肠源性内毒素血症与器官功能状态相关性的研究
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摘要
【目的】进一步了解肠源性内毒素血症的特点和在外科危重病中的变化规律,以及它与器官功能、免疫状态和预后的相关性。以求将来对肠源性内毒素血症的防治有所帮助。
【方法】对41例外科危重病人进行前瞻性观察,当合并肠功能障碍和MODS时,观察APACHEⅡ评分、器官功能损害数目、血内毒素水平,及转归情况。分别从不同角度按年龄、APACHEⅡ评分及预后分组,观察内毒素血症水平的差异,病死率及细胞因子,免疫状态的特点。同时给予中西医结合治疗,动态观察治疗前、治疗后3天和7天的尿L/M、内毒素、Th1/Th2及HLA-DR的变化规律。
【结果】①各病种之间,APACHEⅡ评分、器官功能损害数目、内毒素水平、病死率均无显著差异(p＞0.05),所有病例的内毒素水平均高于正常值;②各功能受损之器官或系统中,除肠功能障碍外,以肺脏居首;③各年龄组之间,内毒素水平无显著差异(p＞0.05),但APACHEⅡ评分、器官损害数目和病死率均有显著差异。年龄是外科危重病死亡的独立危险因素;④不同的危重程度比较,各组器官损害数目、WBC计数、尿L/M值、内毒素水平、细胞因子、免疫状态及死亡率多数均有显著差别;⑤按预后分组,治愈组和存活组的L/M、内毒素水平在治疗后7天均有下降,有统计学意义,而死亡组的L/M、内毒素水平有显著升高。治愈组的Th1/Th2漂移在治疗后3天和7天均有统计学意义,存活组的Th1/Th2在治疗后7天下降有统计学意义,而动态观察死亡组的Th1/Th2,第3天即有明显的下降趋势,第7天显著低于正常值。HLA-DR于治疗后3天的变化无统计学意义,第7天治愈组的升高有统计学意义,而死亡组HLA-DR值则显著降低。
【结论】在严重的创伤、手术等应激状态下,肠道容易受到感染、缺血或缺血再灌注等因素的打击,导致肠屏障功能的损害,细菌和内毒素移位,形成肠源性内毒素血症,继而引发SIRS、脓毒症和MODS。本试验观察到,肠源性内毒素血症与危重程度、肠屏障损害程度及预后密切相关。其早期与Th1/Th2呈正相关,随着中西医结合治疗进程内毒素水平可以逐渐降低、免疫状态得以恢复,出现Th1向Th2漂移,并趋于平衡,HLA-DR表达逐渐恢复,预后良好。但如果病情进行性恶化,出现重度脓毒症(severe sepsis,SS),甚至免疫衰竭时,Th1/Th2往往表现为Th2表达优势,抗炎症反应过度,HLA-DR表达极度低下,免疫功能抑制,同时内毒素水平进行性升高,最终导致无法控制的脓毒症和MODS,以致死亡。因此,在疾病发展与治疗进程中,器官损害数目的增加,内毒素水平、尿L/M的进行性升高、Th1/Th2显著降低和单核细胞表面HLA-DR表达低下均是判断预后不良的重要指标。另外,在外科危重病治疗中要重视内毒素血症对机体的序贯损害,注意及时调节机体的免疫功能,重视中医药对调节免疫、清除内毒素、保护脏器功能的作用。中西医结合治疗将是肠源性内毒素血症防治的发展方向。
[Objective]To further explore the characteristics and the changing regularity of the intestinal endotoxemia in critical patients.To investigate the relationship between the intestinal endotoxemia and the state of system organ's function and immunity. From this study we wish to improve our prevention and treatment to critical patients with the intestinal endotoxemia to some extent.
[Methods]41 samples of critical surgical patients suffering from gut dysfunction and MODS in SICU were prospective observed.When it combines with the intestinal dysfunction and the multiple organ dysfunction syndrome(MODS),we observe the APACHE-Ⅱscore,the number of the organs with the functional lesions,the level of the endotoxin in the blood,and the condition of turnover.The patients are divided into groups on the basis of their age,APACHE-Ⅱscore and prognosis,and then we observe the difference of the level of the Endotoxemia,mortality and the characteristics of the cytokine and immune state.At the same time,the patients were treated with the combination of the TCM and Western medicine,an then we observe the changing rule of the L/M in the urine,endotoxin,Th1/Th2 and HLA-DR before the treatment and on the 3rd and 7th days after being treated.
