本文選題：急性肺損傷 + 烏司他丁�。� 參考：《第二軍醫(yī)大學》2014年碩士論文

【摘要】：急性肺損傷（Acute Lung Injury，ALI）是繼發(fā)于嚴重創(chuàng)傷、感染、休克和大手術后，以呼吸窘迫和頑固性低氧血癥為臨床特征的綜合征，急性肺損傷是多臟器功能障礙綜合征(multiple organ dysfunction syndrome, MODS)在肺部的突出表現(xiàn)，急性呼吸窘迫綜合征（Acute respiratorydistress syndrome，ARDS）是其最嚴重的表現(xiàn)形式。急性肺肺損傷的發(fā)病率為每年38/10萬，近年來有逐漸增高的趨勢，盡管采取了很多措施，急性肺損傷的死亡率仍高達32%-50%，高遷移率族蛋白B1（Highmobility group box1protein，HMGB1）是一種晚期炎癥介質(zhì)，同時也是一種促炎細胞因子，能夠介導炎癥反應并保持級聯(lián)擴大作用，其生物學特性跟多種疾病的發(fā)病機制有很高的關聯(lián)性，越來越多的研究證實，炎性因子在急性肺損傷的發(fā)生發(fā)展中起著重要作用；烏司他�。║linastatin，UTI）為一種蛋白酶抑制劑，早期用于急性胰腺炎的治療，有研究表明烏司他丁可以抑制急性肺損傷/急性呼吸窘迫綜合征的發(fā)生發(fā)展，降低急性肺損傷/急性呼吸窘迫綜合征的病死率，但目前對于烏司他丁的作用機制尚未完全明確，本實驗通過烏司他丁干預膿毒癥性急性肺損傷大鼠HMGB1的表達及水平變化，探討烏司他丁減輕急性肺損傷程度、降低疾病死亡率可能的機制。 第一部分膿毒癥性急性肺損傷大鼠7天生存率觀察 目的通過盲腸結(jié)扎穿刺（CLP）手術法致大鼠膿毒癥性急性肺損傷（ALI），觀察各組大鼠7天生存率，探討烏司他丁有無改善膿毒癥性急性肺損傷大鼠生存率的作用。 方法雄性健康SD大鼠30只隨機分入CLP組，烏司他丁組，假手術組（對照組），每組10只，CLP組大鼠行CLP手術干預，烏司他丁組CLP手術+烏司他丁干預，假手術組僅做腹部開關手術；觀察各組大鼠7天生存率。 結(jié)果CLP組大鼠7天生存率50%，烏司他丁組7天生存率70%，假手術組（對照組）大鼠7天生存率100%，CLP組與烏司他丁組大鼠7天生存率有明顯差異（P＜0.05）。 結(jié)論烏司他丁可以明顯改善膿毒癥性急性肺損傷大鼠7天生存率，早期干預膿毒癥急性肺損傷可能對改善疾病總體預后具有重要作用。 第二部分膿毒癥性急性肺損傷大鼠HMGB1表達及烏司他丁干預的實驗研究 目的通過CLP手術致大鼠膿毒癥性急性肺損傷，烏司他丁干預急性肺損傷，研究烏司他丁對高遷移率族蛋白B1（HMGB1）的表達變化，探討烏司他丁治療膿毒癥性急性肺損傷的分子生物學機制。 方法雄性健康SD大鼠120只隨機分入CLP組、烏司他丁組、假手術組；CLP組、烏司他丁組各40只，，組內(nèi)分6h組10只、12h組10只、24h組10只、48h組10只；假手術組40只,組內(nèi)分組同前。烏司他丁組大鼠于CLP手術30分鐘后按10萬U/kg由大鼠尾靜脈注射烏司他丁，CLP組及假手術組注射等量生理鹽水，各組大鼠在6h、12h、24h、48h設定時間點留取相關標本進行相關指標檢測。 結(jié)果假手術組（對照組）各時點肺組織HMGB1mRNA表達量均顯著低于CLP組、烏司他丁組對應時點肺組織HMGB1mRNA表達量（P0.05）；烏司他丁組HMGB1mRNA表達量在12h、24h、48h點均顯著低于CLP組對應時點（P0.05）；烏司他丁組各時點肺組織中HMGB1含量均顯著低于CLP組中對應時點HMGB1含量（P0.05）。CLP組大鼠血漿中各時點HMGB1含量明顯高于假手術組（對照組）、烏司他丁組對應時點表達含量（P0.05）；烏司他丁組各時點BALF中HMGB1含量均顯著低于CLP組中對應時點HMGB1含量（P0.05）。 結(jié)論HMGB1參與了膿毒癥性急性肺損傷的發(fā)生發(fā)展過程，烏司他丁通過下調(diào)HMGB1的表達達到減輕急性肺損傷程度，提高大鼠生存率的作用。
[Abstract]:Acute lung injury (Acute Lung Injury, ALI) is a syndrome secondary to severe trauma, infection, shock, and major surgery, with respiratory distress and intractable hypoxemia as a clinical feature. Acute lung injury is a prominent manifestation of multiple organ dysfunction syndrome (multiple organ dysfunction syndrome, MODS) in the lungs, and acute respiratory distress syndrome Acute respiratorydistress syndrome (ARDS) is the most serious form of expression. The incidence of acute lung and lung injury is 38/10 million each year. In recent years, there is a tendency to increase gradually. Although many measures have been taken, the mortality of acute lung injury is still as high as 32%-50%, and high mobility group protein B1 (Highmobility group box1protein, HMGB1) is a kind of disease. Advanced inflammatory mediators, also a pro-inflammatory cytokine, can mediate inflammatory reactions and maintain cascade expansion, and their biological characteristics are highly associated with the pathogenesis of various diseases. More and more studies have shown that inflammatory factors play an important role in the development of acute lung injury; Ulinastatin UTI) is a protease inhibitor, early in the treatment of acute pancreatitis. Studies have shown that Ulinastatin can inhibit the development of acute lung injury / acute respiratory distress syndrome and reduce the mortality of acute lung injury / acute respiratory distress syndrome. However, the mechanism of ulinastatin is not yet fully defined. The possible mechanism of Ulinastatin to reduce the degree of acute lung injury and reduce the mortality of the acute lung injury of septic rats was examined through the intervention of ulinastatin in the expression and level of HMGB1 in the rats with acute lung injury.
Part 7 survival rate of septic acute lung injury in rats
