發(fā)布時間：2018-04-28 11:46

  本文選題：膿毒癥 + 烏司他丁　； 參考：《福建醫(yī)科大學(xué)》2016年碩士論文

【摘要】：膿毒癥是感染引起的全身炎癥反應(yīng)綜合征(SIRS)。心功能障礙常出現(xiàn)在嚴重膿毒癥和膿毒癥休克中,但其發(fā)生發(fā)展的機制尚未完全明了。其中心肌能量代謝障礙是心肌細胞損傷的始動環(huán)節(jié)之一,是引起和促進心功能障礙發(fā)生、發(fā)展的重要因素。針對膿毒癥和膿毒癥休克的診療方法一直在不斷地尋找改良和運用,除了經(jīng)典抗感染治療、液體復(fù)蘇、保護性通氣等,一些輔助治療也越來越多的被關(guān)注、被研究與應(yīng)用,包括糖皮質(zhì)激素的應(yīng)用、免疫球蛋白的使用、抗凝劑的應(yīng)用、血糖控制、他汀類藥物的應(yīng)用,以及烏司他丁的使用等。烏司他丁(UTI)是從人尿中提取的精制的蛋白酶抑制劑,可抑制胰蛋白酶、彈性蛋白酶、纖溶酶等蛋白水解酶以及透明質(zhì)酸酶、淀粉酶、脂肪酶等糖類和脂類水解酶。目前國內(nèi)外關(guān)于烏司他丁對膿毒癥心肌能量代謝的研究較少,特別是幾乎無相關(guān)的基因水平上的研究。本實驗將在基因水平上探究烏司他丁對膿毒癥心肌能量代謝的影響及推斷其可能的作用機制,為臨床上合理用藥提供依據(jù)。方法:45只雄性Wistar大鼠隨機分為對照組、膿毒癥組和烏司他丁組。采用盲腸結(jié)扎穿孔術(shù)(CLP)制作膿毒癥大鼠模型;對照組僅開腹、關(guān)腹,不行CLP。烏司他丁組于制模前1 h肌肉注射烏司他丁10萬u/kg;術(shù)后每隔8個小時重復(fù)給藥,膿毒癥組及假手術(shù)組肌注平衡液5 ml/kg。于CLP術(shù)后24 h在氯胺酮腹腔麻醉下迅速開腹、取心臟,并立即置入液氮中,-70℃保存,以待提取RNA。運用RT2profile PCR陣列技術(shù)進行檢測,分析比較膿毒癥組、烏司他丁組與對照組大鼠心肌能量代謝相關(guān)基因表達的變化,并比較分析膿毒癥組和烏司他丁組差異表達基因之間的不同。結(jié)果:膿毒癥組和烏司他丁組均出現(xiàn)了心肌能量代謝相關(guān)基因表達變化。與對照組相比,烏司他丁組中有11個基因出現(xiàn)差異表達,其中有9個表達下調(diào)(Atp12a、Atp4a、Atp5d、Atp6v0a2、Atp6v1g3、Cox4i2、Cyc1、Slc25a10、Slc25a15、),2個表達上調(diào)(Atp6v0d2、Atp6v1e2);膿毒癥組有5個基因出現(xiàn)差異表達,其中有2個表達下調(diào)(Atp6v1g3、Ucp1),3個表達上調(diào)(Atp12a、Atp4a、Ucp3)。烏司他丁組和膿毒癥組表達差異的基因有所不同,烏司他丁有調(diào)節(jié)作用的基因有13個。涉及的基因編碼的蛋白主要與呼吸鏈酶復(fù)合物V(ATP合酶)、酶復(fù)合體IV(細胞色素c氧化酶)、酶復(fù)合體III(輔酶Q-細胞色素c還原酶)和能量代謝相關(guān)的輔助蛋白有關(guān)。結(jié)論:膿毒癥時機體出現(xiàn)了心肌能量代謝方面的改變,烏司他丁對膿毒癥誘發(fā)的心肌能量代謝障礙起到一定改善作用。
[Abstract]:Sepsis is a systemic inflammatory response syndrome caused by infection. Cardiac dysfunction often occurs in severe sepsis and septic shock, but the mechanism of its development has not been fully understood. Among them, myocardial energy metabolism disorder is one of the initiation links of myocardial cell injury, which is an important factor to cause and promote the occurrence and development of cardiac dysfunction. The methods of diagnosis and treatment for sepsis and septic shock have been constantly looking for improvement and application. In addition to classical antiinfective therapy, fluid resuscitation, protective ventilation, and so on, some adjuvant treatments have been paid more and more attention to, studied and applied. These include the use of glucocorticoids, immunoglobulin, anticoagulants, blood glucose control, statins, and ulinastatin. Ulinastatin UTI is a refined protease inhibitor extracted from human urine. It can inhibit proteolytic enzymes such as trypsin, elastase, fibrinolytic enzyme, hyaluronidase, amylase, lipase and so on. There are few studies on the energy metabolism of sepsis myocardium at home and abroad, especially at the level of almost no related genes. This study will explore the effect of ulinastatin on myocardial energy metabolism in sepsis and its possible mechanism at the gene level. Methods 45 male Wistar rats were randomly divided into control group, septic group and ulinastatin group. The sepsis rat model was made by cecal ligation and perforation, while the control group was only open and closed abdomen, but not CLP. Ulinastatin group was intramuscularly injected with ulinastatin 100000 u / kg one hour before model making, and repeated administration every 8 hours after operation. The sepsis group and sham operation group were injected intramuscularly with a balanced solution of 5 ml / kg. After 24 hours after CLP, the heart was quickly opened under ketamine abdominal anesthesia, and the heart was stored in liquid nitrogen at -70 鈩，

本文編號：1815150