Study On The Protective Effect Of Rhubarb On Vascular Endothelial Cells Function In Sepsis

Part I Experimental study on the protective effect of emodin on vascular endothelial cell function in septic ratsObjective:To detect the effect of emodin on the function of vascular endothelial cells after the cecal ligation and puncture(CLP)in septic rats.Methods: Fifty-four SPF Sprague Dawley rats were randomly split into three groups:the normal control group(n=18),the CLP group(1ml/100 g normal saline immediately after CLP)(n=18)and the emodin group(1ml/100 g emodin solution immediately after CLP)(n=18).Coagulation items were detected including prothrombin time(PT),fibrinogen and activated partial thromboplastin time(APTT),D-dimer,fibrinogen degradation products(FDP),platelet count,plasma TM,PAI-1and v WF.Results:Compared with normal control group,the TM of CLP group increased rapidly at6 h after surgery and reached a peak,showing a slow decline at 12 h and 24 h,but still higher than that of the normal control group(P<0.05);the D-dimer and v WF levels in the CLP group began to increase significantly at 6 h postoperatively and reached a peak at 24 h postoperatively(P<0.05);the fibrinogen level in the CLP group began to rise at 12 h postoperatively and was significantly higher at 24 h(P<0.05);the platelet count in the CLP group continued to decrease at 6h postoperatively and peaked at 24 h postoperatively(P <0.05);the level of PAI-1 was significantly increased at 24 hours after CLP(P>0.05);The APTT of CLP group was significantly prolonged 24 h after surgery(P<0.05).Compared with the CLP group,the TM level of the emodin group decreased significantly at 6h postoperatively(P<0.05),the TM level in the emodin group decreased significantly at 12 h and 24 h postoperatively,but the difference was not statistically significant(P>0.05);the D-dimer level in the emodin group decreased significantly at 6 h and 24 h postoperatively(P<0.05);the v WF level in the emodin group decreased significantly at 6 h,12 h and 24 h postoperatively(P<0.05);and the platelet count in the emodin group was significantly increased at 12 h and 24 h postoperatively(P <0.05);There was no significant differences in PT and FDP levels in the emodin group at 6 h,12 h and 24 h postoperatively(P>0.05).Conclusion : Endothelial damage occurred after CLP in septic rats,and mainly manifested in the significant increase of TM,v WF and PAI-1.Emodin can down-regulate the levels of TM and v WF in septic rats,which has protective effect on vascular endothelial cells.Part II Clinical study on the protective effect of rhubarb on vascular endothelial function in sepsis patientObjective To evaluate the protective effect of rhubarb on vascular endothelial cells function in patients with sepsis by endothelial molecular markers.Methods we carried out a prospective,single-center,randomized controlled study based on 41 patients with sepsis who admitted to the Intensive Care Unit of the 908 th Hospital of PLA.Patients were randomly split into the rhubarb treatment group(n=20)and the control group(n=21).Blood samples were collected before,24 h and 72 h after the medication.Conventional coagulation tests[ PT,APTT,fibrinogen,thrombin time(TT),FDP,D-dimer,antithrombin(AT-Ⅲ),platelet count,platelet distribution width] and coagulation molecular markers including TM,tissue plasminogen activator-inhibitor complex(t-PAIC),antithrombin complex(TAT),plasmin-α2anti-plasmin complex(PIC)were detected and statistically analyzed.Results The fibrinogen level [(3.5±1.0)g/L] at the 72 h after administration in the rhubarb treatment group was significantly higher than that of the control group[(2.7±0.8)g/L] and the rhubarb treatment group before administration[(2.7±0.9)g/L](P<0.05).Compared with the serum TM [19.0[(15.5-22.6)TU/ml] and t-PAIC[15.4(9.7-20.9)ng/ml] levels before treatment in the control group,the TM[27.3[(20.8-31.2)TU/ml] and t-PAIC [22.2(15.5-38.6)ng/ml] at the 72 h after administration in the control group significantly increased(P<0.05).Compared with TM and t-PAIC of the control group,the TM [13.2(10.9-18.0)TU/ml] and t-PAIC[9.2(7.3-23.1)ng/ml] at the 72 h after administration in the rhubarb treatment group were significantly decreased(P<0.05).Compared with the serum TM [19.7(17.1-23.4)TU/ml] levels before treatment and the TM [18.6(15.3-21.1)TU/ml] at the 24 h after administration in the rhubarb treatment group,the TM at the 72 h after administration were significantly decreased(P<0.05).Kaplan-Meier analysis revealed that there was no statistically significance in 14-day survival rate between the two groups(P>0.05).Conclusion Chinese rhubarb can down-regulate TM and t-PAIC levels and improve vascular endothelial function in patients with sepsis.