on renal tissue after lower limb ischemia reperfusion injury in streptozotocin induced diabetic rats ［J］. Libyan J Med, 2017, 12(1):127. ［6］Riveros R, Makarova N, Riveros-Perez E, et al. Utility and clinical profile of dexmedetomidine in pediatric cardiac catheterization procedures: amatched controlled analysis［J］. Semin Cardiothorac Vasc Anesth, 2017, 21(4): 330-340. ［7］Luo C, Ouyang MW, Fang YY, et al. Dexmedetomidine Protects Mouse Brain from Ischemia-Reperfusion Injury via Inhibiting Neuronal Autophagy through Up-Regulating HIF-1α［J］. Front Cell Neurosci, 2017, 11: 197. ［8］Koca U, Olguner CG, Ergur BU, et al. The effects of dexmedetomidine on secondary acute lung and kidney injuries in the rat model of intra-abdominal sepsis［J］. ScientificWorldJournal, 2013, 2013:292. ［9］Xie K, Yu Y, Huang Y, et al. Molecular hydrogen ameliorates lipopolysaccharide-induced acute lung injury in mice through reducing inflammation and apoptosis ［J］. Shock, 2012, 37(5):548-555. ［10］Liu Z, Wang Y, Wang Y, et al. Dexmedetomidine attenuates inflammatory reaction in the lung tissues of septic mice by activating cholinergic anti-inflammatory pathway［J］. Int Immunopharmacol, 2016, 35（7）:210-216.  ［11］Liu Z, Wang Y, Ning Q, et al. The role of spleen in the treatment of experimental lipopolysaccharide-induced sepsis with dexmedetomidine［J］. Springerplus, 2015, 4（12）:800. ［12］Dejager L, Pinheiro I, Dejonckheere E, et al. Cecal ligation and puncture: the gold standard model for polymicrobial sepsis［J］. Trends Microbiol, 2011, 19(4):198-208. ［13］Vaughns JD, Martin C, Nelson J, et al. Dexmedetomidine as an adjuvant for perioperative pain management in adolescents undergoing bariatric surgery: an observational cohort study［J］. J Pediatr Surg, 2017, 52(11):1787-1790. ［14］Zhang Y, Jia S, Gao T, et al. Dexmedetomidine mitigate acute lung injury by inhibiting IL-17-induced inflammatory reaction［J］. Immunobiology, 2018, 223(1): 32-37. ［15］Chen Z, Ding T, Ma CG. Dexmedetomidine (DEX) protects against hepatic ischemia/reperfusion (I/R) injury by suppressing inflammation and oxidative stress in NLRC5 deficient mice［J］. Biochem Biophys Res Commun, 2017, 493(2): 1143-1150. ［16］Shen M, Wang S, Wen X, et al. Dexmedetomidine exerts neuroprotective effect via the activation of the PI3K/Akt/mTOR signaling pathway in rats with traumatic brain injury［J］. Biomed Pharmacother, 2017, 95（11）:885-893. ［17］Hoffman WE, Kochs E, Werner C, et al. Dexmedetomidine improves neurologic outcome from incomplete ischemia in the rat reversal by the alpha 2-adrenergic antagonist atipamezole ［J］. Anesthesiology, 1991, 75(2):328-332. ［18］Eser O, Fidan H, SahinO, et al. The influence of dexmedetomidine on ischemic rat hippocampus［J］. Brain Res, 2008, 1218:250-256.  ［19］Pandharipande PP, Sanders RD, Girard TD, et al. Effect of dexmedetomidine versus lorazepam on outcome in patients with sepsis: an a priori-designed analysis of the MENDS randomized controlled trial［J］. Crit Care, 2010， 14(2):R38.  ［20］Guo F, Wang Q, Yan CY, et al. Clinical application of different sedation regimen in patients with septic shock［J］. Zhonghua Yi Xue Za Zhi, 2016, 96(22):1758-1761. ［21］Matsuda A, Jacob A, Wu R, et al. Novel therapeutic targets for sepsis: regulation of exaggerated inflammatory responses［J］. J Nippon Med Sch, 2012, 79(1): 4-18. ［22］Rodríguez-Rodríguez A, Egea-Guerrero JJ, Murillo-Cabezas F, et al. Oxidative stress in traumatic brain injury［J］. Curr Med Chem, 2014, 21(10):1201-1211. ［23］Bahar I, Elay G, Baskol G, et al. Increased DNA damage and increased apoptosis and necrosis in patients with severe sepsis and septic shock［J］. J Crit Care, 2017, 43:271-275. ［24］Oami T, Watanabe E, Hatano M, et al. Blocking liver autophagy accelerates apoptosis and mitochondrial injury in hepatocytes and reduces time to mortality in a murine sepsis model［J］. Shock, 2017, 10：1097.