Endothelial progenitor cells modulated by IL-1β in multiple organ dysfunction syndrome in porcine

Objective To investigate the modulation of EPCs by interleukin 1β (IL-1β) and p38 mitogen activated protein kinase (p38MAPK) and the pathogenesis resulting from their dysdifferenfiation after trauma.Method Thirty pigs were divided into a control group (n = 15) and a multiple organ dysfimction syndrome (MODS) group (n = 15), the latter of which were subjected to a "two-hit" injury including hemon'hagic shock and endotoxemia. Phosphorylation of p38MAPK in peripheral blood mononuclear cells was monitored by western blotting. The concentration of IL-1β in peripheral blood plasma was determined by ELISA and the numbers of EPCs with FCM in peripheral blood plasma were monitored. The morbidity rates in the two groups were compared by chi square test. The levels of phosphorylation of p38MAPK in peripheral blood mononuclear cells, the concentmtions of IL-1β in peripheral blood plasma and the numbers of EPCs in the peripheral blood were compared between groups using with Student's t lest. Results The level of p38MAPK phosphorylation was more augmented and the concen-tration of IL-1β higher in peripheral blood mononuelear cells and plasma from MODS pigs compared with those from control pigs; nevertheless the mauler of EPC conspicuously decreased in the peripheral blood (P <0.01). The morbidity rate in the MODS group was much higher than that in the control group (P < 0.01). There were fewer EPCs in the peripheral blood of animals in group M than in the peripheral blood of animals in group C (P <0.01). Conclusions p38MAPK phosphorylation is important for the pathogenesis of MODS. p38MAPK phospho-rylation might cause the concentration of IL-1β in the peripheral blood plasma to rise and could cause a drop in the numbers of EPCs, thereby aggravating the inflanmmatory reaction in MODS.     

Endothelial progenitor cells modulated by IL-1β in multiple organ dysfunction syndrome in porcine

Objective To investigate the modulation of EPCs by interleukin 1β (IL-1β) and p38 mitogen activated protein kinase (p38MAPK) and the pathogenesis resulting from their dysdifferenfiation after trauma.Method Thirty pigs were divided into a control group (n = 15) and a multiple organ dysfimction syndrome (MODS) group (n = 15), the latter of which were subjected to a "two-hit" injury including hemon'hagic shock and endotoxemia. Phosphorylation of p38MAPK in peripheral blood mononuclear cells was monitored by western blotting. The concentration of IL-1β in peripheral blood plasma was determined by ELISA and the numbers of EPCs with FCM in peripheral blood plasma were monitored. The morbidity rates in the two groups were compared by chi square test. The levels of phosphorylation of p38MAPK in peripheral blood mononuclear cells, the concentmtions of IL-1β in peripheral blood plasma and the numbers of EPCs in the peripheral blood were compared between groups using with Student's t lest. Results The level of p38MAPK phosphorylation was more augmented and the concen-tration of IL-1β higher in peripheral blood mononuelear cells and plasma from MODS pigs compared with those from control pigs; nevertheless the mauler of EPC conspicuously decreased in the peripheral blood (P <0.01). The morbidity rate in the MODS group was much higher than that in the control group (P < 0.01). There were fewer EPCs in the peripheral blood of animals in group M than in the peripheral blood of animals in group C (P <0.01). Conclusions p38MAPK phosphorylation is important for the pathogenesis of MODS. p38MAPK phospho-rylation might cause the concentration of IL-1β in the peripheral blood plasma to rise and could cause a drop in the numbers of EPCs, thereby aggravating the inflanmmatory reaction in MODS.     

Endothelial progenitor cells modulated by IL-1β in multiple organ dysfunction syndrome in porcine

