Protective effect of sevoflurane postconditioning against cerebral ischemia/reperfusion injury in rats
Objective To investigate the protective effect of sevoflurane postconditioning against cerebral ischemia/reperfusion(I/R)injury in rats and its mechanism of action.Methods A total of 80 specific pathogen-free healthy adult male Sprague-Dawley rats were selected and randomly divided into sham-operation group(S group),cerebral I/R group(I/R group),cerebral I/R+sevoflurane postconditioning group(ISP group),and cerebral I/R+sevoflurane postconditioning+nuclear factor ery-throid 2-related factor 2(Nrf2)inhibitor group(ISPB group),with 20 rats in each group.All rats except those in the S group were used to establish a rat model of cerebral I/R injury using the suture method for occlusion of the middle cerebral artery for 2 h,fol-lowed by reperfusion for 24 h,and for the rats in the S group,threading was performed below the middle cerebral artery without ligation.The rats in the ISP group were given inhalation of 3％sevoflurane immediately after reperfusion for 30 min,and those in the ISPB group were given intraperitoneal injection of the Nrf2 inhibitor brusatol(2 mg/kg)at 30 min before ischemia in addition to the treatment in the ISP group.After successful modeling,neurological deficit score was used to eval-uate the degree of neuro-logical impairment.Left ventricular blood samples and pathological sections of brain tissue were obtained,and 2,3,5-triphenyltet-razolium chloride staining was used to determine the percentage of cerebral infarct volume;enzyme-linked immunosorbent assay was used to measure the serum levels of inflammatory factors(interleukin-1β[IL-1β]and tumor necrosis factor-α[TNF-α])and oxidative stress-related factors(malondialdehyde[MDA]and superoxide dismutase[SOD]);Western blotting was used to mea-sure the expression of apoptosis-related proteins(B-cell lymphoma-2[Bcl-2],Bcl-2 related x[Bax],and Caspase-3)and Nrf2 sig-naling pathway-related proteins(Nrf2 and heme oxygenase-1[HO-1])in brain tissue;immunofluorescence assay was used to measure the expression of Nrf2 inside and outside the nucleus of brain tissue cells.Results Compared with the I/R group,the ISP group had significant reductions in neurological deficit score,the percentage of cerebral infarct volume,the serum levels of IL-1β,TNF-α,and MDA,and the levels of Bax and Caspase-3 in brain tis-sue(t=5.76-18.39,P＜0.05)and significant increases in the serum level of SOD and the levels of Nrf2,HO-1,and Bcl-2 in brain tissue(t=5.73-14.08,P＜0.05),as well as a significant increase in Nrf2 immunofluorescence intensity.Compared with the ISP group,the ISPB group had significant increases in neurological deficit score,the percentage of cerebral infarct volume,the se-rum levels of IL-1β,TNF-α,and MDA,and the levels of Bax and Caspase-3 in brain tissue(t=3.06-8.19,P＜0.05)and signifi-cant reductions in the serum level of SOD and the levels of Nrf2,HO-1,and Bcl-2 in brain tissue(t=2.67-9.01,P＜0.05),as well as a reduction in Nrf2 immunofluorescence intensity.Conclusion Sevoflurane postconditioning can inhibit oxidative stress,inflammatory response,and cell apoptosis by activating the Nrf2 signaling pathway,thereby alleviating cerebral I/R injury in rats.
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