Objective To observe the effect of ulinastatin on the survival rate of rats with acute septic lung injury by using the method of cecal ligation (CLP) to induce septic acute lung injury (ALI) in rats, and to observe the 7 natural survival rate of rats in each group.
Methods 30 male healthy SD rats were randomly divided into group CLP, ulinastatin group, sham operation group (control group), 10 in each group. Group CLP rats were treated with CLP operation, ulinastatin group CLP operation plus Ulinastatin, and sham operation group only underwent abdominal switching operation, and the 7 day survival rate of rats in each group was observed.
Results the 7 natural survival rate was 50% in the CLP group, 70% in the Ulinastatin group 7, 100% in the sham operation group (control group) and 100% in the rats in the control group. The survival rate of 7 in the CLP group and the Ulinastatin group was significantly different (P < 0.05).
Conclusion Ulinastatin can significantly improve the 7 born rate of septic acute lung injury in rats. Early intervention in acute lung injury of sepsis may play an important role in improving the overall prognosis of the disease.
The second part is the expression of HMGB1 in septic acute lung injury rats and the intervention of ulinastatin.
Objective to study the effect of ulinastatin on the expression of high mobility group protein B1 (HMGB1) and the molecular mechanism of ulinastatin in the treatment of acute lung injury of sepsis by CLP operation in rats with acute lung injury caused by sepsis.
Methods 120 male healthy SD rats were randomly divided into group CLP, ulinastatin group, sham operation group, CLP group and ulinastatin group 40, group 6h, 10 in group 6h, 10 in group 12h, 10 in group 48h, 40 in group 48h, and 40 in sham operation group, and in group of ulinastatin group at 100 thousand U/kg after 30 minutes of CLP hand, and intravenous injection of ulinastin by 100 thousand U/kg in rat tail veins at 100 thousand U/kg after 100 thousand U/kg The rats in group CLP and sham operation were injected with the same amount of normal saline. The rats in each group were given relevant samples at 6h, 12h, 24h, 48h setting time, and related indexes were detected.
Results the expression of HMGB1mRNA in the lung tissue at all time points in the sham operation group was significantly lower than that in the CLP group. The expression of HMGB1mRNA in the lung tissue at the time point in the Ulinastatin group (P0.05), the HMGB1mRNA expression of the Ulinastatin group in 12h, 24h, 48h were significantly lower than that in the CLP group at the corresponding time point (P0.05), and the HMGB1 content in the lung tissues at each time point in the Ulinastatin group was obvious. The content of HMGB1 in the plasma at the corresponding time point HMGB1 content (P0.05) in group.CLP was significantly higher than that in the sham group (control group) at the corresponding time point of the corresponding time point (P0.05) in group.CLP (P0.05). The content of the BALF in the Ulinastatin group was (P0.05), and the HMGB1 content in the BALF at each time point in the Ulinastatin group was significantly lower than the HMGB1 content at the corresponding time point at the CLP group (P0.05).
Conclusion HMGB1 is involved in the development and development of acute lung injury in sepsis. Ulinastatin can reduce the degree of acute lung injury and improve the survival rate of rats by down regulating the expression of HMGB1.

【學位授予單位】：第二軍醫(yī)大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R459.7

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