Xinhai HE, Xintong CHEN, Ziheng YANG, et al. Dexmedetomidine inhibits systemic inflammatory response induced by renal ischemia reperfusion via mediating macrophage polarization[J]. Journal of Third Military Medical University, 2020, 42(6): 611-615.
DOI:
Xinhai HE, Xintong CHEN, Ziheng YANG, et al. Dexmedetomidine inhibits systemic inflammatory response induced by renal ischemia reperfusion via mediating macrophage polarization[J]. Journal of Third Military Medical University, 2020, 42(6): 611-615. DOI: 10.16016/j.1000-5404.201911107.
Dexmedetomidine inhibits systemic inflammatory response induced by renal ischemia reperfusion via mediating macrophage polarization
To explore the effects of dexmedetomidine (Dex) on systemic inflammatory response induced by renal ischemia reperfusion (rIRI) and the possible mechanism.
Methods
2
Fifteen C57BL/6J mice were randomly divided into 3 groups
that is
sham operation group (laparotomy without renal pedicle occlusion)
rIRI group (bilateral renal pedicles was clamped for 60 min with a microvascular clamp)
and rIRI+Dex group (intraperitoneal injection of 25 μg/ml Dex in 15 min prior to bilateral renal ischemia). In 24 h after surgery or reperfusion
the blood samples were harvested and analyzed for counts of neutrophils
monocytes and lymphocytes by blood analyzer and for the serum levels of inflammatory cytokines (TNF-α
IL-1β and IL-10) by ELISA. Western blotting was used to detect iNOS and Arg 1 in the harvested peritoneal macrophages for the polarization.
Results
2
Compared with the mice in the sham group
the counts of neutrophils
monocytes and lymphocytes were significantly elevated (
P
<
0.01)
the serum levels of TNF-α and IL-1β were increased (
P
<
0.01)
and the expression of M1 marker iNOS was enhanced while that of M2 marker Arg 1 was decreased (
P
<
0.01). Dex pretreatment resulted in no significant changes in the counts of neutrophils
monocytes and lymphocytes (
P
>
0.05)
reduced serum levels of TNF-α and IL-1β (
P
<
0.01) and increased level of IL-10 (
P
<
0.01)
and decreased expression of iNOS (
P
<
0.01) as well as increase of Arg 1 (
P
<
0.05) when compared with the indicators in the rIRI group.
Conclusion
2
Dex inhibits the systemic inflammatory response induced by rIRI
which may be associated with modulation of macrophage polarization.
关键词
Keywords
references
YAP S C LEE H T Acute kidney injury and extrarenal organ dysfunction: new concepts and experimental evidence Anesthesiology 2012 116 5 1139 1148 10.1097/ALN.0b013e31824f951b YAP S C, LEE H T. Acute kidney injury and extrarenal organ dysfunction: new concepts and experimental evidence. Anesthesiology, 2012, 116(5): 1139-1148. DOI: 10.1097/ ALN.0b013e31824f951b.
LI B LI Y L TIAN S S Anti-inflammatory effects of perioperative dexmedetomidine administered as an adjunct to general anesthesia: A meta-analysis Sci Rep 2015 5 12342 10.1038/srep12342 LI B, LI Y L, TIAN S S, et al . Anti-inflammatory effects of perioperative dexmedetomidine administered as an adjunct to general anesthesia: A meta-analysis. Sci Rep, 2015, 5: 12342. DOI: 10.1038/srep12342.
JI F H LI Z M YOUNG N Perioperative dexmedetomidine improves mortality in patients undergoing coronary artery bypass surgery J Cardiothorac Vasc Anesth 2014 28 2 267 273 10.1053/j.jvca.2013.06.022 JI F H, LI Z M, YOUNG N, et al . Perioperative dexmedetomidine improves mortality in patients undergoing coronary artery bypass surgery. J Cardiothorac Vasc Anesth, 2014, 28(2): 267-273. DOI: 10.1053/j.jvca.2013. 06.022.
XIA Z Q CHEN S Q YAO X Clinical benefits of dexmedetomidine versus propofol in adult intensive care unit patients: a meta-analysis of randomized clinical trials J Surg Res 2013 185 2 833 843 10.1016/j.jss.2013.06.062 XIA Z Q, CHEN S Q, YAO X, et al . Clinical benefits of dexmedetomidine versus propofol in adult intensive care unit patients: a meta-analysis of randomized clinical trials. J Surg Res, 2013, 185(2): 833-843. DOI: 10.1016/j.jss. 2013.06.062.
