异氟醚预处理对兔局灶性脑缺血再灌注时降钙素基因相关肽和NF—κB的影响

Effec.t of isoflurane preconditioning on calcitonin gene-related peptide and NF-kappa B following local cerebral ischemia/reperfusion in rabbits

目的探讨异氟醚预处理对兔局灶性脑缺血再灌注时降钙素基因相关肽（CGRP）和NF-κB水平的影响。方法新西兰纯系家兔54只，雌雄不拘，体重2．0—2．5kg，采用随机数字表法，将其随机分为3组（n=18）：假手术组（S组）、脑缺血再灌注组（I／R组）和异氟醚预处理（I组）。麻醉下气管内插管，机械通气，S组和I／R组静脉输注咪达唑仑维持麻醉；I组吸入1．4％异氟醚30min后洗脱10min进行异氟醚预处理，然后制备脑缺血再灌注损伤模型，在脑缺血再灌注损伤过程中静脉输注咪达唑仑，3组静脉输注芬太尼和维库溴铵。I／R组和I组采用线栓法制备局灶性脑缺血再灌注损伤模型，于缺血2h时进行再灌注。分别于麻醉前和再灌注即刻、1h、2h、3h、4h、5h时取耳中央动脉血样，测定血浆CGRP浓度，各时点取完血样后立即处死动物，测定脑组织神经元NF．加活性及其表达。结果与S组比较，I／R组血浆CGRP浓度、脑组织神经元NF-κB活性升高，脑组织NF-κB表达上调（P〈0．05）；与I／R组比较，I组血浆CGRP浓度升高，脑组织神经元NF-κB活性降低，脑组织NF-κB表达下调（P〈0．05）。结论异氟醚预处理减轻兔脑缺血再灌注损伤的机制与促进CGRP释放及抑制神经元NF-κB功能有关。

Objective To investigate the effect of isoflurane preconditioning on calcitonin gene-related peptide （CGRP） and NF-kappa B following local cerebral ischemia/reperfusion （I/R） in rabbits. Methods Fiftyfour adult New Zealand white rabbits of both sexes weighing 2.0-2.5 kg were randomly divided into three groups （n = 18 each） ： sham operation group （group S）, group I/R andisoflurane preconditioning group（group I）. After anesthesia induction with intramuscular injection of ketamine 70 mg/kg and scopolamine 0. 006 mg/kg and maintenance of anesthesia with intravenous injection of midazolam 0.1 mg/kg, fentanyl 0.01 mg/kg and vecuronium 0.1 mg/kg, endotracheal intubation was performed and mechanical ventilation was employed. In groups I/R and S, midazolam at 0.1 mg· kg^-1 · h^-1 was infused through the left ear vein. After the rabbits in group i inhaling 1.4% isoflurane for 30 minutes, which was then eluted for 10 minutes, local cerebral ischemia was made in groups I/R and I with thread ligation method, and reperfusion was made 2 hours later, simttItaneously midazolam at 0.1 mg· kg^-1 · h^-1 was injected. All the rabbits in three groups were infused with fentanyl at 0.05 mg· kg^-1 · h^-1 and vecu- ronium at 0.10 mg· kg^-1 · h^-1 . After blood samples were collected from the central artery of the ear for determination of plasma CGRP before anesthesia, immediately before reperfusion, and t, 2, 3 , 4, and 5 h of reperfusion, all the animals were sacrificed at the corresponding time point＇s and brain tissues were obtained for determination of NF-κB activity and its expression with Western blotting and immunohistochemistry staining. Results The plasma concentration of CGRP, the activity and expression of NF-κB were higher in group I/R than in group S （ P 〈 0.05）. The plasma concentration of CGRP was higher and the activity and expression of NF-κB were lower in group I than in group I/R （ P 〈 0.05 ）. Conclusion Isoflurane preconditioning can reduce local cerebral I/R injury in rabbits through promoting CGRP release and inhibiting NF-κB function.