摘要
Recent studies have showed that thrombosis is closely related to leucocytes involved in immunity.Interfering with the binding of leukocyte integrin Mac-1 and platelet GPIbαcan inhibit thrombosis without affecting physiological coagulation.Mac-1-GPIbαis proposed as a potential safety target for antithrombotic agents.Guanxinning tablet(GXNT)is an oral Chinese patent medicine used for the treatment of angina pectoris,which contains phenolic acid active ingredients,such as salvianolic acids,ferulic acid,chlorogenic acid,caffeic acid,rosmarinic acid,tanshinol,and protocatechualdehyde.Our previous studies demonstrated that GXN exhibited significant antithrombotic effects,and clinical studies suggested that it did not increase bleeding risk.In addition,GXN exerted a significantly regulatory effect on immune inflammation.In the current study,we intended to evaluate the effects of GXN on bleeding events and explore the safety antithrombotic mechanism of GXN based on leukocyte-platelet interaction.First,we established a gastric ulcer model induced by acetic acid in rats and found that GXN not only did not increase the degree of gastrointestinal bleeding when gastric ulcer occurred,but also had a certain promoting effect on the healing of gastric ulcer.Second,in vitroexperiments showed that after pretreatment with GXN and activation by phorbol 12-myristate-13-acetate(PMA),the adhesion and aggregation of leukocytes with human platelets were reduced.It was also found that GXN reduced the expression and activation of Mac-1 in leucocytes,and inhibited platelet activation due to leukocyte engagement via Mac-1.Overall,the results suggest that GXN may be a safe antithrombotic agent,and its low bleeding risk mechanism is probably related to inhibited leukocyte-platelet aggregation and its interaction target Mac-1-GPIbα.