GU J T SUN P ZHAO H L Dexmedetomidine provides renoprotection against ischemia-reperfusion injury in mice Crit Care 2011 15 3 R153 10.1186/cc10283 GU J T, SUN P, ZHAO H L, et al . Dexmedetomidine provides renoprotection against ischemia-reperfusion injury in mice. Crit Care, 2011, 15(3): R153. DOI: 10.1186/cc10283.
LI J J CHEN Q HE X H Dexmedetomidine attenuates lung apoptosis induced by renal ischemia-reperfusion injury through α2AR/PI3K/Akt pathway J Transl Med 2018 16 1 78 10.1186/s12967-018-1455-1 LI J J, CHEN Q, HE X H, et al . Dexmedetomidine attenuates lung apoptosis induced by renal ischemia-reperf usion injury through α2AR/PI3K/Akt pathway. J Transl Med, 2018, 16(1): 78. DOI: 10.1186/s12967-018-1455-1.
SHAPOURI-MOGHADDAM A MOHAMMADIAN S VAZINI H Macrophage plasticity, polarization, and function in health and disease J Cell Physiol 2018 233 9 6425 6440 10.1002/jcp.26429 SHAPOURI-MOGHADDAM A, MOHAMMADIAN S, VAZINI H, et al . Macrophage plasticity, polarization, and function in health and disease. J Cell Physiol, 2018, 233(9): 6425-6440. DOI: 10.1002/jcp.26429.
PARK J T Postoperative acute kidney injury Korean J Anesthesiol 2017 70 3 258 10.4097/kjae.2017.70.3.258 PARK J T. Postoperative acute kidney injury. Korean J Anesthesiol, 2017, 70(3): 258. DOI:10.4097/kjae.2017. 70.3.258.
VA/NIH ACUTE RENAL FAILURE TRIAL NETWORK PALEVSKY P M ZHANG J H Intensity of renal support in critically ill patients with acute kidney injury N Engl J Med 2008 359 1 7 20 10.1056/NEJMoa0802639 VA/NIH ACUTE RENAL FAILURE TRIAL NETWORK, PALEVSKY P M, ZHANG J H, et al . Intensity of renal support in critically ill patients with acute kidney injury. N Engl J Med, 2008, 359(1): 7-20. DOI: 10.1056/ NEJMoa0802639.
JOHNSTON L K RIMS C R GILL S E Pulmonary macrophage subpopulations in the induction and resolution of acute lung injury Am J Respir Cell Mol Biol 2012 47 4 417 426 10.1165/rcmb.2012-0090OC JOHNSTON L K, RIMS C R, GILL S E, et al . Pulmonary macrophage subpopulations in the induction and resolution of acute lung injury. Am J Respir Cell Mol Biol, 2012, 47(4): 417-426. DOI: 10.1165/rcmb.2012-0090OC.
KRENKEL O TACKE F Liver macrophages in tissue homeostasis and disease Nat Rev Immunol 2017 17 5 306 321 10.1038/nri.2017.11 KRENKEL O, TACKE F. Liver macrophages in tissue homeostasis and disease. Nat Rev Immunol, 2017, 17(5): 306-321. DOI: 10.1038/nri.2017.11.
YIN J VALIN K L DIXON M L The role of microglia and macrophages in CNS homeostasis, autoimmunity, and cancer J Immunol Res 2017 2017 5150678 10.1155/2017/5150678 YIN J, VALIN K L, DIXON M L, et al . The role of microglia and macrophages in CNS homeostasis, autoimmunity, and cancer. J Immunol Res, 2017, 2017: 5150678. DOI: 10.1155/2017/5150678.
MA J B CHEN Q LI J J Dexmedetomidine-mediated prevention of renal ischemia-reperfusion injury depends in part on cholinergic anti-inflammatory mechanisms Anesth Analg 2018 10.1213/ANE.0000000000003820 MA J B, CHEN Q, LI J J, et al . Dexmedetomidine-mediated prevention of renal ischemia-reperfusion injury depends in part on cholinergic anti-inflammatory mechanisms. Anesth Analg, 2018. DOI: 10.1213/ANE.00000000000 03820.
INOUE T ABE C KOHRO T Non-canonical cholinergic anti-inflammatory pathway-mediated activation of peritoneal macrophages induces Hes1 and blocks ischemia/reperfusion injury in the kidney Kidney Int 2019 95 3 563 576 10.1016/j.kint.2018.09.020 INOUE T, ABE C, KOHRO T, et al . Non-canonical cholinergic anti-inflammatory pathway-mediated activation of peritoneal macrophages induces Hes1 and blocks ischemia/reperfusion injury in the kidney. Kidney Int, 2019, 95(3): 563-576. DOI: 10.1016/j.kint.2018.09.020.