Objective To investigate the modulation of EPCs by interleukin 1β (IL-1β) and p38 mitogen activated protein kinase (p38MAPK) and the pathogenesis resulting from their dysdifferenfiation after trauma.Method Thirty pigs were divided into a control group (n = 15) and a multiple organ dysfimction syndrome (MODS) group (n = 15), the latter of which were subjected to a "two-hit" injury including hemon'hagic shock and endotoxemia. Phosphorylation of p38MAPK in peripheral blood mononuclear cells was monitored by western blotting. The concentration of IL-1β in peripheral blood plasma was determined by ELISA and the numbers of EPCs with FCM in peripheral blood plasma were monitored. The morbidity rates in the two groups were compared by chi square test. The levels of phosphorylation of p38MAPK in peripheral blood mononuclear cells, the concentmtions of IL-1β in peripheral blood plasma and the numbers of EPCs in the peripheral blood were compared between groups using with Student's t lest. Results The level of p38MAPK phosphorylation was more augmented and the concen-tration of IL-1β higher in peripheral blood mononuelear cells and plasma from MODS pigs compared with those from control pigs; nevertheless the mauler of EPC conspicuously decreased in the peripheral blood (P <0.01). The morbidity rate in the MODS group was much higher than that in the control group (P < 0.01). There were fewer EPCs in the peripheral blood of animals in group M than in the peripheral blood of animals in group C (P <0.01). Conclusions p38MAPK phosphorylation is important for the pathogenesis of MODS. p38MAPK phospho-rylation might cause the concentration of IL-1β in the peripheral blood plasma to rise and could cause a drop in the numbers of EPCs, thereby aggravating the inflanmmatory reaction in MODS.     

Endothelial progenitor cells modulated by IL-1β in multiple organ dysfunction syndrome in porcine

Objective To investigate the modulation of EPCs by interleukin 1β (IL-1β) and p38 mitogen activated protein kinase (p38MAPK) and the pathogenesis resulting from their dysdifferenfiation after trauma.Method Thirty pigs were divided into a control group (n = 15) and a multiple organ dysfimction syndrome (MODS) group (n = 15), the latter of which were subjected to a "two-hit" injury including hemon'hagic shock and endotoxemia. Phosphorylation of p38MAPK in peripheral blood mononuclear cells was monitored by western blotting. The concentration of IL-1β in peripheral blood plasma was determined by ELISA and the numbers of EPCs with FCM in peripheral blood plasma were monitored. The morbidity rates in the two groups were compared by chi square test. The levels of phosphorylation of p38MAPK in peripheral blood mononuclear cells, the concentmtions of IL-1β in peripheral blood plasma and the numbers of EPCs in the peripheral blood were compared between groups using with Student's t lest. Results The level of p38MAPK phosphorylation was more augmented and the concen-tration of IL-1β higher in peripheral blood mononuelear cells and plasma from MODS pigs compared with those from control pigs; nevertheless the mauler of EPC conspicuously decreased in the peripheral blood (P <0.01). The morbidity rate in the MODS group was much higher than that in the control group (P < 0.01). There were fewer EPCs in the peripheral blood of animals in group M than in the peripheral blood of animals in group C (P <0.01). Conclusions p38MAPK phosphorylation is important for the pathogenesis of MODS. p38MAPK phospho-rylation might cause the concentration of IL-1β in the peripheral blood plasma to rise and could cause a drop in the numbers of EPCs, thereby aggravating the inflanmmatory reaction in MODS.     

Endothelial progenitor cells modulated by IL-1β in multiple organ dysfunction syndrome in porcine

Objective To investigate the modulation of EPCs by interleukin 1β (IL-1β) and p38 mitogen activated protein kinase (p38MAPK) and the pathogenesis resulting from their dysdifferenfiation after trauma.Method Thirty pigs were divided into a control group (n = 15) and a multiple organ dysfimction syndrome (MODS) group (n = 15), the latter of which were subjected to a "two-hit" injury including hemon'hagic shock and endotoxemia. Phosphorylation of p38MAPK in peripheral blood mononuclear cells was monitored by western blotting. The concentration of IL-1β in peripheral blood plasma was determined by ELISA and the numbers of EPCs with FCM in peripheral blood plasma were monitored. The morbidity rates in the two groups were compared by chi square test. The levels of phosphorylation of p38MAPK in peripheral blood mononuclear cells, the concentmtions of IL-1β in peripheral blood plasma and the numbers of EPCs in the peripheral blood were compared between groups using with Student's t lest. Results The level of p38MAPK phosphorylation was more augmented and the concen-tration of IL-1β higher in peripheral blood mononuelear cells and plasma from MODS pigs compared with those from control pigs; nevertheless the mauler of EPC conspicuously decreased in the peripheral blood (P <0.01). The morbidity rate in the MODS group was much higher than that in the control group (P < 0.01). There were fewer EPCs in the peripheral blood of animals in group M than in the peripheral blood of animals in group C (P <0.01). Conclusions p38MAPK phosphorylation is important for the pathogenesis of MODS. p38MAPK phospho-rylation might cause the concentration of IL-1β in the peripheral blood plasma to rise and could cause a drop in the numbers of EPCs, thereby aggravating the inflanmmatory reaction in MODS.     

