Effect of recombinant human thrombopoietin on platelet activation and pyroptosis in mice with thrombocytopenia
10.3760/cma.j.issn.1671-0282.2019.10.019
- VernacularTitle: 重组人血小板生成素对血小板减少症模式小鼠血小板活化及焦亡的影响
- Author:
Jiawei JIANG
1
;
Xin YU
1
;
Hua YU
2
;
Bing WANG
2
;
Yongqing WANG
2
Author Information
1. Tianjin Medical University First Center Clinical College, Tianjin 300192, China
2. Department of Critical Care Medicine, Tianjin First Center Hospital, Tianjin, 300192, China; Tianjin First Center Hospital Emergency Medical Research Institute, Tianjin, 300192, China
- Publication Type:Journal Article
- Keywords:
Recombinant human thrombopoietin;
Thrombocytopenia;
Platelet activation;
Pyroptosis;
Lipopolysaccharide
- From:
Chinese Journal of Emergency Medicine
2019;28(10):1277-1281
- CountryChina
- Language:Chinese
-
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< 0.01). 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 significantly 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 of platelet-rich plasma IL-1 beta and IL-18 in the LPS group were significantly higher than those in the sham group (P<0.01), 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.
