The role of PPARγ phosphorylation in the neuroprotective effect of dexmedetomidine through the hippocampal CA1 region during rat extracorporeal circulation
The role of PPARγ phosphorylation in the neuroprotective effect of dexmedetomidine through the hippocampal CA1 region during rat extracorporeal circulation
Objective To investigate the role of PPARγ phosphorylation in the neuroprotective effect of dexmedetomidine during rat extracorporeal circulation.Methods Thirty-six adult healthy male SPF-grade SD rats weighing 350 to 450 g were randomly divided into three groups(n=12 each):Sham group(S group),Extracorporeal Circulation group(C group),and Dexmedetomidine group(D group).The S group underwent tracheal intubation under pentobarbital sodium anesthesia,with catheterization of the right internal jugular vein and bilateral femoral arteries without extracorporeal circulation.The C group underwent the same procedures as the S group but with the establishment of a rat extracorporeal circulation model for 2 hours.The D group received a continuous intravenous infusion of dexmedetomidine injection at a rate of 5 μg/(kg·h)15 minutes before and during the 2-hour extracorporeal circulation via the right internal jugular vein.Saline was infused at a constant volume during catheterization or perfusion in the S and C groups.After 2 hours of catheterization or perfusion,specimens were collected.Hematoxylin and eosin staining were used to observe pathological changes in the hippocampal tissue.Enzyme-linked immunosorbent assay was employed to measure plasma concentrations of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and central nervous system-specific protein(S100β).Western blotting was conducted to assess the protein expression of Bcl-2,Bax,Cleaved Caspase-3,PPARγ,and p-PPARγ in the hippocampal tissue.Immunohistochemistry staining was performed to determine the number of positive cells expressing p-PPARy protein in the hippocampal tissue.Results In the S group,the hippocampal CA1 region cells showed intact morphology.In the C group,the hippocampal CA1 region cells were severely damaged,exhibiting nuclear condensation,widened gaps,and visible cell death.In the D group,the damage was less severe,with only a small amount of cell death observed in the hippocampal CA1 region.Levels of TNF-α,IL-6,and S100β in the C and D groups were higher than those in the S group(P＜0.05).Compared with the C group,levels of TNF-α,IL-6,and S100β in the D group were reduced(P＜0.05).Relative expression levels of Bcl-2 protein in the hippocampal tissue were lower in the C and D groups than in the S group(P＜0.05),while expression levels of Bax,Cleaved Caspase-3,and p-PPARγ/PPARγ proteins were higher(P＜0.05).Compared with the C group,the relative expression of Bcl-2 protein in the hippocampal tissue increased in the D group(P＜0.05),while the expression levels of Bax,Cleaved Caspase-3,and p-PPARγ/PPARγ proteins decreased(P＜0.05).Conclusion The neuroprotective effect of dexmedetomidine during rat extracorporeal circulation may be associated with the inhibition of PPARγphosphorylation.
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