肠缺血再灌注肝肺损伤机制及鼠尾草酚保护作用的研究

发布时间：2018-07-28 21:47

【摘要】：肠缺血再灌注(intestinal ischemia reperfusion，IIR)损伤对全身状态的影响已经远远超过肠道局部的损伤和破坏。通常认为，IIR是造成多脏器功能不全综合征(multiple organ dysfunction syndrome，MODS)和全身炎症反应综合征(systemic inflammatory response syndrome，SIRS)的始动因素，是小肠移植的最大障碍，同时肠缺血疾病又有较高的死亡率。肠缺血再灌注引发其它脏器损伤的机制较复杂。过去的研究认为，肠道屏障损害、菌群移位、氧化作用和炎症介质激活经血液直接作用到远隔器官是造成远隔器官损伤的主要原因，但近年研究表明，这种氧化和炎症因子的作用是通过上调核因子κB(nuclear factor kappa B，NFκB)的活化完成的，其是多种信号传导通路的常见终末位点。NFκB是存在于细胞浆中的快速反应性转录因子，，其由分子量为50kDa和65kDa的两个亚单位组成，两者通常与抑制蛋白IκB结合，其可被继发的泛素化(ubiqution)而蛋白水解，被释放的NFκB复合物被转入细胞核，转录激活细胞内黏附因子、白细胞介素及TNF-α等炎症介质基因，造成系统的炎症反应。蛋白酶体(proteasome)是在真核细胞内发现的催化蛋白水解酶的复合物，其在细胞内的蛋白循环中起主要作用。研究表明，泛素-蛋白酶体系统(UPS)对细胞内许多半衰期较短蛋白的选择性降解起重要作用，其参与了对细胞周期调节、基因转录、应激反应或抗原表达调节蛋白的处理及降解。蛋白酶体可能是靶标并
[Abstract]:The effects of intestinal ischemia-reperfusion (intestinal ischemia) injury on the state of the whole body are far greater than those of the intestinal tract. It is generally considered that IIIR is the initiator of multiple organ dysfunction syndrome (multiple organ dysfunction syndromemods) and systemic inflammatory response syndrome (systemic inflammatory response syndrome Sirs). It is the biggest obstacle of small bowel transplantation and has high mortality rate of intestinal ischemia disease. The mechanism of other organ injury induced by intestinal ischemia reperfusion is complicated. Previous studies have shown that intestinal barrier damage, microbial translocation, oxidation and activation of inflammatory mediators directly affect distant organs through blood, but recent studies have shown that The action of this oxidation and inflammatory factor is accomplished by up-regulating the activation of NF 魏 B, which is a common terminal site of many signal transduction pathways. NF 魏 B is a fast reactive transcription factor in cytoplasm. It consists of two subunits with molecular weight of 50kDa and 65kDa. They usually bind to inhibitor I 魏 B, which can be hydrolyzed by secondary ubiquitin (ubiqution). The released NF 魏 B complex is transferred to the nucleus and transcripted to activate the intracellular adhesion factor. Inflammatory mediators, such as interleukin and TNF- 伪, cause systemic inflammation. Proteasome (proteasome) is a complex of catalytic proteolytic enzymes found in eukaryotic cells, which plays a major role in the intracellular protein cycle. It has been shown that the ubiquitin proteasome system (UPS) plays an important role in the selective degradation of many of the short half-life proteins in the cells. It is involved in the treatment and degradation of cell cycle regulation, gene transcription, stress response or antigen expression regulatory proteins. The proteasome may be a target and
【学位授予单位】：大连医科大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R363;R285

【相似文献】