Effects of Qingwen Baidu decoction on coagulation and multiple organ injury in rat models of sepsis

Background:Sepsis-induced coagulopathy and multiple organ dysfunction syndromes are the leading causes of death in patients with sepsis.Qingwen Baidu decoction(QWBD)can effectively improve the clinical manifestations of sepsis and ease inflammation,but its effects on coagulation functions and multiple organ injuries remain unclear.Methods:100 healthy,male Sprague-Dawley rats were randomly divided into the sham group,the cecal ligation and puncture(CLP)group,the low-dose QWBD group,and the high-dose QWBD group,with 25 rats in each group.The sepsis model was established using CLP.Blood was collected to measure platelet count,serum creatinine(Cr),blood urea nitrogen(BUN),alanine aminotransferase(ALT),and aspartate aminotransferase(AST)levels,as well as coagulation function.The total protein in bronchoalveolar lavage fluid(BALF)was determined in each group of rats.The lung,liver,and kidney tissues were harvested,and statistics were calculated on the wet-to-dry(W/D)weight ratio.Changes in histopathology and thrombin level were evaluated in each group.The remaining ten rats in each group were observed daily to record the number of surviving rats.Such observation was made consecutively for 7 days to calculate survival rates.Results:After model establishment,ALT,AST,Cr,and BUN levels were significantly elevated(P<0.01).The BALF protein content and lung W/D weight ratio were significantly increased(P<0.01).Furthermore,the survival rate of rats was significantly reduced in the CLP group compared with the sham group.After the treatment,rats in the high-dose QWBD group had lower ALT(P<0.05),AST(P<0.01),Cr(P<0.05),BUN(P<0.01)levels,lower BALF protein content(P<0.05)and lower lung W/D weight ratio(P<0.01)than the CLP group.However,rats in the high-dose QWBD group had significantly better pathological changes in the lung,liver,and kidney compared to the sham group.After the treatment,the platelet level in the peripheral blood was elevated(P<0.05)and both activated partial thromboplastin time and prothrombin time were significantly shortened(P<0.01).The fibrinogen level was significantly increased(P<0.01).Finally,thrombin positive expression areas in the lung,liver,and kidney were significantly decreased in the high-dose QWBD group.Conclusion:QWBD can improve coagulation disorders caused by sepsis and has a protective effect on multiple organ injuries in rats.

Anti-Inflammatory Effect of Qingwen Baidu Decoction (清瘟败毒饮) in Sepsis Rats

Objective：To explore the pharmacological anti-inflammatory mechanism of Chinese formula Qingwen Baidu Decoction（清瘟败毒饮,QBD） from the view of holistic biology.Methods：The rats were randomly divided into a normal conrol group,a lipopolysaccharide（LPS） group,the low- and high-dose QBD groups,and a dexamethasone（DXM） group.NR8383 cells were treated with culture fluid containing 6%serum from rats of each group respectively.Inflammatory mediators were detected by reverse transcription polymerase chain reaction（RT-PCR）,Western blotting hybridization,enzyme linked immunosorbent assay（ELISA）,polymerase chain reaction（PCR） gene array and antibody array.Results：It is showed that the levels of interleukin（IL）-1 α,IL-4 and IL-12 were enhanced in the low-dose QBD group;levels of IL-1 α,IL-12 and IL-18 were augmented in the high-dose QBD group,compared with the LPS group after ELISA detection.Western blot showed that IL-1β and tumor necrosis factor（TNF）-α expression of the control group were lower than other groups.IL-1 βlevel of the low-dose and high-dose QBD groups detected by RT-PCR was higher in early stage but lower after24 h than that of the control group（P〈0.01）.Expression of 84 main inflammatory cytokines and receptors was detected by rat inflammatory cytokines and receptors PCR array.Up-regulation genes were 22 in both the LPS group and the low-dose QBD group,among which 16 up-regulating genes were the same.In these 16 genes,the up-regulating amplitude of 9 genes in the low-dose QBD group was less than that in the LPS group,4 were similar to and 3 were more.Twenty-nine main cytokines were inspected by rat cytokine antibody array.Intergroup gray value differences were found in 7 expressed cytokines.The levels of these 7 cytokines in the lowdose QBD group were all lower than those in the the LPS group.Conclusions：QBD has anti-inflammatory effect on sepsis by changing the level of inflammatory mediators.