Endothelial progenitor cells modulated by IL-1β in multiple organ dysfunction syndrome in porcine

Objective To investigate the modulation of EPCs by interleukin 1β (IL-1β) and p38 mitogen activated protein kinase (p38MAPK) and the pathogenesis resulting from their dysdifferenfiation after trauma.Method Thirty pigs were divided into a control group (n = 15) and a multiple organ dysfimction syndrome (MODS) group (n = 15), the latter of which were subjected to a "two-hit" injury including hemon'hagic shock and endotoxemia. Phosphorylation of p38MAPK in peripheral blood mononuclear cells was monitored by western blotting. The concentration of IL-1β in peripheral blood plasma was determined by ELISA and the numbers of EPCs with FCM in peripheral blood plasma were monitored. The morbidity rates in the two groups were compared by chi square test. The levels of phosphorylation of p38MAPK in peripheral blood mononuclear cells, the concentmtions of IL-1β in peripheral blood plasma and the numbers of EPCs in the peripheral blood were compared between groups using with Student's t lest. Results The level of p38MAPK phosphorylation was more augmented and the concen-tration of IL-1β higher in peripheral blood mononuelear cells and plasma from MODS pigs compared with those from control pigs; nevertheless the mauler of EPC conspicuously decreased in the peripheral blood (P <0.01). The morbidity rate in the MODS group was much higher than that in the control group (P < 0.01). There were fewer EPCs in the peripheral blood of animals in group M than in the peripheral blood of animals in group C (P <0.01). Conclusions p38MAPK phosphorylation is important for the pathogenesis of MODS. p38MAPK phospho-rylation might cause the concentration of IL-1β in the peripheral blood plasma to rise and could cause a drop in the numbers of EPCs, thereby aggravating the inflanmmatory reaction in MODS.     

Endothelial progenitor cells modulated by IL-1β in multiple organ dysfunction syndrome in porcine

Objective To investigate the modulation of EPCs by interleukin 1β (IL-1β) and p38 mitogen activated protein kinase (p38MAPK) and the pathogenesis resulting from their dysdifferenfiation after trauma.Method Thirty pigs were divided into a control group (n = 15) and a multiple organ dysfimction syndrome (MODS) group (n = 15), the latter of which were subjected to a "two-hit" injury including hemon'hagic shock and endotoxemia. Phosphorylation of p38MAPK in peripheral blood mononuclear cells was monitored by western blotting. The concentration of IL-1β in peripheral blood plasma was determined by ELISA and the numbers of EPCs with FCM in peripheral blood plasma were monitored. The morbidity rates in the two groups were compared by chi square test. The levels of phosphorylation of p38MAPK in peripheral blood mononuclear cells, the concentmtions of IL-1β in peripheral blood plasma and the numbers of EPCs in the peripheral blood were compared between groups using with Student's t lest. Results The level of p38MAPK phosphorylation was more augmented and the concen-tration of IL-1β higher in peripheral blood mononuelear cells and plasma from MODS pigs compared with those from control pigs; nevertheless the mauler of EPC conspicuously decreased in the peripheral blood (P <0.01). The morbidity rate in the MODS group was much higher than that in the control group (P < 0.01). There were fewer EPCs in the peripheral blood of animals in group M than in the peripheral blood of animals in group C (P <0.01). Conclusions p38MAPK phosphorylation is important for the pathogenesis of MODS. p38MAPK phospho-rylation might cause the concentration of IL-1β in the peripheral blood plasma to rise and could cause a drop in the numbers of EPCs, thereby aggravating the inflanmmatory reaction in MODS.     

