SAHA预处理对初进高原致死性失血性休克大鼠的救治作用及肺保护作用的研究

发布时间：2018-07-04 12:40

本文选题：致死性失血性休克 + SAHA　；参考：《兰州大学》2013年硕士论文

【摘要】：第一部分 SAHA预处理对初进高原致死性失血性休克大鼠早期生存率的影响目的探讨辛二酰苯胺异羟肟酸(SAHA, Suberoylanilide Hydroxamic Acid)预处理对初进高原致死性失血性休克大鼠早期生存率的影响。方法36只初进高原雄性SD大鼠(体重=260±20g),采用随机数字法分为3组(n=12)：假手术组(Sham组),生理盐水(Normal Saline, NS)预处理组(NS组),SAHA预处理组(SAHA组)。Sham组麻醉后单纯手术操作,不给予失血处理；NS组和SAHA组于实验前24h和失血前经皮下分别给予0.25ml NS或溶于等量NS的SAHA(7.5mg/kg)溶液预处理,制备初进高原大鼠致死性失血性休克模型后,各组持续监测平均动脉压(MAP)至休克后60min。失血前后及休克后60min三个时间点行动脉血气分析。观察大鼠180min,记录每只大鼠死亡时间,判断大鼠60min、120min和180min生存率。结果SAHA组大鼠休克后60min、120min和180min生存率均显著高于NS组(P0.05)。休克15mi n到60min,与NS组比较,SAHA组大鼠休克后MAP、动脉血PH、PaO和BE值显著升高(P0.05),Lac浓度显著降低(P0.05),而PaCO无明显变化。结论SAHA预处理可显著提高初进高原致死性失血性休克大鼠早期生存率,维持失血后血流动力学的相对稳定。第二部分 SAHA预处理对初进高原致死性失血性休克大鼠肺脏保护作用的研究目的探讨辛二酰苯胺异羟肟酸(SAHA,Suberoylanilide Hydroxamic Acid)预处理对初进高原致死性失血性休克大鼠的肺保护作用,初步探索其可能机制。方法36只初进高原雄性SD大鼠(体重：260±20g),采用随机数字法分为3组(n=12)：假手术组(Sham组),生理盐水(Normal Saline,NS)预处理组(NS组),SAHA预处理组(SAHA组)。Sham组麻醉后单纯手术操作,不给予失血处理；NS组和SAHA组于实验前24h和失血前两次经皮下分别给予0.25ml NS或溶于等量NS的SAHA(7.5mg/kg)溶液预处理。制备初进高原大鼠致死性失血性休克模型,观察大鼠180min,到时处死大鼠(存活时间未满180min者于死亡即刻)开胸于冰面上取肺脏,观察各组大鼠肺组织病理学变化,计算肺损伤评分、肺湿干质量比(W/D),检测肺组织SOD活性、MDA含量、MPO活性、IL-10含量、TNF-α含量、TNF-α/IL-10比值及Ac-H3K9的表达量。结果与NS组比较,SAHA组大鼠肺脏组织病理学变化较轻微,且肺损伤评分、肺湿干质量比、MDA含量、MPO活性、TNF-α含量和TNF-α/IL-10比值明显降低(P0.05),SOD活性、IL-10含量和Ac-H3K9表达量显著升高(P0.05)。结论SAHA预处理对初进高原致死性失血性休克大鼠肺脏具有一定的保护作用,该作用可能与SAHA预处理提高肺细胞组蛋白的乙酰化水平,继而增强肺脏抗炎／抗氧化能力的作用有关。
[Abstract]:Part I effects of SAHA preconditioning on early survival rate of rats with fatal hemorrhagic shock at high altitude objective to investigate the effect of SAHA (Suberoylanilide Hydroxamic Acid) preconditioning on fatal loss at high altitude Effect of early survival rate in rats with hemorrhagic shock. Methods Thirty-six male Sprague-Dawley rats (body weight 260 卤20g) were randomly divided into three groups (n = 12): sham group (sham group), normal Saline (NS) preconditioning group (NS group), SAHA preconditioning group (SAHA group) .Sham group (n = 36) were divided into three groups: sham group (sham group), normal Saline (NS) preconditioning group (NS group) and SAHA preconditioning group (SAHA group). NS group and SAHA group were pretreated subcutaneously with 0.25ml NS or SAHA (7.5mg/kg) solution at 24 h before experiment and before blood loss, respectively. After the model of lethal hemorrhagic shock was established in rats at high altitude, the mean arterial pressure (map) was continuously monitored from 60 min after shock in each group. Arterial blood gas was analyzed at three time points of 60min before and after hemorrhage and shock. The time of death of each rat was recorded and the survival rate of 60 min, 120 min and 180min were determined. Results the survival rate of 120 min and 180min in SAHA group was significantly higher than that in NS group (P0.05). After shock, compared with NS group, the arterial blood PHPAO and be were significantly increased (P0.05) and the concentration of Lac was significantly decreased (P0.05), but Paco did not change significantly. Conclusion SAHA pretreatment can significantly improve the early survival rate and maintain the relative stability of hemodynamics after hemorrhagic shock at high altitude. The second part of the study on the protective effect of SAHA preconditioning on the lungs of rats with fatal hemorrhagic shock at high altitude objective to investigate the effects of SAHAHAA Suberoylanilide Hydroxamic Acid pretreatment on the fatal loss of lung in rats with neonatal hemorrhagic shock at high altitude. Pulmonary protective effects of hemorrhagic shock rats, The possible mechanism was preliminarily explored. Methods Thirty-six male Sprague-Dawley rats (weight: 260 卤20g) were randomly divided into three groups: sham group (sham group), normal saline pretreatment group (NS group) and SAHA preconditioning group (SAHA group). NS group and SAHA group were pretreated subcutaneously with 0.25ml NS or SAHA (7.5mg/kg) solution dissolved in NS at 24 h before experiment and before blood loss. The lethal hemorrhagic shock model was made in rats at high altitude, and the rats were observed for 180 minutes. Then the rats were killed (those whose survival time was less than 180min at the moment of death) and the lungs were taken from the ice surface. The pathological changes of lung tissue were observed in each group. Lung injury score, lung wet / dry weight ratio (W / D), SOD activity, MDA content, MPO activity and IL-10 content, TNF- 伪 / IL-10 ratio and Ac-H3K9 expression were measured. Results compared with NS group, the histopathological changes of lung in SAHA group were slight, and the lung injury score, lung wet dry weight ratio, MPO activity, TNF- 伪 and TNF- 伪 / IL-10 ratio were significantly decreased (P0.05), and the activity of SOD and the expression of Ac-H3K9 were significantly increased (P0.05). Conclusion SAHA pretreatment has a protective effect on lungs of rats with fatal hemorrhagic shock at high altitude, which may be related to the enhancement of histone acetylation in lung cells by SAHA preconditioning. It is related to the enhancement of anti-inflammatory / anti-oxidation ability of lung.
【学位授予单位】：兰州大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R459.7

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