HMGB1在MODS小鼠脾臟中的表達(dá)及意義的研究
發(fā)布時(shí)間：2019-01-21 10:48
【摘要】：目前認(rèn)為,多器官功能障礙綜合征(multiple organs dysfunction syndrome, MODS)的發(fā)病基礎(chǔ)是失控性全身炎癥反應(yīng)。最近的研究發(fā)現(xiàn),高遷移率族蛋白-1(high mobility group box-1 protein, HMGB1)是膿毒癥及脂多糖誘導(dǎo)的致死性全身炎癥反應(yīng)的晚期介導(dǎo)因子,HMGB1有望成為臨床MODS治療的一個(gè)新的有效的干預(yù)靶點(diǎn)。為了明確HMGB1是否可參與不同原因引起的MODS發(fā)病過程、了解MODS病程中HMGB1表達(dá)和釋放規(guī)律、了解MODS病程中免疫器官與HMGB1釋放的關(guān)系及HMGB1與免疫功能狀態(tài)的關(guān)系,我們制作了酵母多糖致小鼠MODS模型,檢測(cè)了病程中血清HMGB1的變化情況,同時(shí)觀察脾臟HMGB1表達(dá)情況及脾臟病理、部分免疫相關(guān)指標(biāo)和脾臟樹突狀細(xì)胞(dendritic cells, DCs)功能狀態(tài)的變化情況,并分析以上變化的時(shí)相關(guān)系,進(jìn)而推測(cè)HMGB1在酵母多糖致小鼠MODS發(fā)病中的作用、脾臟HMGB1表達(dá)的功能意義及HMGB1與免疫功能的關(guān)系。 實(shí)驗(yàn)結(jié)果發(fā)現(xiàn):在正常組和病程早期(3-8小時(shí)),HMGB1在血清中幾乎檢測(cè)不到,病情進(jìn)入急性損傷期(12-48小時(shí))時(shí)血清中HMGB1開始升高,很快達(dá)到高峰并維持至急性損傷期結(jié)束,緩解期(5天)又降至正常水平,臟器衰竭期(10-12天)時(shí)再次顯著升高;脾臟HMGB1表達(dá)在致傷后3小時(shí)即開始升高并在8小時(shí)形成一個(gè)小高峰,而在急性損傷期早期表達(dá)水平下降,之后再次升高并在2天時(shí)達(dá)高峰,其水平遠(yuǎn)高于第一個(gè)高峰,緩解期表達(dá)水平下降至接近正常水平,而臟器衰竭期又有升高,但低于2天時(shí)水平。同時(shí),免疫組化顯示HMGB1的亞細(xì)胞定位有一個(gè)由胞核到胞漿直至細(xì)胞間質(zhì)的變化過程;致傷早期脾臟免疫細(xì)胞增殖活躍,但急性損傷期脾臟可見大量淋巴細(xì)胞凋亡和中性粒細(xì)胞浸潤(rùn),緩解期凋亡細(xì)胞減少,臟器衰竭期脾臟免疫細(xì)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.
【學(xué)位授予單位】：中國(guó)人民解放軍軍事醫(yī)學(xué)科學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2005
【分類號(hào)】：R363
本文編號(hào)：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.
【學(xué)位授予單位】：中國(guó)人民解放軍軍事醫(yī)學(xué)科學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2005
【分類號(hào)】：R363
【參考文獻(xiàn)】
中國(guó)期刊全文數(shù)據(jù)庫(kù) 前3條
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2 孫宇,陸江陽(yáng),王曉虹,胡森,楊毅,佟欣;小鼠遲發(fā)型多器官功能障礙綜合征模型復(fù)制及病理學(xué)觀察[J];中國(guó)危重病急救醫(yī)學(xué);2003年01期
3 黃文華;創(chuàng)傷后免疫功能紊亂與感染并發(fā)癥[J];中國(guó)危重病急救醫(yī)學(xué);1998年12期
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