乌司他丁通过SIRT1、PGC-1a调节氧化应激对失血性休克大鼠脑损伤的保护作用

Ulinastatin Regulates Oxidative Stress Through SIRT1 and PGC-1α to Protect Brain Injury in Rats with Hemorrhagic Shock

关键词:  失血性休克  缺血再灌注损伤  乌司他丁  氧化应激反应  沉默信息调节因子  过氧化物酶体增殖物激活受体g共激活因子-1a

Key words:  hemorrhagic shock  ischemia-reperfusion injury  ulinastatin  oxidative stress response  SIRT1  PGC-1α

摘要:

目的 探讨乌司他丁对失血性休克大鼠脑损伤的影响及作用机制。方法 36只♂ SD大鼠随机分为对照组、模型组和观察组，每组12只，对照组给予假手术，模型组造模后不予处理，观察组造模后予以乌司他丁静脉输注。记录造模时采血开始、采血结束、回输开始以及回输结束时的平均动脉压（MAP）、pH、碱剩余（BE）以及乳酸浓度（La）。造模成功24 h后检测海马组织线粒体超氧化物歧化酶（SOD）活性以及丙二醛（MDA）含量，Western blotting测定海马组织中沉默信息调节因子（SIRT1）与过氧化物酶体增殖物激活受体g共激活因子-1a（PGC-1a）蛋白的表达情况。结果 采血开始时和回输结束时各组大鼠MAP无统计学差异；模型组和观察组在采血结束和回输开始时MAP均明显低于对照组（P<0.05）。采血开始时3组大鼠pH值、BE值和La值无统计学差异；与对照组比，采血结束时、回输开始时模型组和观察组pH值降低、BE值降低、La值升高（P<0.05）；回输结束时3组pH值无统计学差异，与对照组比，模型组和观察组BE值降低、La值升高（P<0.05）。海马组织线粒体SOD活性由高到低分别为对照组、观察组和模型组，3组间比较差异具有统计学意义（P<0.05）。3组MDA含量由高到低分别为模型组、观察组和对照组，3组间的差异均具有统计学意义（P<0.05）。Western blotting结果显示，SIRT1、PGC-1a蛋白表达水平由低到高均为对照组、模型组、观察组。结论 乌司他丁可通过促进SIRT1、PGC-1a蛋白在海马组织中的表达，达到抗氧化应激的作用，发挥保护大鼠缺血再灌注脑损伤的效果。

Abstract:

OBJECTIVE To explore the effect and mechanism of ulinastatin on brain injury in rats with hemorrhagic shock. METHODS Thirty-six ♂ SD rats were randomly divided into control group, model group and observation group, 12 rats in each group. The control group was given sham operation, the model group was not treated after modeling, and the observation group was given ulinastatin intravenous infusion after modeling. The mean arterial pressure(MAP), pH, base excess(BE) and lactic acid concentration(La) at the beginning of blood collection, the end of blood collection, the beginning of reinfusion and the end of reinfusion during modeling were recorded. The activity of superoxide dismutase(SOD) and the content of malondialdehyde(MDA) in hippocampus were measured 24 hours after the establishment of the model. The expression of SIRT1 and PGC-1α in hippocampus were measured by Western blotting. RESULTS There was no significant difference in MAP between groups at the beginning of blood collection and at the end of reinfusion. At the end of blood collection and the beginning of reinfusion, the MAP in the model group and the observation group was significantly lower than the control group(P<0.05). There was no statistical difference in pH, BE and La between the three groups at the beginning of blood collection. Compared with the control group, at the end of blood collection and the beginning of reinfusion, the pH, BE decreased, the La increased in the model group and observation group(P<0.05). At the end of reinfusion, there was no statistical difference in pH among the three groups, compared with the control group, the BE decreased, the La increased in the model group and observation group(P<0.05). The activity of SOD in the three groups from high to low were control group, observation group and model group, the difference was statistically significant(P<0.05). The content of MDA in the three groups from high to low were model group, observation group and control group, the difference was statistically significant(P<0.05). Western blotting showed that SIRT1 and PGC-1α protein expression levels were from low to high in the control group, model group and observation group. CONCLUSION Ulinastatin can promote the expression of SIRT1 and PGC-1α protein in hippocampus, achieve the effect of anti oxidative stress, and play the role of protecting the brain injury of ischemia-reperfusion rats.