| 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-κβsignaling 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: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.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, by Immunohistochemical staining, and the concentration of TNF-αin plasma in addition. Moreover, HE staining was employed to make pathological section of lung.Results:Clinical research:1,Treating results: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.2,Effect on heart: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 score or oxygenation index had significant difference, comparing different associations before and after treatment, whose lung injury were more serious (P>0.05)3,Inflammatory indexes:White blood cell count and body temperature have gradually stabilized to normal, Western group of white blood cells after treatment was lower than Western medicine group, at the 5th and 7th day were significantly different (P<0.05), and the Western group of white blood cells decreased gradually, the point difference was statistically significance (P<0.01). After treatment, no significant difference in body temperature (P>0.05), but the Western group after treatment was lower than Western medicine group, in the normal body temperature range, and treatment group was still higher than normal body temperature range. In the treatment group after treatment, the CRP, ESR compared to the treatment group decreased significantly (P<0.05), and the same group after treatment than before treatment, was statistically significant (P<0.05).Animal experiment:1,Behavior and organ pathology: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.2,Mortality rate comparison:The model group after 24 hours mortality was 35.0%,20.0% of Chinese medicine group, compared with the control group there were significant differences, and the TCM group compared with the model but also between groups was statistically significant, P<0.05.48 hours after the model model group, mortality was 10%,5% TCM group, no significant difference, P> 0.05. With time,48h medicine group and model group were significantly different mortality rate than 24h, P<0.05. Model group, the total mortality rate 55.0%, while the Chinese group only 45.0% of total mortality in the two groups were significantly different, P<0.05.3,TLR4 mRNA expression in Heart: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)4,TNF-αin 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 heart and TNF-αin plasma, r=-0.389, P >0.05.Conclusion:Clinical research:1,Clinical outcomes:Huanglianjiedu Decoction can increase survival rate of MODS patients, and has well protection effect on heart injury. 2,Protecting cardiac function:HJD combined with routine western medicine can protect the cardiovascular system function and promote functional recovery of damaged organs, and thus significantly reduce mortality. The onset time of about one week after treatment, and with the treatment time increases, the more obvious effects.3,Relation with inflammatory indexes:HJD combined with Western medicine to improve the role of inflammatory markers in support of its regulation of inflammatory response by organ function to protect the view MODS.Animal experiment:1,Model making:By intraperitoneal injection of zymosan suspension mouse model of MODS copy is successful, mouse events, performance and organ pathology consistent with previous literature, but the first 24 hours of high mortality and early consideration no effective organ support related.2,Treating effect on heart:HJD MODS animals can reduce mortality, reduce cardiac damage MODS animals.The HJD treatment, can delay the expression of cardiac TLR4mRNA peak is expected to provide a platform for the treatment.3,Possible mechanism in protecting heart:TLR4 expression in the performance of MODS may be decreased with the progress of the disease after the first rising trend, suggesting that the expression of TLR4 may be a negative feedback regulation. Plasma TNF-αconcentration and the severity of MODS and TLR4 expression in heart tissue may not have direct relevance. HJD organ protective effects of MODS, the mechanism is achieved by regulating the expression of TLR4, but the time may be relatively late onset. |
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