The Relationships Between TLR4 And MODS And Therapeutic Effect Of Huanglianjiedu Decoction On Lung Injury In MODS

Objective:Multiple organ dysfunction syndrome (MODS),which has extremely high fatality rate and enormous expense, still has no definite prevention and cure methods.Its pathogenesis hasn't been explained clearly,but it's thought that Toll-like Receptor 4 (TLR4) maybe the initiation factor,causing the occurrence of MODS through the cascade effect by TLR4/NF-Kβsignaling transduction pathway.The application of Huanglianjiedu Decoction, one representative clearing heat and removing toxin prescription,has got encouraging results in the past research.However, there's much difficulty to use herbs for early intervention,as the syndrome types and distributed regularity of MODS aren't clear.The study was designed to observe the relationships between TLR4 and MODS,to evaluate the therapeutic effect of Huanglianjiedu Decoction on lung injury in MODS,to explore preliminarily the syndrome classification regularity of MODS in Chinese Medcine,in order to deep understand the etiology and pathogenesis of MODS both in Western Medicine and Chinese Medicine and select effective treatment,by animal experiment and retrospective analysis of clinical data.Methods:Animal experiment:The experimental animals, MODS exaggerated inflammatory response model in mice,created by zymosan-paraffin suspension intraperitoneal injection,were divided into blank group,model group and herbs group,and killed separately before model making,as well as at the 24th and 48th hour.Then the TLR4 mRNA expression was measured by fluorescence quantitative PCR, NF-κβby Immunohistochemical staining,and the concentration of TNF-αCr,ALT in plasma in addition.Moreover,HE staining was employed to make pathological section of lung.Clinical research:Case observation form was used to do retrospective analysis,including analyzing the syndrome classification regularity by observing the symptoms of MODS patients,and gathering theirs vital signs and laboratory indexes in control group and herb group.Results:Animal experiment:Pathological section of organs:Organs injuries were not orberserved in blank group,yet can be found in both model group and herb group after 24 hours model making,in which the injury ratios of heart and lung were higher,68.8% and 62.5% respectively,but that of intestine was only 5.0%.The changes of lung were mainly on wider alveolar septum, alveolar collapse, erythrocyte infiltration in alveole and so on.TLR4 mRNA expression in lung:TLR4 mRNA expression in blank group first descended then ascended as the time went by (P<0.05).There was same tendency in model group,yet no significance (P>0.05).However,the expression descended continuously in herb group,at the 48th hour it was the lowest during the three groups,either having no significance (P＞0.05)NF-κβexpression in lung:NF-κβdidn't express obviously in blank group,and the expression of model group accounted for 87.0% in "++"and"+++",60.0% in "+++",and that of herb group accounted for 73.0% in "+"and"++",only 20.0% in "+++",having significant difference during groups (P<0.05)Inflammatory factors in plasma:There was no significant difference modeling before and after in blank group,model group and herb group,either no relationship between TLR4 mRNA expression of lung and TNF-αin plasma, r=-0.227, P>0.05.Clinical research:Syndrome analyze in Chinese Medicine:Toxin and Heat Syndrome was in majority during the 18 patients observed(77.8%), but most patients showed complex syndromes,in which Yangming fu-viscera excess syndrome and phlegm excess syndrome were the main accompanying syndromes,reaching 85.7%,yet heat forcing blood-out syndrome occurred less (21.4%),and blood stagnation syndrome only 16.7%,acute deficiency syndrome only 5.6%.Organs dysfunction distribution:The ratio of three organs injured at the same time is the most(38.9%), and mortality rate of two organs injured simultaneously is the largest (80.0%), followed by three organs at the same time (71.8%). During the seven organs and systems,dysfunctions in lung, gastrointestine tract and nervous system were largest, respectively 88.9%,88.9% and 83.3%,followed by kidney and circulation system,66.7% and 61.1%,and liver dysfunction appeared lowest,only 27.8%.The following three associations of lung and circulation and gastrointestine and liver and kidney,lung and circulation and gastrointestine,lung and kidney occur more often than other ones among MODS patients whose lung injury is more serious.Indexes comparison:Oxygenation index descended by 29.79mmHg in control group after treatment,yet no significant difference (P> 0.05), while in herb group ascended by 90.66mmHg,near normal(300 mmHg), significantly different to control group (P<0.05) Neither APACHEⅡscore or oxygenation index had significant difference, comparing different associations before and after treatment,whose lung injury were more serious (P> 0.05)Conclusion:1. TLR4 expression in MODS can ascend after descend with the disease progressing,which may cost by the TLR4 negative feedback effetion. NF-κβexpression has positive correlation with MODS seriousness,controlled by Huanglianjiedu Decoction.And TNF-a changes in plasma doesn't have directive relationship with MODS seriousness,either TLR4 expression in lung.2. Huanglianjiedu Decoction can lower the animal mortality rate,lighten lung injury in MODS animal.That's maybe because it can reduce TLR4 expression.3. Heat and toxin syndrome is the main syndrome,always occurring as compound syndrome, in MODS early stage during those whose lung injury is more serious, and Yangming fu-viscera excess syndrome is not main syndrome but accompanying one.4. The high frequency syndrome may be a more reliable index to evaluating the organs function, so pay more attention to high frequency syndrome can help us realize organs dysfunction opportunely. APACHEⅡscore can't have direct relationship with MODS prognosis.5. Huanglianjiedu Decoction can increase survival rate of MODS patients mainly on lung injury,and has well protection effect on lung injury.