QIAO H SANDERS R D MA D Q Sedation improves early outcome in severely septic Sprague Dawley rats Crit Care 2009 13 4 R136 10.1186/cc8012 QIAO H, SANDERS R D, MA D Q, et al . Se dation improves early outcome in severely septic Sprague Dawley rats. Crit Care, 2009, 13(4): R136. DOI: 10.1186/cc8012.
PANDHARIPANDE P P SANDERS R D GIRARD T D Effect of dexmedetomidine versus lorazepam on outcome in patients with sepsis: an a priori-designed analysis of the MENDS randomized controlled trial Crit Care 2010 14 2 R38 10.1186/cc8916 PANDHARIPANDE P P, SANDERS R D, GIRARD T D, et al . Effect of dexmedetomidine versus lorazepam on outcome in patients with sepsis: an a priori-designed analysis of the MENDS randomized controlled trial. Crit Care, 2010, 14(2): R38. DOI: 10.1186/cc8916.
MALYSHEV I MALYSHEV Y Current concept and update of the macrophage plasticity concept: intracellular mechanisms of reprogramming and M3 macrophage "Switch" phenotype Biomed Res Int 2015 2015 341308 10.1155/2015/341308 MALYSHEV I, MALYSHEV Y. Current concept and update of the macrophage plasticity concept: intracellular mechanisms of reprogramming and M3 macrophage "Switch" phenotype. Biomed Res Int, 2015, 2015: 341308. DOI: 10.1155/2015/341308.
MURRAY P J Macrophage polarization Annu Rev Physiol 2017 79 541 566 10.1146/annurev-physiol-022516-034339 MURRAY P J. Macrophage polarization. Annu Rev Physiol, 2017, 79: 541-566. DOI: 10.1146/annurev-physiol- 022516-034339.
GRIMALDI A D'ALESSANDRO G GOLIA M T KCa3.1 inhibition switches the phenotype of glioma-infiltrating microglia/macrophages Cell Death Dis 2016 7 e2174 10.1038/cddis.2016.73 GRIMALDI A, D'ALESSANDRO G, GOLIA M T, et al . KCa3.1 inhibition switches the phenotype of glioma-infiltrating microglia/macrophages. Cell Death Dis, 2016, 7: e2174. DOI: 10.1038/cddis.2016.73.
CHEN Q YI B MA J B A2-adrenoreceptor modulated FAK pathway induced by dexmedetomidine attenuates pulmonary microvascular hyper-permeability following kidney injury Oncotarget 2016 7 35 55990 56001 10.18632/oncotarget.10809 CHEN Q, YI B, MA J B, et al . A2-adrenoreceptor modulated FAK pathway induced by dexmedetomidine attenuates pulmonary microvascular hyper-permeability following kidney injury. Oncotarget, 2016, 7(35): 55990-56001. DOI: 10.18632/oncotarget.10809.
FU Q F LIU Y FAN Y Alpha-enolase promotes cell glycolysis, growth, migration, and invasion in non-small cell lung cancer through FAK-mediated PI3K/AKT pathway J Hematol Oncol 2015 8 22 10.1186/s13045-015-0117-5 FU Q F, LIU Y, FAN Y, et al . Alpha-enolase promotes cell glycolysis, growth, migration, and invasion in non-small cell lung cancer through FAK-mediated PI3K/AKT pathway. J Hematol Oncol, 2015, 8: 22. DOI: 10.1186/s13045-015- 0117-5.
Protective effect of dexmedetomidine on intestinal barrier function in septic rats
Low-intensity pulsed ultrasound suppresses synovitis by modulating polarization of synovial macrophages in mice with osteoarthritis
Reparative role of dexmedetomidine in lung injury secondary to acute kidney injury
Dexmedetomidine alleviates sevoflurane-induced cognitive dysfunction in neonatal rats by inhibiting the mTOR/NF-κB signaling pathway
Hypoxia drives spermatogenic impairment by triggering lysosome-dependent death of Leydig cells via M1 macrophage polarization
Related Author
Shijie ZHOU
Li WANG
Liangming LIU
Tao LI
Hong YAN
Bin ZHANG
Zhenhong NI
Peng YANG
Related Institution
State Key Laboratory of Trauma, Burns and Combined Injuries, Department of War Wound Shock and Transfusion, Institute of Surgery Research, Army Medical Center of PLA
Department of Anesthesiology, Army Medical Center of PLA
Department of Anesthesiology, the First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine
Reproductive Medical Center, First Affiliated Hospital, College of Basic Medical Science,Army Medical University (Third Military Medical University)
Institute of Immunology, College of Basic Medical Science,Army Medical University (Third Military Medical University)