Endothelial progenitor cells modulated by IL-1β in multiple organ dysfunction syndrome in porcine

Objective To investigate the modulation of EPCs by interleukin 1β (IL-1β) and p38 mitogen activated protein kinase (p38MAPK) and the pathogenesis resulting from their dysdifferenfiation after trauma.Method Thirty pigs were divided into a control group (n = 15) and a multiple organ dysfimction syndrome (MODS) group (n = 15), the latter of which were subjected to a "two-hit" injury including hemon'hagic shock and endotoxemia. Phosphorylation of p38MAPK in peripheral blood mononuclear cells was monitored by western blotting. The concentration of IL-1β in peripheral blood plasma was determined by ELISA and the numbers of EPCs with FCM in peripheral blood plasma were monitored. The morbidity rates in the two groups were compared by chi square test. The levels of phosphorylation of p38MAPK in peripheral blood mononuclear cells, the concentmtions of IL-1β in peripheral blood plasma and the numbers of EPCs in the peripheral blood were compared between groups using with Student's t lest. Results The level of p38MAPK phosphorylation was more augmented and the concen-tration of IL-1β higher in peripheral blood mononuelear cells and plasma from MODS pigs compared with those from control pigs; nevertheless the mauler of EPC conspicuously decreased in the peripheral blood (P <0.01). The morbidity rate in the MODS group was much higher than that in the control group (P < 0.01). There were fewer EPCs in the peripheral blood of animals in group M than in the peripheral blood of animals in group C (P <0.01). Conclusions p38MAPK phosphorylation is important for the pathogenesis of MODS. p38MAPK phospho-rylation might cause the concentration of IL-1β in the peripheral blood plasma to rise and could cause a drop in the numbers of EPCs, thereby aggravating the inflanmmatory reaction in MODS.     

Endothelial progenitor cells modulated by IL-1β in multiple organ dysfunction syndrome in porcine

Objective To investigate the modulation of EPCs by interleukin 1β (IL-1β) and p38 mitogen activated protein kinase (p38MAPK) and the pathogenesis resulting from their dysdifferenfiation after trauma.Method Thirty pigs were divided into a control group (n = 15) and a multiple organ dysfimction syndrome (MODS) group (n = 15), the latter of which were subjected to a "two-hit" injury including hemon'hagic shock and endotoxemia. Phosphorylation of p38MAPK in peripheral blood mononuclear cells was monitored by western blotting. The concentration of IL-1β in peripheral blood plasma was determined by ELISA and the numbers of EPCs with FCM in peripheral blood plasma were monitored. The morbidity rates in the two groups were compared by chi square test. The levels of phosphorylation of p38MAPK in peripheral blood mononuclear cells, the concentmtions of IL-1β in peripheral blood plasma and the numbers of EPCs in the peripheral blood were compared between groups using with Student's t lest. Results The level of p38MAPK phosphorylation was more augmented and the concen-tration of IL-1β higher in peripheral blood mononuelear cells and plasma from MODS pigs compared with those from control pigs; nevertheless the mauler of EPC conspicuously decreased in the peripheral blood (P <0.01). The morbidity rate in the MODS group was much higher than that in the control group (P < 0.01). There were fewer EPCs in the peripheral blood of animals in group M than in the peripheral blood of animals in group C (P <0.01). Conclusions p38MAPK phosphorylation is important for the pathogenesis of MODS. p38MAPK phospho-rylation might cause the concentration of IL-1β in the peripheral blood plasma to rise and could cause a drop in the numbers of EPCs, thereby aggravating the inflanmmatory reaction in MODS.     

Endothelial progenitor cells modulated by IL-1β in multiple organ dysfunction syndrome in porcine

Objective To investigate the modulation of EPCs by interleukin 1β (IL-1β) and p38 mitogen activated protein kinase (p38MAPK) and the pathogenesis resulting from their dysdifferenfiation after trauma.Method Thirty pigs were divided into a control group (n = 15) and a multiple organ dysfimction syndrome (MODS) group (n = 15), the latter of which were subjected to a "two-hit" injury including hemon'hagic shock and endotoxemia. Phosphorylation of p38MAPK in peripheral blood mononuclear cells was monitored by western blotting. The concentration of IL-1β in peripheral blood plasma was determined by ELISA and the numbers of EPCs with FCM in peripheral blood plasma were monitored. The morbidity rates in the two groups were compared by chi square test. The levels of phosphorylation of p38MAPK in peripheral blood mononuclear cells, the concentmtions of IL-1β in peripheral blood plasma and the numbers of EPCs in the peripheral blood were compared between groups using with Student's t lest. Results The level of p38MAPK phosphorylation was more augmented and the concen-tration of IL-1β higher in peripheral blood mononuelear cells and plasma from MODS pigs compared with those from control pigs; nevertheless the mauler of EPC conspicuously decreased in the peripheral blood (P <0.01). The morbidity rate in the MODS group was much higher than that in the control group (P < 0.01). There were fewer EPCs in the peripheral blood of animals in group M than in the peripheral blood of animals in group C (P <0.01). Conclusions p38MAPK phosphorylation is important for the pathogenesis of MODS. p38MAPK phospho-rylation might cause the concentration of IL-1β in the peripheral blood plasma to rise and could cause a drop in the numbers of EPCs, thereby aggravating the inflanmmatory reaction in MODS.     

