Regulation Of Heparin On The Serum TNF-α、TF And TFPI And The Effect Of Heparin On Coagulation Function In Sepsis Rats

Objective To observe the effects of low dose of heparin on coagulation function, serum levels oftissue factor, tissue factor pathway inhibitor and tumor necrosis factor-αin theendotoxin-induced sepsis rats. Explore the role of low-dose of heparin on early coagulation andinflammatory response in sepsis rats. The pathological changes of lung tissues were observedunder microscope after HE staining. And provide the laboratory evidence to clinical adjuvanttherapy of sepsis.Methods A total of 40 healthy and male Wistar rats were randomly assigned into 5 groups:normal control group, LPS 2 h group, LPS 6 h group, LPS + heparin 2 h group and LPS +heparin 6 h group. The rats were injected with normal sodium 1ml via caudal vein in controlgroup, with LPS 5 mg/kg via caudal vein to establish sepsis model in LPS 2 h group and LPS 6 hgroup, with LPS 5 mg/kg and heparin 100u/kg in LPS + heparin 2 h group and LPS + heparin 6h group.Observe the general status of rats in each group. Specimens were taken after making model 2 hand 6 h. At different time points, the following examinations were carried out: Coagulationfunction was measured with coagulation analyzer (ACL TOP). Serum levels of tissue factor,tissue factor pathway inhibitor and tumor necrosis factor-αwere determined with Enzyme-linkedimmunosorbent assay (ELISA). The pathological changes of lung tissues were observed undermicroscope after HE staining.Results: Compared with control group, PT and APTT were significantly prolonged in LPS 2 hgroup and LPS 6 h group (P<0.01), and they also were prolonged in LPS + heparin 2 h groupand LPS + heparin 6 h group (P<0.05). Compared with LPS + heparin groups, PT and APTTincreased in LPS groups at 2 h and 6 h, respectively (P<0.05), but PT and APTT were notsignificantly different between LPS+ heparin 2 h group and LPS + heparin 6 h group (P>0.05).Compared the level of serum TF with control group, LPS 2 h group and LPS 6 h group weresignificantly higher (P<0.05), and LPS + heparin 2 h group and LPS + heparin 6 h group werestatistically higher (P<0.05). Compared with LPS 2 h group and LPS 6 h group, the serum TFsignificantly decreased in LPS + heparin 2 h group and LPS + heparin 6 h group (P<0.05).TFPI was higher in all groups than that in control group (P<0.05). Compared with LPS 2 h groupand LPS 6 h group, TFPI increased in LPS + heparin 2 h group and LPS + heparin 6 h group(P<0.05).TNF-αwas increased in LPS groups and LPS + heparin groups than that in control group (P<0.05). Compared with LPS 2 h group and LPS 6 h group, TNF-αdecreased in LPS + heparin2 h group and LPS + heparin 6 h group (P<0.05).Observation of general state: after copy animal models, the control group rats showed breathingevenly and good mental state. LPS groups showed apathetic, chills, respiratory distress andcyanosis. Symptoms were severed in LPS 6 h group than in LPS 2 h group, also performedindifferent to the external stimulation. LPS + heparin group showed significantly decreasedactivity and tachypnoea, but these performances were less than they in LPS groups.Pathological results showed that the structure of lung tissues was clear in control group, and thedamage of lung tissue was less in LPS + heparin 2 h group and LPS + heparin 6 h group thanthat in LPS 2 h group and LPS 6 h group.Conclusion Application of heparin could slow the prolonged of PT, APTT and markedly lowerserum TF level, increased serum TFPI level and decreased serum TNF-αlevel. Heparin couldameliorate the disorder of coagulation in sepsis, slow down the mutually promoted role betweencoagulation and inflammation, and alleviate the occurrence of multiple organ dysfunctionsyndrome. Also heparin had a protective effect on lung injury in sepsis.