Effect of Р2Y12 receptor inhibition on thrombopoiesis and platelets characteristics in rats bone injury modeling

Abstract

Introduction. Bone tissue injury requires the active involvement of platelets in the reparative regeneration process. P2Y₁₂ receptors are important regulators of platelet function, enabling a rapid response to injury. The antiplatelet drug clopidogrel, which indirectly blocks P2Y₁₂ receptors, is widely used in clinical practice and for studying platelet and megakaryocyte function.

Objectives. To study the effect of P2Y₁₂ receptor blockade on the development of MK, parameters and functional activity of the platelets in experimental bone injury.

Methods. The study was performed on female Wistar rats (n=40), divided into two groups. The experimental group was administered clopidogrel intraperitoneally daily for 7 days before surgery (lower jaw injury modeling) and until withdrawal from the experiment (immediately before surgery, 1, 3 and 7 days after surgery). Control animals were without clopidogrel administration, injury was modeled. Platelet indices, platelet aggregation activity with ADP and stages of megakaryocytic lineage cell development in bone marrow punctures were determined.

Results. Irreversible inhibition of P2Y₁₂ receptors had a significant effect on MK development and platelet parameters both before and after injury modeling. A shift in MC towards mature forms was observed, as well as increase in the circulating platelets count before surgery and its increased consumption in the postoperative period.

Conclusions. Changes in MC development and platelet-related parameters when blocking P2Y₁₂ receptors at bone trauma reflect the body's response to the functional insufficiency of the platelet blood component; this must be taken into account during surgical interventions and injuries.