| [Objective] Kidney ischemia reperfusion injury (KIRI) is an important pathogeny of early-stage kidney failure after operation. KIRI is also one of the key factors in early-stage functional recovery and chronic disfunction of transplanted kidney. KIRI can cause decreasing in the number of renal parenchymal cells, atrophy of renal tissue structure and failure of kidney function. Sevoflurane has been widely applied in clinical practice with such advantages as quickly discharged and less airway stimulation. It is reported that2.2%sevoflurane has protective effect in heart, brain and kidney. Furthermore, sevoflurane has an anti-inflammatory effect in kidney proximal tubule cells and tubular epithelial cells. Heme oxygenase-1is inducible expression of heme oxygenase, it is also known as heat shock protein-32(HSP-32). HO-1exists in microsome of most type tissues. It belongs to antioxidases that can be easily induced by several factors such as stress and hypoxemia to play an important role as antioxidant, anti-inflammatory and anti-apoptosis in cell protection. The study aims to investigate the effect and possible mechanism of sevoflurane pretreatment on KIRI in rats in the perspective of oxidative stress, inflammatory response and apoptosis, and whether this effect can be interfered by different sevoflurane inhalational concentrations. Hope to provide experimental evidence for choosing appropriate anesthetic and dose in clinical practice.[Methods] Fifty pathogen-free male SD rats weighing220-260g were randomized into5groups (n=10each):control group (group C); ischemia-reperfusion injury group (group I/R);2.2%sevoflurane group (group S1);2.8%sevoflurane group (group S2) and3.3%sevoflurane group (group S3).KIRI was performed by clamping the left renal pedicle for45min in I/R and in Si,S2,S3.In group S1, S2, S3, inhalation of2.2%,2.8%,3.3%sevoflurane in O2was started at30min before operation and maintained throughout the experiment respectively. Venous blood samples were taken at3h of reperfusion for determination of serum BUN and Cr concentrations. The animals were then sacrificed and the left kidneys were removed for microscopic pathology examination (by HE stain), detection of apoptosis(by TUNEL), measurement of NF-KB,TNF-α,IL-8,ICAM-l,MDA content and SOD activity, determination of heme oxygen-1(HO-1) mRNA and protein expression(by RT-PCR and Western blot)[Results] Compared with group C, in group I/R and group S1,S2,S3,serum BUN and Cr concentrations, the severity of necrosis of renal proximal convoluted tubules, apoptotic index,NF-KB,TNF-α,IL-8,ICAM-1,MDA content,HO-1mRNA and HO-1protein were significantly increased and SOD activity were decreased(P<0.05).Compared with group I/R, in group S1,S2,S3, serum BUN and Cr concentrations, the severity of necrosis of renal proximal convoluted tubules, apoptotic index, NF-κ B,TNF-a,IL-8,ICAM-1,MDA content were decreased, SOD activity and HO-1mRNA were increased(P<0.05).There were no significant differences in HO-1protein expression between group S1,group S2,group S3and group I/R(P>0.05).Compared with group S2,NF-κB,TNF-α,ICAM-1content were increased in group Si,while in group S3, these indices were decreased(P<0.05). There were no significant differences in the severity of necrosis of renal proximal convoluted tubules, apoptotic index,IL-8,MDA content, SOD activity and HO-1mRNA between group S1,group S2and group S3(P>0.05).[Conclusions] Sevoflurane pretreatment can protect kidney against KIRI by anti-oxidization, reducing inflammatory factor release and attenuating cell apoptosis. Up-regulation of HO-1mRNA expression may be involved in the mechanism. Different concentrations (2.2%,2.8%,3.3%) of sevoflurane play a role in reducing inflammatory factor release, but not in anti-oxidization and attenuating cell apoptosis. |
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