[Result]①Among all the kinds of diseases,the.APACHE-Ⅱscore,the number of the organs with the functional lesions,the level of the endotoxin in the blood,and mortality bear no significant deviations(p＞0.05),and the level of endotoxin of all the patients is higher than the normal level;②Among the organs and systems with functional damage,the lung stays in the first plays except the intestine;③Among the age groups,the level of the endotoxin has no big difference(p＞0.05), but there are obviously difference among the APACHE-Ⅱscore,the number of the organs with the functional lesions,and mortality.The age is a independent risk factor for the mortality of the surgical critical diseases;④The comparison of the different severities finds that the number of the organs with the functional lesions,the number of WBC,the L/M in the urine,the level of the endotoxin,the cytokine,the immune state and the mortality almost have clear diferences;⑤If the groups are divided on the basis of prognosis,the L/M and the level of the endotoxin of the curing group and survival group descengs on the 7th day after being treated,and it bears statistical significances,but the L/M and the level of the endotoxin of the death group raises obviouely.The migration of the Th1/Th2 of the curing group have statistical significances on the 3rd and 7th day after being treated,and the descending of the Th1/Th2 in the survival group has statistical significances on the 7th day after being treated.However,the dynamic observation of the Th1/Th2 in the death group indicates that it has a clear downtrend on the 3rd day,and it is obviously lower than the normal value on the 7th day.The changing of HLA-DR on the 3rd day has no statistical significance,and the increasing of the curing group on the 7th day has statistical significances,but the HLA-DR of the death group descends significantly.
[Conclusion]In the stress state,such as the severe trauma,surgery and so on, the intestinal tract is liable to be attacked by the factors of infections,ischemia or reperfusion and so on,which leads to the damage of the intestinal barrier function,the translocation of the bacterium and endotoxin.All the above form the intestinal endotoxin,and initiate SIRS,sepsis and MODS subsequently.This research finds that the intestinal endotoxin has a close relationship with the severity,the degree of the lesion of the intestinal barrier,and the prognosis.In the early stage,it has a positive correlation with the Th1/Th2,and following the combined treatment of the TCM and Western medicine,the level of the endotoxin can be lowered,and the immune state can also be regulated,and then the Th1 migrates to Th2,which goes to a balance. The expression of HLA-DR recovers gradually,and the prognosis is fine.However,if the pathologic condition aggravates unceasingly,when the severe sepsis and the immune failure appear,the Th1/Th2 and HLA-DR always descend to the utmost,and the anti-inflammatory response overacts,which leads to the depression of the immune function.The level of the endotoxin raises unceasingly,which induce to the uncontrolled sepsis,MODS,or even death.For this reason,we should pay attention to the continuous damage of the endotoxemia in the surgical critical diseases,and regulate the immune function in time.We should think highly of the functions of the traditional Chinese medicine,such as regulating the immune function,removing the endotoxin and protect the organs' function.The combined treatment of the TCM and Western medicine is to be the developing direction of the prevention and cure of the intestinal endotoxemia.
【方法】对41例外科危重病人进行前瞻性观察,当合并肠功能障碍和MODS时,观察APACHEⅡ评分、器官功能损害数目、血内毒素水平,及转归情况。分别从不同角度按年龄、APACHEⅡ评分及预后分组,观察内毒素血症水平的差异,病死率及细胞因子,免疫状态的特点。同时给予中西医结合治疗,动态观察治疗前、治疗后3天和7天的尿L/M、内毒素、Th1/Th2及HLA-DR的变化规律。
【结果】①各病种之间,APACHEⅡ评分、器官功能损害数目、内毒素水平、病死率均无显著差异(p＞0.05),所有病例的内毒素水平均高于正常值;②各功能受损之器官或系统中,除肠功能障碍外,以肺脏居首;③各年龄组之间,内毒素水平无显著差异(p＞0.05),但APACHEⅡ评分、器官损害数目和病死率均有显著差异。年龄是外科危重病死亡的独立危险因素;④不同的危重程度比较,各组器官损害数目、WBC计数、尿L/M值、内毒素水平、细胞因子、免疫状态及死亡率多数均有显著差别;⑤按预后分组,治愈组和存活组的L/M、内毒素水平在治疗后7天均有下降,有统计学意义,而死亡组的L/M、内毒素水平有显著升高。治愈组的Th1/Th2漂移在治疗后3天和7天均有统计学意义,存活组的Th1/Th2在治疗后7天下降有统计学意义,而动态观察死亡组的Th1/Th2,第3天即有明显的下降趋势,第7天显著低于正常值。HLA-DR于治疗后3天的变化无统计学意义,第7天治愈组的升高有统计学意义,而死亡组HLA-DR值则显著降低。
【结论】在严重的创伤、手术等应激状态下,肠道容易受到感染、缺血或缺血再灌注等因素的打击,导致肠屏障功能的损害,细菌和内毒素移位,形成肠源性内毒素血症,继而引发SIRS、脓毒症和MODS。本试验观察到,肠源性内毒素血症与危重程度、肠屏障损害程度及预后密切相关。其早期与Th1/Th2呈正相关,随着中西医结合治疗进程内毒素水平可以逐渐降低、免疫状态得以恢复,出现Th1向Th2漂移,并趋于平衡,HLA-DR表达逐渐恢复,预后良好。但如果病情进行性恶化,出现重度脓毒症(severe sepsis,SS),甚至免疫衰竭时,Th1/Th2往往表现为Th2表达优势,抗炎症反应过度,HLA-DR表达极度低下,免疫功能抑制,同时内毒素水平进行性升高,最终导致无法控制的脓毒症和MODS,以致死亡。因此,在疾病发展与治疗进程中,器官损害数目的增加,内毒素水平、尿L/M的进行性升高、Th1/Th2显著降低和单核细胞表面HLA-DR表达低下均是判断预后不良的重要指标。另外,在外科危重病治疗中要重视内毒素血症对机体的序贯损害,注意及时调节机体的免疫功能,重视中医药对调节免疫、清除内毒素、保护脏器功能的作用。中西医结合治疗将是肠源性内毒素血症防治的发展方向。
[Objective]To further explore the characteristics and the changing regularity of the intestinal endotoxemia in critical patients.To investigate the relationship between the intestinal endotoxemia and the state of system organ's function and immunity. From this study we wish to improve our prevention and treatment to critical patients with the intestinal endotoxemia to some extent.
