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SAHA預(yù)處理對初進(jìn)高原致死性失血性休克大鼠的救治作用及肺保護(hù)作用的研究

發(fā)布時間:2018-07-04 12:40

  本文選題:致死性失血性休克 + SAHA ; 參考:《蘭州大學(xué)》2013年碩士論文


【摘要】:第一部分 SAHA預(yù)處理對初進(jìn)高原致死性失血性休克大鼠早期生存率的影響 目的探討辛二酰苯胺異羥肟酸(SAHA, Suberoylanilide Hydroxamic Acid)預(yù)處理對初進(jìn)高原致死性失血性休克大鼠早期生存率的影響。 方法36只初進(jìn)高原雄性SD大鼠(體重=260±20g),采用隨機(jī)數(shù)字法分為3組(n=12):假手術(shù)組(Sham組),生理鹽水(Normal Saline, NS)預(yù)處理組(NS組),SAHA預(yù)處理組(SAHA組)。Sham組麻醉后單純手術(shù)操作,不給予失血處理;NS組和SAHA組于實(shí)驗(yàn)前24h和失血前經(jīng)皮下分別給予0.25ml NS或溶于等量NS的SAHA(7.5mg/kg)溶液預(yù)處理,制備初進(jìn)高原大鼠致死性失血性休克模型后,各組持續(xù)監(jiān)測平均動脈壓(MAP)至休克后60min。失血前后及休克后60min三個時間點(diǎn)行動脈血?dú)夥治。觀察大鼠180min,記錄每只大鼠死亡時間,判斷大鼠60min、120min和180min生存率。 結(jié)果SAHA組大鼠休克后60min、120min和180min生存率均顯著高于NS組(P0.05)。休克15mi n到60min,與NS組比較,SAHA組大鼠休克后MAP、動脈血PH、PaO和BE值顯著升高(P0.05),Lac濃度顯著降低(P0.05),而PaCO無明顯變化。 結(jié)論SAHA預(yù)處理可顯著提高初進(jìn)高原致死性失血性休克大鼠早期生存率,維持失血后血流動力學(xué)的相對穩(wěn)定。 第二部分 SAHA預(yù)處理對初進(jìn)高原致死性失血性休克大鼠肺臟保護(hù)作用的研究 目的探討辛二酰苯胺異羥肟酸(SAHA,Suberoylanilide Hydroxamic Acid)預(yù)處理對初進(jìn)高原致死性失血性休克大鼠的肺保護(hù)作用,初步探索其可能機(jī)制。 方法36只初進(jìn)高原雄性SD大鼠(體重:260±20g),采用隨機(jī)數(shù)字法分為3組(n=12):假手術(shù)組(Sham組),生理鹽水(Normal Saline,NS)預(yù)處理組(NS組),SAHA預(yù)處理組(SAHA組)。Sham組麻醉后單純手術(shù)操作,不給予失血處理;NS組和SAHA組于實(shí)驗(yàn)前24h和失血前兩次經(jīng)皮下分別給予0.25ml NS或溶于等量NS的SAHA(7.5mg/kg)溶液預(yù)處理。制備初進(jìn)高原大鼠致死性失血性休克模型,觀察大鼠180min,到時處死大鼠(存活時間未滿180min者于死亡即刻)開胸于冰面上取肺臟,觀察各組大鼠肺組織病理學(xué)變化,計算肺損傷評分、肺濕干質(zhì)量比(W/D),檢測肺組織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的表達(dá)量。 結(jié)果與NS組比較,SAHA組大鼠肺臟組織病理學(xué)變化較輕微,且肺損傷評分、肺濕干質(zhì)量比、MDA含量、MPO活性、TNF-α含量和TNF-α/IL-10比值明顯降低(P0.05),SOD活性、IL-10含量和Ac-H3K9表達(dá)量顯著升高(P0.05)。 結(jié)論SAHA預(yù)處理對初進(jìn)高原致死性失血性休克大鼠肺臟具有一定的保護(hù)作用,該作用可能與SAHA預(yù)處理提高肺細(xì)胞組蛋白的乙;,繼而增強(qiáng)肺臟抗炎/抗氧化能力的作用有關(guān)。
[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 鹵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 鹵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- 偽 / 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- 偽 and TNF- 偽 / 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.
【學(xué)位授予單位】:蘭州大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2013
【分類號】:R459.7

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 檀瓊;劉全海;;組蛋白去乙;敢种苿┑难芯窟M(jìn)展[J];世界臨床藥物;2010年10期

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本文編號:2096111

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