Effects Of Jiawei Huanglian Jiedu Decoction On Regulation Of NF-κB Pathway In Multiple Organ Dysfunction Syndrome

ObjectiveWith the medical progress and higher cure rate of other critically ill patients,the threats of Multiple Organ Dysfunction Syndrome(MOPS)are highlighted increasingly,has become prominently fatal cause of critically ill patients in ICU,the severest complication of trauma and infection.At present it is a new put-forward practical important research issue which appears in modern Emergency Medicine.MODS has complex causes, difficult prevention and treatment and extremely high mortality,is a research hotspot attracted by the international medical field now,which is also the most direct and important cause of death in patients with benign diseases.So,how to improve its level of the early diagnosis and treatment is of great urgency.Due to the complex pathogenesis of MODS, the inflammatory reaction theory is the foundation and the intestinal motility theory is one of the mechanisms of systemlc excessive inflammation reaction.The simultaneous use of Huanglian Jiedu Decoction,which has clear anti-inflammatory effect,and Dahuang,which declines the rate of translocation of bacteria and endotoxin from the gut, shows the therapeutic potential in MODS.The objective of this study was focused on two aspects:①To observe the therapeutic effect of Chinese medicine Huanglian Jiedu Decoction and Dahuang in treating MODS by APACHEⅢscoring,SPSS14.0 was used to analyze the mortality of MODS patients.Observe the therapeutic effect by using Huanglian Jiedu Decoction and Dahuang in treatment of MODS in order to seek for the effective treatment to MODS.②To observe the protective effects of Huanglian Jiedu Decoction and Dahuang on organ function and structure in rats with MODS,to explore the molecular mechanism of Huanglian Jiedu Decoction in preventing and treating MODS.Method1.We conducted a prospective case-control study with 48 MODS patients in ICU during August 2005 to May 2008.23 patients in treatment group were treated with western medicine combined Jiawei Huanglian Jiedu Decoction,25 patients in controlled group were treated with western medicine alone.Patients' clinical situation and outcome were observed by APACHEⅢscoring.To study the therapeusis gastrointestinal tract,peripheral circulation and heart effects of Huanglian Jiedu Decoction with MODS.2.The animal models of MODS were induced by intraperitoneal injection of zymosan and the Jiawei Huanglian Jiedu Decoction was given orally.Thrity-six male Sprage Dawely rats were divided randomly into blank,model and Chinese medicine groups.It is investigated by the methods of physics,bio-chemical,immunohistochemistry and pathology applied.The items include the behavior,body temperature,breath,the heart rate,GPT, Cr,NF-κB,NO,NOS among the blood plasma,intestine,heart,and pathology of intestine and heart is examined too.3.The results of all data were shown in the form of(?)±SD and were dealed with using SPSS14.0 programs of statistics.The relation of data between two groups were compared using standard t-test.Meanwhile the relation of data among several groups were compared using F test.Pairwise comparison in multiple groups was conducted with LSD method.The numeration data were analyzed using Chi-square test and rank sum test. p＜0.05 was considered statistically significant.Results:1.Clinical case analysis1.1 Among the 48 patients,there are 35 cases of survival while 13 cases of death.APACHEⅢscore of patients in death group are higher than those in survive group since patients entering the ICU,which indicated that the clinical conditions of patients in death group were more severe.The point of APACHEⅢin dead group was significantly higher than that in survival group after treatment(P＜0.05).1.2 After treatments,APACHEⅢscore of Zhong-xi group patients decreased,the therapeutic effects of Zhong-xi group were more significant than those in western medicine group(P＜0.05),the mortality being 13.04%(Zhong-xi group)and 40%(western medicine group).1.3 Incidence of the gastrointestinal tract and peripheral circulation failure was higher than that of heart failure.After treatment,Jiawei Huanglian Jiedu Decoction reduced the incidence of the gastrointestinal tract and peripheral circulation failure,there was significant differences compared with model group(P＜0.05).But there was no significant differences between two groups in reducing the heart failure(P＜0.05).2.Experimental study on animal model of MODS2.1 The rats model of MODS induced by injecting the belly cavity with the mix liquid of zymosan-paraffin were successful,and matched the diagnostic criteria of MODS animal model.Also,the rat model of MODS showed the effect of toxin-heat-pathogen collected and tied in the splanchnic organs is the physiopathogenic mechanism of TCM about MODS.2.2 Compare with the blank group,the levels of NO,iNOS in serum,intestine and heart in model group were all increased,whilehe levels of cNOS in serum,intestine were significantly drceased(P＜0.05).After treatment With Jiawei Huanglian Jiedu Decoction,the levels the levels of NO,iNOS in serum,intestine were decreased as compared with those in model group,as well as the level of cNOS increased(P＜0.05);the level of NO in heart was drceased too(P＜0.05),but the levels of iNOS and cNOS were not significantly changed(P＞0.05).2.3 The pathology change of intestine and heart in Chinese medicine group was more relief than that in model group.Compared with the blank group, the expression of intestine NF-κB in model group was increased(P＜0.05). After treatment with Jiawei Huanglian Jiedu Decoction,the expression of intestine NF-κB was significantly decreased as compared with those in model group(P＜0.05).While the expression of heart NF-κB in model group was not significantly increased as compared with the blank group(P＞0.05).Conclusion:1.APACHEⅢscore was not only good to interpret critical condition of MODS,but also well in calibration overall mortality predition.2.Jiawei Huanglian Jiedu Decoction combined with western medicine in treating MODS could improve patients' condition,lead to the lowing of APACHEⅢscores,the mortality of Jiawei Zhong-xi group significant debased.3.Jiawei Huanglian Jiedu Decoction had different effects on treating different organ dysfunction,it was better at treating gastrointestinal tract and peripheral circulation failure,improving the function of gastrointestinal in patients with MODS.4.The rats model of MODS induced by injecting the belly cavity with the mix liquid of zymosan-paraffin were successful,and matched the diagnostic criteria of MODS animal model.5.It was shown that NF-κB,NO and NOS distributed differently in serum,intestine and heart.The gastrointestinal tract may be the starting fator of the developing of MODS as well as the function of more distant organ beyond gastrointestinal tract was injured from circulation by SIRS,free radical ions and so on. 6.It proved that Jiawei Huanglian Jiedu Decoction had effects on protecting organ function and structure in rats with MODS,its mechanism may be reducing the expression of NF-κB,then to lessen the excess activation of mediators of imflammation and iNOS.7.The depressive effects of NO and NOS are complicated,depressing different isozymes generates different physiology and pathology function,it can protect or injure the organs.