[Methods]41 samples of critical surgical patients suffering from gut dysfunction and MODS in SICU were prospective observed.When it combines with the intestinal dysfunction and the multiple organ dysfunction syndrome(MODS),we observe the APACHE-Ⅱscore,the number of the organs with the functional lesions,the level of the endotoxin in the blood,and the condition of turnover.The patients are divided into groups on the basis of their age,APACHE-Ⅱscore and prognosis,and then we observe the difference of the level of the Endotoxemia,mortality and the characteristics of the cytokine and immune state.At the same time,the patients were treated with the combination of the TCM and Western medicine,an then we observe the changing rule of the L/M in the urine,endotoxin,Th1/Th2 and HLA-DR before the treatment and on the 3rd and 7th days after being treated.
[Result]①Among all the kinds of diseases,the.APACHE-Ⅱscore,the number of the organs with the functional lesions,the level of the endotoxin in the blood,and mortality bear no significant deviations(p＞0.05),and the level of endotoxin of all the patients is higher than the normal level;②Among the organs and systems with functional damage,the lung stays in the first plays except the intestine;③Among the age groups,the level of the endotoxin has no big difference(p＞0.05), but there are obviously difference among the APACHE-Ⅱscore,the number of the organs with the functional lesions,and mortality.The age is a independent risk factor for the mortality of the surgical critical diseases;④The comparison of the different severities finds that the number of the organs with the functional lesions,the number of WBC,the L/M in the urine,the level of the endotoxin,the cytokine,the immune state and the mortality almost have clear diferences;⑤If the groups are divided on the basis of prognosis,the L/M and the level of the endotoxin of the curing group and survival group descengs on the 7th day after being treated,and it bears statistical significances,but the L/M and the level of the endotoxin of the death group raises obviouely.The migration of the Th1/Th2 of the curing group have statistical significances on the 3rd and 7th day after being treated,and the descending of the Th1/Th2 in the survival group has statistical significances on the 7th day after being treated.However,the dynamic observation of the Th1/Th2 in the death group indicates that it has a clear downtrend on the 3rd day,and it is obviously lower than the normal value on the 7th day.The changing of HLA-DR on the 3rd day has no statistical significance,and the increasing of the curing group on the 7th day has statistical significances,but the HLA-DR of the death group descends significantly.
[Conclusion]In the stress state,such as the severe trauma,surgery and so on, the intestinal tract is liable to be attacked by the factors of infections,ischemia or reperfusion and so on,which leads to the damage of the intestinal barrier function,the translocation of the bacterium and endotoxin.All the above form the intestinal endotoxin,and initiate SIRS,sepsis and MODS subsequently.This research finds that the intestinal endotoxin has a close relationship with the severity,the degree of the lesion of the intestinal barrier,and the prognosis.In the early stage,it has a positive correlation with the Th1/Th2,and following the combined treatment of the TCM and Western medicine,the level of the endotoxin can be lowered,and the immune state can also be regulated,and then the Th1 migrates to Th2,which goes to a balance. The expression of HLA-DR recovers gradually,and the prognosis is fine.However,if the pathologic condition aggravates unceasingly,when the severe sepsis and the immune failure appear,the Th1/Th2 and HLA-DR always descend to the utmost,and the anti-inflammatory response overacts,which leads to the depression of the immune function.The level of the endotoxin raises unceasingly,which induce to the uncontrolled sepsis,MODS,or even death.For this reason,we should pay attention to the continuous damage of the endotoxemia in the surgical critical diseases,and regulate the immune function in time.We should think highly of the functions of the traditional Chinese medicine,such as regulating the immune function,removing the endotoxin and protect the organs' function.The combined treatment of the TCM and Western medicine is to be the developing direction of the prevention and cure of the intestinal endotoxemia.
引文
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