吡格列酮对高糖培养大鼠肾小球系膜细胞p38丝裂原活化蛋白激酶和转化生长因子β-1的影响

目的观察吡格列酮(PIO)对高糖(HG)培养的肾小球系膜细胞(MCs)p38丝裂原活化蛋白激酶(p38MAPK)和转化生长因子β-1(TGF-β1)表达的影响,探讨PIO肾保护作用及机制。方法体外培养MCs,取对数生长期的细胞以2×105/孔的密度接种于6孔细胞培养板,同步化后随机分为正常对照(NG)组、HG组、p38MAPK抑制剂(S)组及PIO(P)组。Western blot测定磷酸化p38MAPK(p-p38)和总p38MAPK(t-p38)蛋白含量,半定量RT-PCR测定细胞TGF-β1 mRNA表达情况。结果与NG组比较,HG组细胞内p-p38MAPK含量和TGF-β1mRNA表达增强(P0.01);与HG组比较,p38MAPK抑制剂显著抑制HG刺激的细胞内p38MAPK活性和TGF-β1表达(P0.05);与HG组比较,P组细胞内上述变化亦明显降低(P0.05),与S组相似;p38MAPK活性和TGF-β1表达呈正相关(r=0.587,P0.01)。结论 PIO可抑制肾小球系膜p38MAPK通路,降低TGF-β1表达,该作用可能与其肾脏保护部分有关。     

白介素-1β在猪多器官功能障碍综合征中对内皮祖细胞的调控

目的 探讨猪多器官功能障碍综合征(MODS)中p38MAPK介导的白介素(IL)～1β对内皮祖细胞(EPC)的数量与功能的调控,从血管内皮祖细胞分化障碍来研究创伤后MODS的发病机制.方法 将30头家猪随机分为MODS组(n=15,M组)、对照组(n=15,C组),采用失血性休克与内毒素血症的"二次打击法"建立猪MODS模型,在体内Western-blot法检测外周血单核细胞p38MAPK的磷酸化变化;ELISA法测定外周血血浆IL-1β的浓度变化;流式细胞仪检测外周血EPC数量的变化;采用x2检验比较M组与C组的MODS发生率,采用成组t检验比较M组与C组的p38MAPK的磷酸化变化、外周血血浆IL-1β的浓度变化与外周血EPC数量的变化.结果 在MODS中外周血单核细胞p38MAPK的磷酸化增强,导致其外周血IL-1β浓度升高,从而使得外周血EPC数量下降,M组MODS的发生率均明显高于C组(P<0.01);M组的外周血单核细胞p38MAPK的磷酸化与外周血血浆IL-1β的浓度明显高于C组(P<0.01);M组外周血EPC数量明显低于C组(P<0.01).结论 在猪MODS的发病机制中,外周血单核细胞内的p38MAPK的磷酸化使血浆IL-1β浓度升高,使EPC的数量下降,致使MODS的炎症反应加重.     

多器官功能障碍综合征患者外周血单个核细胞凋亡的研究

目的观察多器官功能障碍综合征(M ODS)患者外周血单个核细胞(PBM C s)凋亡及其B cl 2和p53的mRNA表达。方法M ODS患者25例为M ODS组,18名健康志愿者为正常对照组。采用流式细胞仪、电子显微镜、荧光显微镜、DNA琼脂糖凝胶电泳法,观察患者确诊48 h内及正常对照组的PBM C s凋亡;采用逆转录聚合酶链反应(RT PCR)检测PBM C s B cl 2和p53的mRNA表达。结果M ODS患者PBM C s出现典型的细胞凋亡形态学改变,其凋亡率明显高于对照组〔(25.4±9.2)%比(15.9±6.8)%,P<0.01〕;M ODS组的PBM C s凋亡细胞数明显高于正常对照组〔(1.040±0.096)个/高倍视野比(0.235±0.028)个/高倍视野,P<0.05〕。M ODS组PBM C s的B cl 2 mRNA表达量明显低于正常对照组(0.11±0.09比0.19±0.06,P<0.05);p53 mRNA表达量明显高于正常对照组(0.45±0.09比0.25±0.12,P<0.05)。结论M ODS患者PBM C s凋亡异常增高,B cl 2 mRNA表达下调,p53 mRNA表达上调。提示M ODS患者存在细胞凋亡异常,凋亡相关基因表达异常。     

