PMID- 32670056
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220415
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 11
DP  - 2020
TI  - Dexmedetomidine Enhances Autophagy via alpha2-AR/AMPK/mTOR Pathway to Inhibit the 
      Activation of NLRP3 Inflammasome and Subsequently Alleviates 
      Lipopolysaccharide-Induced Acute Kidney Injury.
PG  - 790
LID - 10.3389/fphar.2020.00790 [doi]
LID - 790
AB  - BACKGROUND: Acute kidney injury (AKI) is a severe complication of sepsis; 
      however, no effective drugs have been found. Activation of the nucleotide-binding 
      domain-like receptor protein 3 (NLRP3) inflammasome is a major pathogenic 
      mechanism of AKI induced by lipopolysaccharide (LPS). Autophagy, a process of 
      intracellular degradation related to renal homeostasis, effectively restricts 
      inflammatory responses. Herein, we explored the potential protective mechanisms 
      of dexmedetomidine (DEX), which has confirmed anti-inflammatory effects, on 
      LPS-induced AKI. METHODS: AKI was induced in rats by injecting 10 mg/kg of LPS 
      intraperitoneally (i.p.). Wistar rats received intraperitoneal injections of DEX 
      (30 microg/kg) 30 min before an intraperitoneal injection of LPS. Atipamezole (ATI) 
      (250 microg/kg) and 3-methyladenine (3-MA) (15 mg/kg) were intraperitoneally injected 
      30 min before the DEX injection. RESULTS: DEX significantly attenuated renal 
      injury. Furthermore, DEX decreased activation of the NLRP3 inflammasome and 
      expression of interleukins 1beta and 18. In addition, autophagy-related protein and 
      gene analysis indicated that DEX could significantly enhance autophagy. Finally, 
      we verified the pharmacological effects of DEX on the 5'-adenosine 
      monophosphate-activated protein kinase (AMPK)/mechanistic target of rapamycin 
      (mTOR) pathway. Atip and 3-MA significantly reversed the protective effects of 
      DEX. CONCLUSIONS: Our results suggest that the protective effects of DEX were 
      mediated by enhanced autophagy via the alpha(2)-adrenoreceptor/AMPK/mTOR pathway, 
      which decreased activation of the NLRP3 inflammasome. Above all, we verified the 
      renal protective effects of DEX and offer a new treatment strategy for AKI.
CI  - Copyright (c) 2020 Yang, Feng, Zhao, Zhang, Cui, Wei, Yang and Fan.
FAU - Yang, Tianyuan
AU  - Yang T
AD  - Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, 
      College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
FAU - Feng, Xiujing
AU  - Feng X
AD  - Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, 
      College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
FAU - Zhao, Yuan
AU  - Zhao Y
AD  - Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, 
      College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
FAU - Zhang, Haiyang
AU  - Zhang H
AD  - Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, 
      College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
FAU - Cui, Hailin
AU  - Cui H
AD  - Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, 
      College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
FAU - Wei, Mian
AU  - Wei M
AD  - Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, 
      College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
FAU - Yang, Haotian
AU  - Yang H
AD  - Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, 
      College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
FAU - Fan, Honggang
AU  - Fan H
AD  - Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, 
      College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
LA  - eng
PT  - Journal Article
DEP - 20200624
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC7326938
OTO - NOTNLM
OT  - NLRP3 inflammasome
OT  - acute kidney injury
OT  - autophagy
OT  - dexmedetomidine
OT  - alpha2-AR/AMPK/mTOR pathway
EDAT- 2020/07/17 06:00
MHDA- 2020/07/17 06:01
PMCR- 2020/06/24
CRDT- 2020/07/17 06:00
PHST- 2020/02/28 00:00 [received]
PHST- 2020/05/13 00:00 [accepted]
PHST- 2020/07/17 06:00 [entrez]
PHST- 2020/07/17 06:00 [pubmed]
PHST- 2020/07/17 06:01 [medline]
PHST- 2020/06/24 00:00 [pmc-release]
AID - 10.3389/fphar.2020.00790 [doi]
PST - epublish
SO  - Front Pharmacol. 2020 Jun 24;11:790. doi: 10.3389/fphar.2020.00790. eCollection 
      2020.