The Protective Effects And Mechanism Of α7 Nicotinic Acetylcholine Receptors Agonist On Brain Injury Induced By CPB

Objective : To investigate the protective effect of α7 nicotinic acetylcholine receptor(α7n ACh R)agonist against brain injury induced by cardiopulmonary bypass(CPB)and the mechanism of the protective roll.Methods:96 adult male SD rats,aged 5-6 months,weighing 350-400 g,were randomly divided into 4 groups(n = 24 each): sham operation group(group S),CPB operation group(group C),CPB+PHA group(group P)and CPB+MLA+PHA group(group M).The animals were anesthetized with 2.5% sevoflurane in O2/air(1:1)and intraperitoneal 10% chloral hydrate 350 mg/kg before intubation and mechanical ventilation.The cauda and jugular arteries and jugular vein were cannulated.CPB was performed for 60 min,except for group S.PHA568487(0.8mg/kg)or MLA(6mg/kg)+ PHA568487(0.8mg/kg)were administered intraperitoneally 30 min prior to CPB in groups P and M respectively,while the equal volume of normal saline was added in groups S and C.Each group was set up four time points: T0(right before CPB),T1((right after CPB),T2(2 h after CPB),T3(6 h after CPB).Each group was randomly assigned 6 rats for each time point.The animals from each time point were sacrificed for brain sample after serum samples were collected.The serum S-100β and tumor necrosis factor-α(TNF-α)was detected by ELISA.Extent of brain damage such as the morphological changes and cell apoptosis was observed by HE staining.Nuclear factor-κB(NF-κB)protein expression was detected by Western blot.Results:Compared with group S,the levels of plasma TNF-α、S-100β and the expression of NF-κB protein in brain tissue were increased at T1-3 in group C,P,M(p < 0.05).Compared with group C,the levels of plasma TNF-α、S-100β and the expression of NF-κB protein in brain tissue were decreased in group P(p < 0.05),while the levels of above index in group M were no statistically difference(p > 0.05).The histomorphology damage of hippocampus in group M at T3 was the most seriously,while that in group S was lightest.Compared with group C,the histomorphology damage of hippocampus in group P was less seriously.Conclusins:1.α7n ACh Rs agonist can protects brain injury induced by CPB.2.α7n ACh Rs agonist protects brain injury possibly by deceasing NF-κB activation,suppressing cytokine production in rat.