Effect of recombinant human thrombopoietin on platelet activation and pyroptosis in mice with thrombocytopenia / 中华急诊医学杂志

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 groupsblank 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＜ 0.01).Compared with the LPS group,the survival rates of the L,M and H groups were slightly increased,but the difference was not statistically significant (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 signiftcantly higher than those in the LPS,M and H groups (P＜0.01),and there was no significant difference between the M and H groups and LPS group (P＞0.05).Compared with the sham group,CD61/CD62p and Gasdermin-D protein expressions in the LPS group were significantly increased (P＜0.01),significantly decreased in the L group (P＜0.05),and not significantly changed in the M and H groups (P＞0.05).Caspase-1 expression was significantly increased in the LPS group compared with the sham group (P＜0.01),significantly decreased in the L and M groups compared with the LPS group (P＜0.05),and not significantly changed in the H group compared with the LPS group (P＞0.05).The levels ofplatelet-rich plasma IL-1 beta and IL-18 in the LPS group were significantly higher than those in the sham group (P＜0.01),while those in the L group were significantly lower than those in the LPS group (P＜0.01),and those in the M and H groups were not significantly changed than those in the LPS 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.