The Role Of NF-κB In Immunodepression After Cerebral Infarction

Background:The treatment of stroke is a huge challenge in neurological field. Globally, stroke is the second leading cause of death in those> 60 years and the fifth leading cause of death in people aged 15 to 59 years old. In addition, China has 2.5 million new stroke cases each year. Stroke,malignant tumor and cardiovascular system disease are three major causes of death, the first cause of mortality in patients with stroke is infection. The studies have shown that the damage of central nervous system can make immunodeppression, leading to infection. Although it is unclear that the relationship of central nervous system and immune system, hypothalamic-pituitary-adrenal axis and sympathetic nervous system play roles in this process.Now a research indicates negative effects of cAMP on NF-κB activity.The decrease of NF-κB activity can break the balance of Inflammatory cytokines, which can lead to immunodepression. Stroke-induced immunodepression syndrome is a research focus in recent years. My study discuss the relationship of cAMP, PKA and NF-κB in immunodepression after cerebral infarction.Objective:To investigate the changes of cAMP, PKA and NF-κB in immunodepression after cerebral infarction.Methods:Our study has four groups:the sham operation group, the MCAO group, the MCAO+propranolol group, the sham+isopropyl adrenaline group.Every group has eight rats. In the MCAO+propranolol group, we use intraperitoneal injection of sympathetic nerve inhibitors propranolol (10 mg/kg) at 2h,14h,26h,38h,50h,62h after model was inducted.At the same time, we use intraperitoneal injection of Sympathetic nerve agonist isopropyl adrenaline(10 mg/kg) at 2h,14h,26h,38h,50h,62h after sham operation was inducted in isopropyl adrenaline group.After 72 hours,we collect the heart blood 5 ml and remove their spleens.Blood is placed for half an hour and is centrifugalled for ten minutes at 3700r/min under the condition of 4 temperature.We retain these serums. A double-antibody sandwich enzyme-linked inmatmosorbent assay was used to detect the levels of serum proinflannnatory cytokine Tumor necrosis factor-α (TNF-α) and anti-inflammatory cytokines interleukin-10 (IL-10). A competitive enzyme-linked immunosorbent assay was used to detect the levels of cyclic adenosine monophosphate (cAMP) and Protein kinase A(PKA) of the spleens, besides, a western blot was used to detect the levels of nuclear factor κB (NF-κB p65).Results:Comparing with the sham operation group, the levels of cAMP and PKA in the other groups were higher but the levels of NF-κB p65 were lower. The levels of pro inflammatory cytokines TNF-α were increased significantly (P<0.01) except the group of the sham+isopropyl adrenaline (P<0.05) than those in the sham operation, at the same time, the levels of anti-inflammatory cytokines IL-10 were decreased significantly(P<0.01). Comparing with the MCAO group, the IL-10,cAMP and PKA in the MCAO+propranolol group and the sham+isopropyl adrenaline group were lower, the TNF-α and NF-κB in the MCAO+propranolol group and isopropyl adrenaline group were higher. Comparing with the MCAO+propranolol group,the cAMP and PKA in the sham+isopropyl adrenaline group were lower, the NF-kB p65 has no difference.Conclusions:cAMP and PKA were increased, NF-κB p65 were decreased in spleens of rats after cerebral infarction.These can break the balance of serum proinflannnatory and anti-inflammatory cytokines which lead to immunodepression.