Effect of recombinant human thrombopoietin on platelet activation and pyroptosis in mice with thrombocytopenia

Abstract

Objective To study the effect and mechanism of recombinant human thrombopoietin (rhTPO) on platelet activation and pyroptosis in mice with lipopolysaccharide (LPS)- induced thrombocytopenia, and provide a theoretical basis for the clinical use of rhTPO. Methods One hundred C57BL/6 mice were randomly(random number) divided into 5 groups: blank control group (sham group), experimental control group (LPS group), low dose (L group, 1.35 ×103U·kg-1·d-1), medium dose (M group, 2.7 ×103U·kg-1·d-1), and high dose (H group, 5.4 ×103U·kg-1·d-1) rhTPO treatment groups. Continuous observation for 72 h. The positive expression rates of CD61/CD62p, Gasdermin D and Caspase-1 in washed platelets were detected by flow cytometry at 72 h, and the levels of IL-1β and IL-18 in plasma were detected by ELISA. Results Compared with the sham group, the survival rate of the LPS group was significantly lower (P 0.05). There was no significant change in platelet count of the sham group before and after the experiment. The platelet count in the LPS group decreased significantly. The platelet count at 72 h in the L group was significantly higher than those in the LPS, M and H groups (P 0.05). Compared with the sham group, CD61/CD62p and Gasdermin-D protein expressions in the LPS group were significantly increased (P 0.05). Caspase-1 expression was significantly increased in the LPS group compared with the sham group (P 0.05). The levels of platelet-rich plasma IL-1 beta and IL-18 in the LPS group were significantly higher than those in the sham group (P 0.05). Conclusions rhTPO can inhibit platelet activation and pyroptosis in LPS-induced thrombocytopenia mice, which provides basic research basis for the treatment of sepsis thrombocytopenia. Key words: Recombinant human thrombopoietin; Thrombocytopenia; Platelet activation; Pyroptosis; Lipopolysaccharide