| Research BackgroundSepsis is the systemic inflammatory response syndrome caused by infection,which can be further developed into septic shock and multiple organ dysfunction syndrome.Sepsis is one of the major causes of death in critically ill patients.In the process of sepsis,removing bacteria and producing inflammatory mediators of liver can produce effective defense for the body,but liver will also become a potential target organ attacked by uncontrolled inflammation response.Historically,liver injury happened in the end-stage of sepsis,mainly with clinical manifestation of elevated transaminase and jaundice.But many studies now show liver dysfunction appeared in the early stage of sepsis.Although sepsis is not often associated with liver damage,the condition has reached a critical stage when liver injury is initiated.Therefore,early detection and early treatment of liver injury is important for the prevention and treatment of sepsis.Objective1)To investigate the distribution of main traditional Chinese medicine(TCM)syndromes in sepsis patients with liver injury.2)To use Xijiaodihuang Decoction in the treatment of sepsis in patients with liver injury,to assess efficacy and influence on prognosis.3)Animal models were made by cecal ligation and puncture in rats,and to explore the mechanism of Xijiaodihuang Decoction on liver injury of sepsis.4)To provide a reliable basis for the future clinical development of large-scale multi center prospective study.Method1)To retrieve relevant literatures about sepsis with liver injury and Xijiaodihuang decoction in order toprovide a theoretical basis for the application of Xijiaodihuang Decoction in the treatment of sepsis with liver injury.2)To collected liver parameters and TCM syndromes in two hundreds sepsis patients with liver injury.To use the method of cluster analysis to evaluate symptoms and signs,combined with the theory of wei qi ying xue,and to sum up the classifications of TCM syndrome.To evaluate the relation between the classifications of TCM syndrome and the severity of the disease through the analysis of various categories of patients the index of liver function and prognosis.3)To observe the curative effect of Xijiaodihuang Decoction in the treatment of thirty sepsis patients with liver injury in 3rd,7th day after treatment.The observing indexes are including liver function parameters,APACHE II score,SOFA score and the cumulative survival rate of 28 days.4)The rat model of sepsis was made by cecal ligation and puncture(CLP),and the pathological picture was used as the standard for evaluating liver injury.Experimental group(CLP+XJDHT group)of rats was pre-feeded Xijiaodihuang Decoction,while the control group was normal rats(CLP group).To observe the general conditon,liver function parameters of serum,oxidative stress index of liver,various concentrations of inflammatory factors of serum and STAT1 and STAT3 signal pathway of liver in both groups at 6h,12h,24h.Result1)Through the literature research we found that the treatmeng of sepsis can be treated on base of the theory of wei qi ying xue syndrome.Sepsis patients with liver injury are often in Xuefen syndrome,and are suitable for the use of Xijiaodihuang decoction.2)A total of 200 cases of hepatic injury in septic patients were collected,and three kinds of syndromes were obtained by cluster analysis.After experts' consensus,there were 106 patients with Xuefen syndrome,and 64 patients with Yingfen syndrome,and there were 30 patients with Wei syndrome/Qi syndrome.The liver function parameters and cumulative survival rate of 28 days were analyzed in three groups.The levels of AST,ALT and TBIL in patients with Xue syndrome were higher than those of Wei syndrome/Qi syndrome and Yingfen syndrome(P<0.05).The cumulative survival rate of patients with Xuefen syndrome in 28 days was significantly lower than that of Wei syndrome/Qi syndrome(P<0.01).3)60 cases of sepsis patients with liver injury were randomly divided into Xijiaodihuang Decoction group and control group.After treatment of Xijiaodihuang decoction,ALT,AST and TBIL level were decreased(P<0.05).The APACHE II score and the SOFA score were decreased too(P<0.05).But the 28 day survival rate had no difference in two groups.5)The rat model of sepsis was induced by cecal ligation and puncture,and the model of liver injury was successfully evaluated by pathological pictures.The survival rates of CLP group on 6h,12h and 24h after CLP were 81.25%,45.83%and 37.50%,respectively,while the corresponding survival rates in CLP+XJDHT group were 87.50%,54.16%and 43.75%,respectively.There was no statistical difference between the two groups.6)The level of serum ALT and AST in CLP+XJDHT group was significantly lower than that in CLP group at 24h(P<0.01),but there was no statistical difference in the level of TBIL.7)The SOD activity in liver of rats in group CLP+XJDHT was higher than that in group CLP on 12h(P<0.05),and the SOD activity in group CLP+XJDHT was higher than that in group CLP on 24h(P<0.01).The MDA level in CLP+XJDHT group was significantly lower than that in CLP group on 12h(P<0.01).The iNOS level in CLP+XJDHT group was significantly lower than that in group CLP on 24h(P<0.01).7)After modeling,the concentration of TNF-?,IL-1? IL-6 and IL-8 in CLP group reached the peak at 6h,and then gradually declined.The concentration of IL-1? in CLP+XJDHT group reached the peak at 6h,while the peak of TNF-?,IL-6 and IL-8 appeared around 12h.The concentration of TNF-?,IL-1?,IL-8 in CLP+XJDHT group were lower than those in the CLP group at 12h(P<0.05).The concentration of IL-6 and IL-8 in CLP+XJDHT group were higher than those in the CLP group at 24h(P<0.05).The peak concentration of IL-4 and IL-10 both appeared at 24h in two groups.The concentration of IL-4 and IL-10 in CLP+XJDHT group were lower than those in CLP group at 6h(P<0.05 or P<0.01).The concentratin of IL-4 and IL-10 levels in CLP+XJDHT group were higher than those in group CLP at 12h and 24h(P<0.01).8)There was no difference in the expression of STAT1mRNA and STAT3 mRNA in the liver tissues between the two groups.There were no differences in protein expression of STAT1 and STAT3 in two groupss.It was found that the level of p-STATl in CLP group was significantly higher than that in CLP+XJDHT group at 6h,12h,24h(P<0.01),and the level of p-STAT3 in CLP group was higher than that in group CLP+XJDHT at 6h,12h(P<0.05).Conclusion1)Cluster analysis of TCM syndromes suggests that sepsis patients with liver injury are suitable for the treatment on syndrome differentiation of Wei Qi Ying Xue theory,and the majority of them are Xuefen syndrome,and the condition of Xuefen syndrome is the most critical.2)The level of alanine aminotransferase and aspartate aminotransferase are sensitive indexes in estimating liver injury,the level of total bilirubin changes later.3)Xijiaodihuang decoction can improve the liver function,critical illness scores of sepsis patients with liver injury,but can not improve the prognosis.4)Xijiaodihuang decoction can improve parts of the liver function parameters in sepsis rats with liver injury.5)The clinical and experimental results show that the level of total bilirubin does not changes obviously in early stage of sepsis,so it is not suitable for the early diagnosis of hepatic injury due to sepsis.6)The mechanism of Xijiaodihuang Decoction improving liver injury may including:reducing oxidative stress and improving antioxidant capacity,decreasing proinflammatory cytokine and increasing inflammatory cytokine release for mediating uncontrolled inflammatory state,and interfering with signaling pathway of STAT1 and STAT3 in early stage of sepsis. |
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