Effects Of Antiplatelet Drugs On Liver Injury Induced By Sepsis

Object: The effects of ticagrelor and aspirin on inflammation and liver injury in sepsis mice are observed to explore the possible mechanisms and find new approaches for the treatment of sepsis.Methods: The 96 healthy male C57 bl / 6 mice were selected into two groups at random,which were named the A group and the B group respectively.Each group was randomly divided into the control group?LPS group,LPS+aspirin group?LPS+ticagrelor group,with 12 mice.The Control group and LPS group were given 0.2ml of pure water,and the LPS+aspirin group was given 100mg/kg of aspirin and 0.2ml of pure water,and the LPS+ticagrelor group was given 100mg/kg and 0.2ml of pure water.One hour later after being gavaged,the mice in control group was injected with 0.1ml of physiological saline,while mice in the LPS group,LPS+aspirin group and LPS+ticagrelor group were given respectively LPS(sigmaO55:B5)30mg/kg to the intraperitoneal injection dissolution in 0.1ml physiological saline.A group was arcotized at 12 h after the model.The blood and the liver tissues of mice were collected,and the serum Il-6,TNF-?,CD62 P and Histone4 were detected by Elisa,and the ALT content in serum was detected by blood biochemical method.PCR method was used to detect the expression level of TNF-a and IL-6 in liver tissues.Westernblot method was used to detect fibrinogen deposition in the liver and HE staining to observe the degree of liver tissue pathological changes under the light microscope.In the B group,the results were observed at the same time every 24 hours,and the survival state was observed every 2h,and after 96 h we can describe the survival curve.Results: 1.Basic situation: the control group has a good mental state,the drinking water intake is normal,breathing is stable,and the stimulation reaction is sensitive.The mice in LPS group had fast breathing,standing hair,listlessness and less movement and were lack of diet.The purulent secretions were presented in the eyes and stimulation response were poor.The LPS+aspirin group had symptoms above,but was less than the LPS group.The LPS+ticagrelor group had the above poisoning symptoms and was less than the LPS group.After intraperitoneal injection of LPS for 12 h,no deaths occurred in each group.2.Serum ALT concentration: compared with the control group,the serum ALT of LPS group was significantly increased,and the ALT value of LPS+aspirin group and LPS+ticagrelor group was higher than the control group,but all were lower than the LPS group.(p < 0.05)3.Serum IL-6,TNF-? and Histone4: compared with the Control group,the serum IL-6,TNF-? and Histone4 were significantly increased in the LPS group,while the LPS+aspirin group and the LPS+ticagrelor group were less compared with the LPS group.4.Serum CD62P: after intraperitoneal injection of LPS,CD62 P in each group increased,and it was the highest in LPS group,and lower in LPS+aspirin group,LPS+ticagrelor group(P<0.05).5.Expression of IL-6 and TNF-? of liver tissue: it was lower in LPS+ticagrelor group compared with LPS group.The expression of LPS+aspirin group rose,which was higher than that of LPS group.(P>0.05)6.Fibrinogen in liver tissue deposition: The liver tissue deposition of Fibrinogen significantly increased in LPS group and control group.While LPS + aspirin group and LPS + ticagelor comparing with LPS group sedimentary reduced(P<0.05).the results in LPS+ aspirin group and LPS + ticagrelor group had no obvious differences.(P>0.05)7.Pathological changes of liver tissue HE staining: The Control group was normal liver tissue structure with no cell edema necrosis.The liver cells of LPS group were widely edema,and the liver cells showed patchy necrosis,the liver plate and the liver sinus were disordered,and the inflammatory cells were infiltrated.The liver cells of the LPS+aspirin group were widely edema,the cytoplasm was bright,the hepatic sinus was narrowed or disappeared,and the liver cells showed focal necrosis with inflammatory cell infiltration.Liver cell edema in LPS+ticagrelor group was slightly reduced compared with that in aspirin group,and it was found that liver cells were necrotic,focal necrosis,a little inflammatory cell infiltration,and liver tissue structure was complete.8.Survival rate: the 96 h survival rate of the LPS+aspirin group and the LPS+ticagrelor group was higher than that in the LPS group.Conclusion: LPS can enhance platelet activation in sepsis,and aspirin and ticagrelor can reduce the inflammatory response of sepsis and relieve the degree of liver damage in mice.The mechanism may be related to antiplatelet agents to inhibit platelet activation of sepsis,which can inhibit over-acting inflammatory and coagulation caused by excessive activation of platelets.