多器官功能障碍综合征患者外周血单个核细胞SOCS-1/3表达及与预后的关系研究

目的 了解外周血单个核细胞(PBMCs)中细胞因子信号转导抑制因子-1/3(SOCS-1/3)表达与多器官功能障碍综合征(MODS)预后的关系.方法 选择32例MODS患者和24例健康志愿者.采用淋巴细胞分离密度梯度离心法分离PBMCs,分别以逆转录-聚合酶链反应及蛋白质免疫印迹法检测PBMCs中SOCS-1/3的mRNA及蛋白表达,分析其与预后及MODS评分的关系.结果 MODS组SOCS-1 mRNA表达与正常组比较差异无统计学意义(0.526±0.044比0.466±0.047,P＞0.05),而SOCS-1蛋白表达显著高于与正常组(0.814±0.045比0.479±0.021,P＜0.05);MODS组中死亡者SOCS-1 mRNA表达显著低于存活者(0.487±0.032比0.532±0.028,P＜0.05),蛋白表达显著低于存活者(0.787±0.029比0.838±0.040,P＜0.05);MODS患者SOCS-1的mRNA及蛋白表达与MODS评分均呈显著负相关(r1＝-0.731,r2=-0.526,P均＜0.01).MODS组SOCS-3 mRNA表达显著高于正常组(0.993±0.415比0.461±0.046,P＜0.05),SOCS-3蛋白表达显著高于正常组(0.458±0.033比0.403±0.024,P＜0.05);MODS组中死亡者SOCS-3 mRNA表达显著高于存活者(1.245±0.408比0.805±0.326,P＜0.05),蛋白表达显著高于存活者(0.486±0.021比0.425±0.016,P＜0.05);MODS患者SOCS-3 mRNA表达与MODS评分呈正相关,但不显著(r＝0.468,P＞0.05),SOCS-3蛋白表达与MODS评分呈显著正相关(r=0.783,P＜0.01).结论 MODS中SOCS-1表达可能起到保护组织避免损伤的作用,其表达减少可能提示患者预后不良;SOCS-3的表达可能起损伤作用或增加组织对损伤的易感性,其表达增加可能提示病情严重及预后不良.     

p38丝裂素活化蛋白激酶磷酸化对多器官功能障碍综合征肿瘤坏死因子-α基因表达调控的影响

目的 探讨猪多器官功能障碍综合征(MODS)中p38丝裂素活化蛋白激酶(p38MAPK)磷酸化对肿瘤坏死因子-α(TNF-α)基因表达调控的影响.方法 将30头家猪随机均分为MODS组和对照组,采用失血性休克与内毒素血症的"二次打击法"建立猪MODS模型.采用蛋白质免疫印迹法(Western blotting)检测外周血单核细胞p38MAPK的磷酸化水平,用实时荧光定量聚合酶链反应(PCR)测定TNF-α mRNA表达,用酶联免疫吸附法(ELISA)测定血浆TNF-α浓度.结果 MODS时外周血单核细胞p38MAPK磷酸化明显增强,使TNF-α mRNA表达明显增强、血浆TNF-α浓度显著升高,与对照组比较差异均有统计学意义(P<0.05或P<0.01).结论 在MODS发病机制中,外周血单核细胞p38MAPK磷酸化使TNF-α基因的转录活性明显增强,从而使血浆TNF-α升高,这是MODS时TNF-α生成增加的机制.     

