HMGB1在MODS小鼠脾脏中的表达及意义的研究
发布时间：2019-01-21 10:48
【摘要】：目前认为,多器官功能障碍综合征(multiple organs dysfunction syndrome, MODS)的发病基础是失控性全身炎症反应。最近的研究发现,高迁移率族蛋白-1(high mobility group box-1 protein, HMGB1)是脓毒症及脂多糖诱导的致死性全身炎症反应的晚期介导因子,HMGB1有望成为临床MODS治疗的一个新的有效的干预靶点。为了明确HMGB1是否可参与不同原因引起的MODS发病过程、了解MODS病程中HMGB1表达和释放规律、了解MODS病程中免疫器官与HMGB1释放的关系及HMGB1与免疫功能状态的关系,我们制作了酵母多糖致小鼠MODS模型,检测了病程中血清HMGB1的变化情况,同时观察脾脏HMGB1表达情况及脾脏病理、部分免疫相关指标和脾脏树突状细胞(dendritic cells, DCs)功能状态的变化情况,并分析以上变化的时相关系,进而推测HMGB1在酵母多糖致小鼠MODS发病中的作用、脾脏HMGB1表达的功能意义及HMGB1与免疫功能的关系。 实验结果发现:在正常组和病程早期(3-8小时),HMGB1在血清中几乎检测不到,病情进入急性损伤期(12-48小时)时血清中HMGB1开始升高,很快达到高峰并维持至急性损伤期结束,缓解期(5天)又降至正常水平,脏器衰竭期(10-12天)时再次显著升高;脾脏HMGB1表达在致伤后3小时即开始升高并在8小时形成一个小高峰,而在急性损伤期早期表达水平下降,之后再次升高并在2天时达高峰,其水平远高于第一个高峰,缓解期表达水平下降至接近正常水平,而脏器衰竭期又有升高,但低于2天时水平。同时,免疫组化显示HMGB1的亚细胞定位有一个由胞核到胞浆直至细胞间质的变化过程;致伤早期脾脏免疫细胞增殖活跃,但急性损伤期脾脏可见大量淋巴细胞凋亡和中性粒细胞浸润,缓解期凋亡细胞减少,脏器衰竭期脾脏免疫细胞多呈溶
[Abstract]:At present, the pathogenesis of multiple organ dysfunction syndrome (multiple organs dysfunction syndrome, MODS) is based on uncontrolled systemic inflammation. Recent studies have found that high mobility protein-1 (high mobility group box-1 protein, HMGB1) is a late mediator of sepsis and lipopolysaccharide-induced fatal systemic inflammation. HMGB1 is expected to be a new and effective intervention target for clinical MODS therapy. In order to know whether HMGB1 can participate in the pathogenesis of MODS caused by different causes, to understand the expression and release of HMGB1 in the course of MODS, the relationship between immune organs and HMGB1 release in the course of MODS, and the relationship between HMGB1 and immune function state. The MODS model of mice induced by yeast polysaccharides was made, and the changes of serum HMGB1 in the course of disease were detected. Meanwhile, the expression of HMGB1 in spleen, the pathological changes of spleen, some immunological indexes and (dendritic cells, of spleen dendritic cells were observed. The changes of DCs) function state were analyzed, and the time-phase relationship of the above changes was analyzed, and the role of HMGB1 in the pathogenesis of MODS induced by yeast polysaccharides, the functional significance of HMGB1 expression in spleen and the relationship between HMGB1 and immune function in mice were speculated. The results showed that in the normal group and in the early stage of the disease (3-8 hours), HMGB1 was almost undetectable in serum, and HMGB1 began to increase at the time of acute injury (12-48 hours). The peak was quickly reached and maintained until the end of the acute injury period, the remission period (5 days) decreased to normal level, and the organ failure period (10-12 days) increased significantly again. The expression of HMGB1 in spleen began to increase at 3 hours after injury and reached a small peak at 8 hours, but decreased in the early stage of acute injury, then increased again and reached its peak at 2 days, which was much higher than the first peak. The expression level decreased to the normal level in the remission stage, but increased in the organ failure stage, but it was lower than the level at 2 days. At the same time, immunohistochemistry showed that the subcellular localization of HMGB1 was a process from nucleus to cytoplasm to interstitial. Splenic immune cells proliferate actively in the early stage of injury, but a large number of lymphocytes apoptosis and neutrophil infiltration can be seen in the spleen during acute injury, apoptotic cells decrease in the remission phase, and spleen immune cells dissolve in the stage of organ failure.
【学位授予单位】：中国人民解放军军事医学科学院
【学位级别】：硕士
【学位授予年份】：2005
【分类号】：R363
本文编号：2412586
[Abstract]:At present, the pathogenesis of multiple organ dysfunction syndrome (multiple organs dysfunction syndrome, MODS) is based on uncontrolled systemic inflammation. Recent studies have found that high mobility protein-1 (high mobility group box-1 protein, HMGB1) is a late mediator of sepsis and lipopolysaccharide-induced fatal systemic inflammation. HMGB1 is expected to be a new and effective intervention target for clinical MODS therapy. In order to know whether HMGB1 can participate in the pathogenesis of MODS caused by different causes, to understand the expression and release of HMGB1 in the course of MODS, the relationship between immune organs and HMGB1 release in the course of MODS, and the relationship between HMGB1 and immune function state. The MODS model of mice induced by yeast polysaccharides was made, and the changes of serum HMGB1 in the course of disease were detected. Meanwhile, the expression of HMGB1 in spleen, the pathological changes of spleen, some immunological indexes and (dendritic cells, of spleen dendritic cells were observed. The changes of DCs) function state were analyzed, and the time-phase relationship of the above changes was analyzed, and the role of HMGB1 in the pathogenesis of MODS induced by yeast polysaccharides, the functional significance of HMGB1 expression in spleen and the relationship between HMGB1 and immune function in mice were speculated. The results showed that in the normal group and in the early stage of the disease (3-8 hours), HMGB1 was almost undetectable in serum, and HMGB1 began to increase at the time of acute injury (12-48 hours). The peak was quickly reached and maintained until the end of the acute injury period, the remission period (5 days) decreased to normal level, and the organ failure period (10-12 days) increased significantly again. The expression of HMGB1 in spleen began to increase at 3 hours after injury and reached a small peak at 8 hours, but decreased in the early stage of acute injury, then increased again and reached its peak at 2 days, which was much higher than the first peak. The expression level decreased to the normal level in the remission stage, but increased in the organ failure stage, but it was lower than the level at 2 days. At the same time, immunohistochemistry showed that the subcellular localization of HMGB1 was a process from nucleus to cytoplasm to interstitial. Splenic immune cells proliferate actively in the early stage of injury, but a large number of lymphocytes apoptosis and neutrophil infiltration can be seen in the spleen during acute injury, apoptotic cells decrease in the remission phase, and spleen immune cells dissolve in the stage of organ failure.
【学位授予单位】：中国人民解放军军事医学科学院
【学位级别】：硕士
【学位授予年份】：2005
【分类号】：R363
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