调控凝血活性对老年大鼠炎症反应影响的机制研究

发布时间：2018-01-13 21:17

本文关键词：调控凝血活性对老年大鼠炎症反应影响的机制研究　出处：《中国人民解放军军医进修学院》2006年博士论文　论文类型：学位论文

【摘要】：背景凝血异常和纤维蛋白沉积见于人类许多类型的炎症反应,并且与炎症损害密切相关,基础研究表明,凝血系统参与炎症调节。临床资料和我们的前期研究发现,老年机体存在高凝状态,同时老年个体较青年个体对各种炎症刺激和病理损伤更加易感,因此我们推测老年个体的高凝状态促进了炎症反应。但老年个体高凝状态的原因及其对老年个体炎症反应影响的机制目前尚不十分清楚。目的为验证我们的假说,本研究首先观察生理与炎症状态下老年大鼠肺组织和肾脏局部凝血活性的改变,探讨老年机体高凝状态形成的机制;其次,观察调控凝血活性对炎症的影响,从整体水平探讨高凝状态促进老年大鼠炎症反应的机制;最后从细胞水平阐明凝血系统调节炎症反应的分子机制。方法雌性Wistar 3月龄(青年鼠)和27月龄(老年鼠)大鼠均随机分为正常对照组(NC组)、脂多糖组(L组)、脂多糖+氨甲环酸组(LT组)、脂多糖+氨甲环酸+肝素组(LTH组)、脂多糖+氨甲环酸+尿激酶组(LTU组)以及氨甲环酸组(T组)。以LPS腹腔注射诱导大鼠急性炎症,并用氨甲环酸(TA)和肝素/或尿激酶(UK)调控凝血活性。分别采用免疫组化、Western Blot与Northern Blot检测各指标蛋白质与基因表达。比较同一鼠龄组内各处理组间以及相同处理的两鼠龄组间纤溶酶原活化抑制物1(PAI-1)、血栓调节蛋白(TM)、凝血酶受体(TR)蛋白质与mRNA表达水平和纤维蛋白沉积水平;以及浸润的炎细胞数目、单核细胞趋化蛋白1(MCP-1)、细胞间粘附分子1(ICAM-1)蛋白质和mRNA的表达。并在体外实验比较纤维蛋白和TR途径对内皮细胞ICAM-1表达和黏附单核细胞能力的影响。结果 (1)青年鼠和老年鼠NC组的肺组织和肾组织均无PAI-1表达,而TM表达丰富;L组青年鼠和老年鼠肺组织和肾组织PAI-1的蛋白质与mRNA表达水平均上调,老年鼠上调幅度明显高于青年鼠(P0.05),而青年鼠和老年鼠几乎无TM表达。(2)青年鼠和老年鼠NC组的肺组织和肾组织均无纤维蛋白沉积,有少量TR表达;两鼠龄的L组纤维蛋白
[Abstract]:Background abnormal coagulation and fibrin deposition are found in many types of inflammatory reactions in humans and are closely related to inflammatory damage. Coagulation system is involved in inflammation regulation. Clinical data and our previous studies found that the elderly have hypercoagulable state, and elderly individuals are more susceptible to various inflammatory stimuli and pathological damage than young individuals. Therefore, we speculate that hypercoagulability promotes inflammation in elderly individuals, but the causes of hypercoagulability and the mechanism of its influence on inflammation in elderly individuals are still unclear. To test our hypothesis. In this study, we first observed the changes of local coagulation activity in lung tissue and kidney of aged rats under physiological and inflammatory conditions, and explored the mechanism of hypercoagulability in aged rats. Secondly, the effect of regulating coagulation activity on inflammation was observed, and the mechanism of hypercoagulability promoting inflammation in aged rats was discussed from the whole level. Finally, the molecular mechanism of coagulation system regulating inflammatory response was elucidated at the cellular level. Methods female Wistar 3-month-old (young) and 27-month-old (aged) rats were randomly divided into normal control group (P < 0.05). NC group). Lipopolysaccharide group (L group), lipopolysaccharide formic acid group (LT group), lipopolysaccharide carbamate heparin group (LTH group). The acute inflammation was induced by intraperitoneal injection of LPS. The coagulation activity was regulated by TAA and UK. Immunohistochemistry was used respectively. Western Blot and Northern. Blot was used to detect the expression of protein and gene. Plasminogen activator inhibitor 1 (plasminogen activator inhibitor 1) was compared between different treatment groups within the same age group and two groups with the same treatment. PAI-1). Thrombomodulin (TMN), thrombin receptor (TRT) protein and mRNA expression level and fibrin deposition level; And the number of infiltrating inflammatory cells, monocyte chemoattractant protein (MCP-1). Intercellular adhesion molecule 1 (ICAM-1). Expression of protein and mRNA. Effects of fibrin and tr pathway on ICAM-1 expression and monocyte adhesion in endothelial cells were compared in vitro. There was no PAI-1 expression in lung and kidney tissues of young rats and old rats in NC group. The expression of TM was abundant. In group L, the expression of PAI-1 protein and mRNA was up-regulated in lung and kidney tissues of young and aged rats, and the up-regulation of mRNA in aged rats was significantly higher than that in young rats (P0.05). However, there was almost no TM expression in young rats and aged rats. (2) there was no fibrin deposition in lung and kidney tissues of young rats and old rats in NC group, but a small amount of tr expression. L-Group Fibrin of two Rat Ages
【学位授予单位】：中国人民解放军军医进修学院
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R363

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