端粒重复序列结合蛋白质1与2在原发性干燥综合征患者外周血单个核细胞中的表达及其临床意义

目的：端粒重复序列结合蛋白质1（telomeric-repeat binding factor-1,TRF1）和端粒重复序列结合蛋白质2（telomeric-repeat binding factor-2,TRF2）基因表达异常在原发性干燥综合征（primary Sjogren＇s,pSS）发病中可能的作用。方法采用实时荧光定量聚合酶链反应（real-time quantitative polymerase chain reaction,RT-qPCR）检测55例pSS患者和41例健康对照者（healthy control,HC）外周血单个核细胞（peripheral blood mononuclear cells,PBMCs）中TRF1和TRF2转录水平,并与临床指标进行相关性分析。结果（1）PBMCs TRF2转录水平在SS组显著高于HC组（0.0047±0.0107vs.0.0026±0.0049,P＝0.001）,而TRF1转录水平在两组表达差异无统计学意义（P＞0.05）。（2）Spearman相关性分析发现在SS组中TRF2与白细胞计数（WBC）（r＝0.309,P＜0.05）、中性粒细胞计数（GR）（r＝0.312,P＜0.05）、补体3（C3）（r＝0.470,P＜0.05）、抗核抗体（ANA）（r＝0.339,P＜0.05）呈显著正相关,TRF1转录水平与TRF2（r＝1,P＜0.01）、WBC（r＝0.316,P＜0.05）、GR（r＝0.313,P＜0.05）、ANA（r＝0.421, P＜0.05）呈显著正相关。结论 TRF2转录水平在SS患者的增高提示其可能参与了SS患者端粒酶激活和端粒缩短的调节;TRF2、TRF1表达水平与 WBC、GR、C3、ANA 呈显著正相关,提示 TRF2、TRF1可能参与了SS炎症免疫调节,且与SS的发病机制有关。加强端粒保护蛋白在SS等自身免疫性疾病的研究有利于进一步阐明这类疾病的发病机制。     

离体肝脏早期缺血再灌注期间p38信号转导途径对TNFα mRNA表达的影响

目的：研究离体肝脏缺血再灌注期间丝裂原活化蛋白激酶（mitogen activated protein kinase,p38MAPK）信号转导途径对肿瘤坏死因子α（tumor necrosis factorα,TNF-α）mRNA表达的影响。方法：建立兔离体肝脏缺血再灌注模型,对照组（n=12）灌注液中不加特异性p38MAPK抑制剂SB202190,抑制组（n=12）灌注液中加入SB202190（浓度为3μmol/L）。分别于肝脏离体前,冷保存末,再灌注10 min、30 min、60 min及120 min时获取离体肝组织标本。应用Western-blot法及免疫沉淀法检测离体肝组织中p38MAPK表达的水平及活性,RT-PCR法检测TNF-αmRNA表达水平。结果：对照组p38MAPK活性在冷保存末及再灌注10 min、30 min、60 min均较离体前和再灌注120 min显著升高（P〈0.01）,也显著高于同时相点的抑制组（P〈0.01）;抑制组p38MAPK活性在组内各时相点的变化无显著性差异（P〉0.05）。两组肝脏于离体前、冷保存末及再灌注10 min及30 min,肝组织中仅有少量TNF-α mRNA表达,组间及组内比较无显著性差异（P〉O．05）;至再灌注60min及120min,对照组TNF-α mRNA的表达水平显著性高于组内其它时相点（P〈0．01）,而抑制组虽然也显著高于组内其它时相点（P〈O．05）,但却显著性低于同时相点对照组的表达水平（P〈O．01）。离体再灌注期间供肝组织中p38MAPK活性与供肝组织内TNF-α mRNA的表达水平呈显著性正相关（r=0．996,P〈0．01）。结论：p38MAPK对TNF-α生成的调节作用层次可能在转录水平,提示p38MAPK信号转导途径对TNF-α mRNA的调节可能是导致离体肝脏缺血再灌注损伤的重要机制之一。     

