Effect Of Jiawei Huanglian Jiedu Decoction On Regulation Of Toll-like Receptor 4 In Multiple Organ Dysfunction Syndrome

Background:With medical advances and higher cure rate of critically ill patients, multiple organ dysfunction syndrome (MODS) has become the biggest challenge in critical care medicine due to its complex causes, difficult prevention and treatment and extremely high mortality. How to reduce morbidity and mortality of MODS is a key issue of research in China and aboard. Due to the complex pathogenesis of MODS, the inflammatory reaction theory is the foundation. The research on Toll-like receptor signal pathway and inflammatory reaction is in increasing depth during the past 20 years. Studies have shown that infectious factors and non-infectious factors can mediate the activation of Toll-like receptor 4 (TLR4), which can release NF-KB factor into the nucleus to activate gene transcription network then to start the inflammatory cascade reaction, leading to MODS finally.Modern 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. Domestic research also shows that Chinese herbal that can remove the toxin as well as heat and Dahuang have anti-inflammatory and sterilization effect, together with function to decline translocation of bacteria and endotoxin from the gut. Jiawei 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 mortalityObjective:1. To observe effect of Jiawei Huanglian Jiedu Decoction on expression of Toll-like receptor 4 from mononuclear cells in peripheral blood of MODS patients, which is in order to learn more about effect mechanism of Jiawei Huanglian Jiedu Decoction on MODS by regulating Toll-like receptor 4. 2. To observe effect of Jiawei Huanglian Jiedu Decoction on APACHEⅢscore and the clinical indexes together with laboratory indexes in MODS patients, which is in order to probe its efficacy on MODS and organ protection, including to provide the basis of Traditional Chinese Medicine on curing MODS in clinical application.Methods:22 patients were involved in the research who met the inclusion criteria in ICU of the first affiliated hospital of Guangzhou University of Traditional Chinese Medicine from June 2008 to October 2009. The patients were divided into 2 groups randomly, patients in treatment group were treated by Jiawei Huanglian Jiedu Decoction combined with western medicine, patients in controlled group were treated with western medicine alone. Toll-like receptor 4 protein levels, body temperature, heart rate, mean arterial pressure, WBC count, PO2/FIO2, PH value of blood, dopamine concentration,24-hour urine volume, Creatinine, platelets, INR and the change in APACHEⅢscore were monitored from patients who diagnosis MODS, which the first monitor time is within 24h before treatment, the second monitor time is the third day since treatment, and the third monitor time is the fifth day since treatment. The incidence of gastrointestinal bleeding and toxic intestinal obstruction, as well as Glasgow score were recorded within 24h before treatment and the fifth day since treatment. The incidence of single organ dysfunction, ICU stay time and expenses in ICU, the cost of mechanical ventilation, time of using mechanical ventilation, improvement rate, mortality, culture results of blood, phlegm, urine and stool, the incidence of Traditional Chinese Medicine type were recorded, which would be counted and analyzed in all.Results:1. The improvement rate of Zhong-xi group was 75.0%, mortality rate was 16.7%, the improvement rate of Xi-yi group was 30.0%, mortality rate was 50.0%. 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).2. With extension of treatment, the score of APACHEⅢand the percentage of TLR4 expression from Zhong-xi group had a gradual downward trend, the time difference was statistically significant (P<0.05), the Xi-yi group had no obvious downward trend in contrast. The percentage of TLR4 expression from Zhong-xi group were significantly lower than which from the Xi-yi group. And the difference was statistically significant (P<0.01). The correlation between TLR4 and APACHEⅢscore was 0.732, and they were in a positive correlation.3. The incidence of respiratory system dysfunction, central nervous system dysfunction and cardiovascular system dysfunction were much high in MODS patients. The incidence of respiratory system dysfunction was 77.27%, and the incidence of cardiovascular system dysfunction was 77.27%, together with central nervous system dysfunction 72.73%.And next followed by renal system dysfunction and blood system dysfunction, but incidence of hepatic system dysfunction was the lowest.4. After treatment in Zhong-xi group, the body temperature, heart rate, mean arterial pressure, blood PH value, platelets, INR, white blood cell count have gradually stabilized to normal, PO2/FIO2, urine volume have gradually increased, dopamine concentration and creatinine have gradually reduced, in which white blood cells, blood PH value, heart rate, mean arterial pressure, dopamine, PO2/FIO2 among various time points were statistically significant (P＜0.05). Although there was change in Xi-yi group, but its improvement was marginal, some organ system dysfunction have deteriorated, which among various time points were not statistically significant.5. 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). The GCS score of Zhong-xi group was lower than the Xi-yi group after treatment, The GCS score difference before and after treatment between two groups was statistically significant (P＜0.01).6. The gram-negative bacteria infection rate of Zhong-xi group was 41.67%, Gram-positive infection rate was 16.67%, fungal infection rate was 16.67%, the rate that was no bacteria detected was 25.0%. The gram-negative bacteria infection rate of Xi-yi group was 60.0%, Gram-positive infection rate was 20.0%, fungal infection rate was 10.0%, the rate that was no bacteria detected was 10.0%. 7. The incidence of ICU stay time and expenses in ICU, the cost of mechanical ventilation, time of using mechanical ventilation were not statistically significant in all.8. The incidence of "toxin combined with heat" type was 54.5% in all cases. The "toxin combined with heat" type had a higher incidence.Conclusion:1. Jiawei Huanglian Jiedu Decoction combined with western medicine in treating MODS could improve patients'condition, and the mortality of Zhong-xi group significant debased. The treatment effect was much better than that were treated by western medicine alone, and as the treatment time prolonged, the effect was much better.2. TLR4 expression and APACHEⅢscore were in a positive correlation. It showed that probably with up regulation of TLR4 expression, thus it promote much more secretion of inflammatory factors which mediate uncontrolled inflammatory response, leading to MODS, or even making MODS deteriorated. The effect of Jiawei Huanglian Jiedu Decoction on MODS patients may lie on regulating down TLR4 expression from mononuclear cell to control the uncontrolled inflammatory response, therefore to reduce the mortality of MODS significantly.3. The incidence of respiratory system dysfunction and cardio system dysfunction were the highest. Jiawei Huanglian Jiedu decoction combined with western medicine could protect the function of cardio system, respiratory system, renal system, gastrointestinal system and central nervous system, and promote recovery of damaged organs, therefore to reduce the mortality significantly. As the treatment time prolonged, the effect was much better.4. The cases of Non-negative bacteria and of that was no bacteria detected could still show high expression of TLR4 protein levels, which may be related to translocation of bacterial and endotoxin from gut. 5. 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 Medicine. 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.