Effect Of Huanglian Jiedu Decoction On Regulation Toll-like Receptor4in Gastrointestinal Of Mods

BackgroundMultiple organ dysfunction syndrome (MODS), which has extremely high fatality rate and enormous expense, still has no definite prevention and cure methods. How to reduce morbidity and mortality of MODS has become the biggest Challenge in critical care medicine. Due to the complex pathogenesis of MODS,Its pathogenesis hasn’t been explained clearly, but it’s thought that Toll-like Receptor4(TLR4) maybe the initiation factor, causing the occurrence of MODS through the cascade effect by TLR4/NF-кβ signaling transduction pathway.Today Traditional Chinese Medicine consider that the initiating infectious and non-infectious causes of MODS are similar to the "toxin" and "heat", in Traditional Chinese Medicine. 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. Huanglian Jiedu Decoction is likely to regulate inflammatory mediators in inflammatory pathways effectively which to play a unique role in prevention together with cure of MODS, and reducing its mortality.Objective1、To probe effect of Huanglian Jiedu Decoction on MODS and organ protection, including to provide the basis of Traditional Chinese Medicine on curing MODS in clinical application.2、To probe the possible pathogenesis of MODS, to observe effect of Huanglian Jiedu Decoction on expression of TLR4and TNF-α, which is in order to learn more about effect mechanism of Huanglian Jiedu Deeoetion on MODS by regulating TLR4.MethodsClinical research:32patients were involved in the researeh who met the inclusion criteria in ICU of the first affiliated hospital of Guangzhou University of Traditional Chinese Medicine from September2009to March2012. The patients were divided into2groups randomly, patients in treatment group were treated by Huanglian Jiedu Decoction combined with western medicine, patients in controlled group were treated with western medicine alone. bodytemperature, WBC count, CRP, ESR, APACHEIII score were monitored from patients who diagnosis MODS, which the first monitor time is within24h before treatment, the seeond monitor time is the third day since treatment, and the third monitor time is the fifth day since treatment, the fourth monitor time is the seventh day since treatment. The incidence of gastrointestinal bleeding and toxic intestinal obstruction, were recorded with in24h before treatment and the fifth day since treatment. ICU stay time and expenses in ICU, time of using mechanical ventilation, the incidence of Traditional Chinese Medicine type were recorded, whieh would be counted and analyzed in all. 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 the24th and48th hour. Then the TLR4mRNA expression was measured by fluorescence quantitative PCR, by Immunohistochemical staining, and the concentration of TNF-a in plasma in addition. Moreover, HE staining was employed to make pathological section of intestine.ResultsClinical research:1、The improvement rate of Zhong—xi group was87.5%, mortality rate was12.5%, the imrpovement rate of Xi—yi group was50.0%, mortality rate was50.0%. The improvement rate of Zhong—xi group was significantly higher than Xi—yi group (P<0.05), and the mortality rate was significantly lower than the Xi—yi group (P<0.05). With extension of treatment, the score of APACHEIII from Zhong—xi group had a gradual downward trend, compare the fifth day and the seventh day, the time difference was statistically significant(P<0.05). 2、The incidence rate of toxic intestinal obstruction of Zhong—xi group was50.0%and drop down to12.5%after the treatment, the ineidenee rate of gastrointestinal bleeding of Zhong—xi group was43.75%and drop down to12.5%after the treatment. The incidence rate of toxic intestinal obstruction of Xi—yi group was43.75%and drop down to37.5%after the treatment, the incidence rate of gastrointestinal bleeding of Xi—yi group was37.5%and drop down to31.25%after the treatment. The incidence of gastrointestinal system dysfunction of Zhong—xi group was significantly lower than Xi—yi group after treatment, the difference between two groups was statistically significant (P<0.05).3、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 the5th and7th 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).4、The incidence of "toxin combined with heat" type was58.38%in all cases. The ""toxin combined with heat" type had a higher incidence. Animal experiment:1、Behavior and organ pathology:Before model making, Organs injuries were not orberserved, yet can be found in both model group and herb group after24hours model making. we can see the hyperemia and the hydroncus in the intestinal mucosa and the intestinal submucosa, which the herb group is better than the model group.2、The model group after24hours mortality was35.0%,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).48hours after the model model group, mortality was10%,5%TCM group, no significant difference, P>0.05. With time, 48h medicine group and model group were significantly different, mortality rate than24h(P<0.05). Model group, the total mortality rate55.0%, while the Chinese group only45.0%of total mortality in the two groups were significantly different (P<0.05).3、TLR4mRNA expression in Intestinal:TLR4mRNA 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 the48th hour it was the lowest during the three groups, either having no significance (P>0.05)4、TNF-α in plasma:There was no significant difference modeling before and after in blank group, model group and herb group, either no relationship between TLR4mRNA expression of heart and TNF-α in plasma, r=-0.419, P>0.05.ConclusionClinical research:1、Huanglian Jiedu Decoction can increase improvement rate of MODS patients, and decrease the mortality rate. The treatment effect was much better than that were treated by western medieine alone.2、Huanglian Jiedu Decoction combined with routine western medicine can decrease the incidence rate of gastrointestinal dysfunction, and protect the function of gastrointestinal system, and promote recovery of damaged organs,therefore to reduce the mortality significantly.3、 Between the32patients, the "toxin combined with heat" type had higher incidence that other types. It showed that "toxin combined with heat" type are major type of MODS type of Traditional Chinese Medcine. The Pathogenesis mechanism of MODS was caused by the lesion of toxin—heat pathogen collected and tied in Qi—blood and the splanchinic organs according to the Pathogenesis mechanism of Traditional Chinese Medicine, which provide the basis for using method of removing heat and toxin by herbal to prevent MODS as well as treat MODS.Animal experiment:1、Huanglianjiedu Decoction can reduce mortality of MODS animals, reduce gastrointestinal damage MODS animals. The HJD treatment, can delay the expression of gastrointestinal TLR4mRNA.2、TLR4expression in the performance of MODS may be decreased with the progress of the disease after the first rising trend, suggesting that the expression of TLR4may be a negative feedback regulation. Plasma TNF-a concentration and the severity of MODS and TLR4expression in intestine tissue may not have direct relevance. HJD organ protective effects of MODS, the mechanism is achieved by regulating the expression of TLR4.