B淋巴细胞刺激因子及其受体BAFF-R在系统性红斑狼疮患者外周血单个核细胞中的表达及意义

目的 探讨B淋巴细胞刺激因子(Blys)及其受体BAFF-R在系统性红斑狼疮(SLE)患者外周血单个核细胞(PBMCs)中的表达情况及临床意义.方法 应用流式细胞仪技术,检测90例SLE患者PB-MCs中Blys及其受体BAFF-R的表达,并与45例健康志愿者检测结果 进行比较.分析Blys及BAFF-R的表达与SLE病情活动、其他实验指标及自身抗体的关系.结果 ①SEE患者PBMCs中Blys及BAFF-R的表述百分率比健康对照组高(均P<0.001).其中,活动期和稳定期SLE患者Blys和BAFF-R的表达率均高于健康对照组(P<0.001或0.01);活动期和稳定期比较,Blys的表达较高(P<0.05),而BAFF-R的表达无统计学差异.②SLE患者PBMCs中Blys的表达水平与SLE疾病活动指数评分呈正相关(r=0.728,P<0.001),与免疫球蛋白IgG、IgM里正相关(r=0.691,P<0.001和r=0.453,P<0.01),与补体C3、C4呈负相关(r=-0.510,P<0.001和r=-0.312,P<0.05).③抗dsDNA抗体(+)组患者PBMCs中Blys的表达较 dsDNA抗体(-)组高(P<0.01).Clq抗体(+)组患者PBMCs中的表达也较C1q抗体(-)组高(P<0.01).结论 Blys及BAFF-R在SLE外周血单个核细胞中的表达率升高.Blys的表达在一定程度上反映病情的活动,并与自身抗体的产生相关.Blys及其特异性受体BAFF-R可能参与SLE的发病.     

多器官功能障碍综合征患者外周血白三烯B4与p38丝裂原活化蛋白激酶的变化

目的　探讨多器官功能障碍综合征( MODS)患者外周血白三烯B4( LTB4)与p3 8丝裂原活化蛋白激酶( p3 8MAPK)含量的变化及与MODS病情的关系。方法　对2 6例MODS患者进行病情评分,采用酶联免疫吸附法( ELISA)检测血中LTB4与p3 8MAPK含量,并与1 2例健康体检者进行对照。比较MODS患者MODS评分与外周血L TB4和p3 8MAPK的相互关系,及MODS组死亡与存活患者的MODS评分、外周血LTB4与p3 8MAPK含量。结果　MODS患者血清LTB4含量为( 92 3 .96±3 0 8.65) ng/L,明显低于健康对照组( 2 453 .3 1±40 0 .93 ) ng/L( P<0 .0 5) ;MODS患者血清中p3 8MAPK含量为( 1 93 .83±1 0 6.3 2 ) ng/L,与健康对照组( 1 2 4.3 6±84.50 ) ng/L比较差异无显著性( P>0 .0 5)。MODS组中死亡患者的血清L TB4含量为( 4 44 .98±2 0 6.3 0 ) ng/L,明显低于存活患者的( 1 3 3 4 .51±53 0 .3 5) ng/L( P<0 .0 5) ;p3 8MAPK含量为( 2 72 .0 8±2 0 7.3 7) ng/L ,明显高于存活患者( 1 1 5.59±57.99) ng/L ( P<0 .0 5)。结论　MODS晚期病理生理变化与一般炎症反应有所不同。外周血L TB4与p3 8MAPK可作为MODS病情严重程度及预后判断指标。     

p38信号通路参与呼吸机所致肺损伤大鼠高迁移率族蛋白B1的表达

目的 研究p38信号通路在呼吸机所致肺损伤(ventilator-induced lung injury,VILI)大鼠肺组织表达高迁移率族蛋白BI(high mobility group box 1 protein,HMGB1)中的作用.方法健康sD大鼠24只随机分为3组:对照组(A组)不行机械通气,保留自主呼吸;常规通气组(B组)潮气量(Vt)为8mL/kg;大潮气量通气组(C组)Vt为40 mL/kg.机械通气4 h后处死动物,测定支气管肺泡灌洗液中总蛋白水平、白细胞计数以及肺湿干重比值(W/D)和中性粒细胞髓过氧化物酶(MPO)活性.采用Western blot方法检测肺组织HMGB1蛋白和p38激酶活性变化,采用RT-PCR方法检测HMGB1 mRNA的表达.应用单因素方差分析进行不同组别间的比较.结果 通气4 h后,与A组相比,C组总蛋白水平(1.77±0.68)g/L、白细胞计数(106.55±28.17)×10~7 L~(-1)、肺W/D比值(7.16±1.02)、MPO活性(3.94±1.21)U/g、HMGB1蛋白(0.64±0.17)和mRNA(1.17±0.45)表达以及p38激酶活性(0.51±0.12)均明显增加(P<0.05),而B组上述各项指标的变化均无统计学意义(P>0.05).结论大潮气量机械通气可引起大鼠急性肺损伤,p38参与了机械牵张诱导肺组织HMGB1的表达.