Expression Of Platelet Surface Receptor CD62P In Septic Rats And The Cardioprotective Effect Of Ticagrelor

Objective: To observe the expression of platelet surface receptor CD62 P,inflammatory factors and myocardial injury in septic rats,and to investigate the anti-inflammatory effect of ticagrelor and the protective effect of ticagrelor on myocardial injury in septic rats.Methods: Thirty-two specific pathogen-free SD male rats,6-8 weeks old,weighing220-320 g,were used.The rats were randomly divided into 4 groups: Sham operation group(Sham),sepsis group(CLP),low dose group(10mg/kg)and high dose group(50mg/kg),with 8 rats in each group.The rats in the sham operation group were only treated with abdominal opening and cecal dissection,and the rats in the sepsis group,the low-dose administration group,and the high-dose administration group were treated with cecal ligation and puncture(CLP)to establish the sepsis rat model.Ticagrelor(10mg/kg and 50mg/kg)was administered by gavage in the administration group,and normal saline(1ml/kg)was administered by gavage in the sham operation group and the sepsis group.The rats were administrated twice by gavage 12 hours before and 12 hours after surgery.Blood samples were collected from the abdominal aorta 24 hours after modeling and pathological specimens were collected.The expression of platelet surface receptor CD62 P was detected by flow cytometry.The levels of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)were detected by enzyme-linked immunosorbent assay(ELISA).Biochemical analyzer was used to detect myocardial injury markers: Creatine Kinase-MB(CKMB),lactate dehydrogenase(LDH),liver and kidney function: The changes of ALanine aminotransferase(ALT)and creatinine(CR)were detected,and the white blood cell count(WBC)was detected by whole blood cell analyzer.hematoxylin-eosin staining was used for myocardial tissue.HE staining was used to observe the pathological morphology and Td T-mediated d UTP-biotin nick end labeling(TUNEL)was used to observe cardiomyocyte apoptosis.Results:1.Platelet activation: Flow cytometry was used to detect the expression of platelet surface receptor CD62 P in rats.The results showed that compared with the sham operation group,CLP could significantly increase the expression of platelet CD62P(P<0.0001),ticagrelor significantly reduced platelet CD62 p expression(P<0.05),and the expression of CD62 P decreased more significantly in the high-dose group.2.The changes of inflammatory factors interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α): the levels of TNF-α and IL-6 in the CLP group were significantly increased(p<0.05),and the level of IL-6 was increased more significantly.Ticagrelor dose-dependently reduced the level of IL-6 in the septic rats(P<0.05).However,ticagrelor intervention had no significant effect on TNF-α level.3.Changes of myocardial injury markers: the changes of CKMB and LDH in serum of rats were detected by biochemical analyzer.The levels of CKMB and LDH in rats after CLP were significantly higher than those in the control group(p<0.0001),and the myocardial injury markers in the drug group were significantly lower than those in the sepsis group(p<0.05),and showed a dose-dependent manner.4.Changes of liver and kidney function and white blood cell: compared with the sham operation group,the levels of alanine aminotransferase(ALT),creatinine(CR)and white blood cell(WBC)in the sepsis group were significantly increased(p<0.0001);At the same time,the liver and kidney function and hemogram of the administration group were significantly improved than those of the CLP group(p<0.05),and the high-dose group was more significant.5.Pathological changes of myocardial tissue: HE staining of myocardial tissue of rats in each group showed that compared with the sham operation group,the myocardial fibers in the sepsis group were relatively irregular,lost their normal shape,the structure of myocardial tissue was loose,the fibers were broken,the inflammatory cell infiltration increased,and the formation of fiber vacuoles.Compared with the sepsis group,the damage of myocardial cells in the ticagrelor administration group was significantly reduced.The structure of myocardial fibers in the ticagrelor administration group was relatively normal,with no obvious tissue necrosis and vacuoles,but there were still some myocardial fibers rupture.There were no significant changes in the morphology and nucleus of cardiomyocytes in the low-dose group compared with the high-dose group.6.Myocardial cell apoptosis: TUNEL staining results confirmed that the apoptosis of myocardial cells in the sepsis group was significantly higher than that in the sham operation group.At the same time,the number of apoptotic cardiomyocytes in the low-dose ticagrelor group and the high-dose ticagrelor group was significantly lower than that in the sepsis group.Conclusions: Sepsis can activate platelets by stimulating the expression of CD62 P,thereby inducing excessive activation of inflammatory response,causing apoptosis and damage of cardiomyocytes,and leading to sepsis-related myocardial dysfunction.The cardioprotective effect of ticagrelor may be related to the inhibition of the reduction of CD62 p expression after platelet activation,and the expression level of CD62 p has a dose-dependent relationship with ticagrelor.