PMID- 32558672
OWN - NLM
STAT- MEDLINE
DCOM- 20210813
LR  - 20221005
IS  - 1473-558X (Electronic)
IS  - 0959-4965 (Print)
IS  - 0959-4965 (Linking)
VI  - 31
IP  - 12
DP  - 2020 Aug 12
TI  - Magnesium sulfate ameliorates sepsis-induced diaphragm dysfunction in rats via 
      inhibiting HMGB1/TLR4/NF-kappaB pathway.
PG  - 902-908
LID - 10.1097/WNR.0000000000001478 [doi]
AB  - BACKGROUND: Diaphragm dysfunction could be induced by sepsis with subsequent 
      ventilatory pump failure that is associated with local infiltration of 
      inflammatory factors in the diaphragm. It has been shown that the administration 
      of anticonvulsant agent, magnesium sulfate (MgSO4) could decrease systematic 
      inflammatory response. We recently reported that MgSO4 could inhibit macrophages 
      high mobility group box 1 (HMGB1) secretion that confirms its anti-inflammatory 
      properties. Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-kappaB) signal 
      pathway appears to be involved in the pathology of septic experimental animal's 
      inflammatory response and involve in the pathogenic mechanisms of sepsis-induced 
      diaphragm dysfunction. Thus, in this study, we are aiming to explore whether 
      MgSO4 could ameliorate sepsis-induced diaphragm dysfunction via TLR4/NF-kappaB 
      pathway in a rodent model with controlled mechanical ventilation (CMV) and 
      subsequent septic challenge. METHODS: Rats were randomly assigned into (1) 
      control group: having an identical laparotomy but without ligation or puncture in 
      the cecum; (2) CLP group: cecal ligation and puncture (CLP) with continuous 
      saline infusion; (3) CLP + MgSO4 group: CLP with continuous MgSO4 administration; 
      and (4) MgSO4 group: a sham surgery with MgSO4 administration. After surgery, all 
      rats were submitted to CMV for 18 h. After completion of the study protocol, 
      blood inflammatory cytokine/chemokine was detected by ELISA, as well as diaphragm 
      contractility, TLR4, NF-kappaB (p65), phospho-NF-kappaB (p65) and HMGB1 protein 
      expression. RESULTS: The level of inflammatory cytokine/chemokine includes 
      interleukin-6, monocyte chemoattractant protein-1 (MCP-1), macrophage 
      inflammatory protein-2 (MIP-2) and HMGB1 in blood were significantly increased at 
      18-h post-CLP compared with the control group. We found that rats in the CLP 
      group had substantial diaphragm dysfunction with a distinct downshift of the 
      force-frequency curve. Furthermore, expression of HMGB1, TLR4, NF-kappaB (p65) and 
      phospho-NF-kappaB (p65) in diaphragm were significantly increased in the CLP group. 
      In contrast, MgSO4 attenuated the septic inflammation reaction in diaphragm and 
      serum and preserved diaphragm function. CONCLUSION: MgSO4 protects against 
      sepsis-induced diaphragm dysfunction. This may be associated with its 
      anti-inflammatory effect on HMGB1/TLR4/NF-kappaB signal pathway.
FAU - Jiang, Jihong
AU  - Jiang J
AD  - Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong 
      University School of Medicine, Shanghai.
FAU - Chen, Qi
AU  - Chen Q
AD  - Department of Anesthesiology, Chongqing University Cancer Hospital, Chongqing, 
      China.
FAU - Chen, Xia
AU  - Chen X
AD  - Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong 
      University School of Medicine, Shanghai.
FAU - Li, Jinbao
AU  - Li J
AD  - Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong 
      University School of Medicine, Shanghai.
FAU - Li, Shitong
AU  - Li S
AD  - Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong 
      University School of Medicine, Shanghai.
FAU - Yang, Bin
AU  - Yang B
AD  - Department of Anesthesiology, Chongqing University Cancer Hospital, Chongqing, 
      China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Neuroreport
JT  - Neuroreport
JID - 9100935
RN  - 0 (HMGB1 Protein)
RN  - 0 (NF-kappa B)
RN  - 0 (Tlr4 protein, rat)
RN  - 0 (Toll-Like Receptor 4)
RN  - 7487-88-9 (Magnesium Sulfate)
SB  - IM
MH  - Animals
MH  - Cecum/metabolism
MH  - Diaphragm/*drug effects/metabolism/physiopathology
MH  - HMGB1 Protein/metabolism
MH  - Inflammation/*complications
MH  - Macrophages/drug effects
MH  - Magnesium Sulfate/*pharmacology
MH  - NF-kappa B/metabolism
MH  - Rats, Sprague-Dawley
MH  - Sepsis/*complications/physiopathology
MH  - Signal Transduction/physiology
MH  - Toll-Like Receptor 4/metabolism
PMC - PMC7368847
COIS- There are no conflicts of interest.
EDAT- 2020/06/20 06:00
MHDA- 2021/08/14 06:00
PMCR- 2020/07/19
CRDT- 2020/06/20 06:00
PHST- 2020/06/20 06:00 [pubmed]
PHST- 2021/08/14 06:00 [medline]
PHST- 2020/06/20 06:00 [entrez]
PHST- 2020/07/19 00:00 [pmc-release]
AID - 00001756-202008020-00009 [pii]
AID - 10.1097/WNR.0000000000001478 [doi]
PST - ppublish
SO  - Neuroreport. 2020 Aug 12;31(12):902-908. doi: 10.1097/WNR.0000000000001478.