Original Research

Anti-HMGB1 Antibody Decreases Surgery-Induced Upregulation of Necroptosis-Associated Proteins in Aged Rats

Hongkang Zhou , Shuibing Zhang , Yuan Le , Jufang Huang , Jianbin Tong , Wen Ouyang
1Department of Anatomy & Neurobiology, School of Basic Medical Science, 2Postdoctoral Research Station of Basic Medical Science, Central South University, Department of Anesthesiology, Hunan Children’ s Hospital, Department of Anesthesiology, Third Xiangya Hospital, Central South University, Department of Anatomy & Neurobiology, School of Basic Medical Science, Central South University
J Anesth Perioper Med 2018; 5(X): x- xx . Published on Apr 26, 2018 . doi:10.24015/JAPM.2018.0050
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Background: Systemic high mobility group box 1 protein (HMGB1) plays a pivotal role in mediating development and progression of postoperative cognitive dysfunction (POCD). However, the molecular mechanism on how systemic HMGB1 neutralization improves POCD is not fully elucidated. Necroptosis could cause sterile inflammation and negatively associates with the cognitive score in Alzheimer’s disease. Thus we detected the effects of anti-HMGB1 antibody on the necroptosis-associated protein expressions during the POCD of aged rats.
Methods: Aged Sprague-Dawley rats (19-22 months old) were randomly assigned into three groups, (1) control with saline; (2) surgery + immunoglobulin G as control antibody; (3) surgery + HMGB1 neutralizing antibody. A partial hepatolobectomy under sevoflurane anesthesia and analgesia were performed. Immunoglobulin G (1 mg/kg) and HMGB1 neutralizing antibody (1 mg/kg) were injected via tail right before and 6 hours after surgery. The expression of necroptosis-associated proteins (HSP90, CDC37, and RIP3) in the prefrontal cortex of brain was detected by western blot and immunofluorescence. Oxidative stress was measured by dihydroethidium staining.
Results: Systemic administration of anti-HMGB1 antibody decreased the levels of reactive oxygen species (ROS) and reduced the expression of HSP90, CDC37, and RIP3 in prefrontal cortex neurons of brains after surgery (P < 0.05, respectively). Moreover, acetylated HSP90 (ACHSP90) which is a negative regulator of necroptosis was significantly decreased by treatments of anti-HMGB1 neutralization antibody (P < 0.05).
Conclusion: Systemic administration of anti-HMGB1 antibody may improve POCD through reducing reactive oxygen species and decreasing necroptosis in the prefrontal cortex of the aged brain. (Funded by the National Natural Science Foundation of China and Central South University Postdoctoral Foundation in Changsha, China.) 

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