Effects of Isoflurane and Sevoflurane Anesthesia on Microglia Activation and Neural Stem Cell Proliferation and Differentia-tion in Neonatal Rats and Its Mechanism of Action
Objective To investigate the effects and mechanisms of isoflurane(ISO)and sevoflurane(SEV)inhala-tion anesthesia on the activation of microglia and proliferation and differentiation of neural stem cell(NSC)in neonatal rats.Methods A total of 45 6-day-old rats were divided into control group,ISO group and SEV group by randomized nu-merical table method,with 15 rats in each.All the rats were injected intraperitoneally with 50 mg/kg 5-bromo-2'-de-oxyuridine(BrdU)prior to the onset of anesthesia,and inhaled 30％O2,1.1％ISO+30％O2,2.0％SEV respectively in the order of control group,ISO group and SEV group,continous inhalation for 4 h,and vital signs and arterial blood gas were monitored.After 8 weeks of age,the learning and spatial working memory abilities of the rats were detected by Morris water maze and T-maze experiments;the expression of microglia,NSC proliferation markers and vascular endo-thelial growth factor 2(VEGFR2)pathway-related proteins in brain of the rats were detected by Western blot;the ex-pressions of proliferation and differentiation markers of microglia and NSC in the hippocampus were detected by immuno-fluorescence assay.Results Inhalation of 1.1％ISO or 2.0％SEV for 4 h had no significant effect on vital signs and arterial blood gas in the neonatal rats.Compared with control group,the escape latency and swimming distance of adult rats in ISO group and SEV group increased,the number of crossing platforms and the correct rate of alternate selection decreased(all P＜0.01),protein expression of Nestin and sex determining region Y box 2(Sox2)and phosphorylated-VEGFR2(p-VEGFR2)/VEGFR2 ratio decreased in brain tissues,the protein expressions of recombinant integrin alpha M(CD11b),interleukin 6(IL-6)and tumor necro-sis factor alpha(TNF-α)increased(all P＜0.05),the proportion of Nestin+/BrdU+,Sox2+/BrdU+,glial fibrillary a-cidic protein(GFAP)+/Sox2+,doublecortin(DCX)+/BrdU+,Reelim+/BrdU+and neuronal nuclei(NeuN)+/BrdU+cells decreased,the proportion of lonized calcium-binding adapter molecule 1(IBA1)+cells increased(all P＜0.05).Compared with ISO group,the escape latency and swimming distance of rats in SEV group increased,the number of crossing platforms decreased and the correct rate of alternate selection increased(all P＜0.05);the protein expression of Nestin and Sox2 increased,the proportion of Sox2+/BrdU+,GFAP+/Sox2+and Reelin+/BrdU+cells increased(all P＜0.05)and there were no significant differences in the expressions of p-VEGFR2/VEGFR2 ratio,CD11b,IL-6 and TNF-α protien,and the proportion of Nestin+/BrdU+,DCX+/BrdU+and NeuN+/BrdU+cells between the two groups(P＞0.05).Conclusion ISO and SEV may inhibit NSC proliferation,differentiation and neurogenesis by promoting mi-croglial cell activation and activating the VRGFR2 signaling pathway,leading to cognitive dysfunction in neonatal rats.
NETL
NSTL
万方数据
