Thrombocytopenia induced by lipopolysaccharide may be not related to coagulation and inflammatory response / 中华危重病急救医学

ABSTRACT

ObjectiveTo explore the relationship between thrombocytopenia (TCP) induced by lipopolysaccharide (LPS) and coagulation or inflammatory response in mouse.Methods Forty-eight C57BL/6 mice were divided into control group, low-dose, and high-dose LPS treatment groups by random number table method, and each group was subdivided into 4-hour and 24-hour subgroups randomly, with 8 mice in each subgroup. 0.5 mg/kg or 50 mg/kg LPS was injected intraperitoneally in low-dose or high-does group respectively, and equal amount of normal saline was injected in control group. Blood was collected from endocanthal vein at the specified time point, platelet count (PLT) was counted, and the levels of thrombin antithrombin complex (TAT), D-dimer, fibrinogen degradation product (FDP), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were determined by enzyme linked immunosorbent assay (ELISA).Results Compared with control group, PLT (×109/L) at 4 hours and 24 hours in low-dose and high-dose LPS groups was significantly decreased (4 hours 660.65±180.48, 568.55±117.99 vs. 1 199.13±110.54; 24 hours505.63±218.92, 256.33±72.86 vs. 1 229.13±1 189.37, allP< 0.05), and the changes were more obvious in high-dose LPS group compared with those of the low-dose LPS group (allP< 0.05). Factorial analysis showed that the changes in PLT were related with LPS dosage and time (F1 = 135.660,P1 = 0.000;F2 = 12.120,P2 = 0.001). It was also found that there was an interactive effect of the dose of LPS and time on PLT (F = 5.580,P = 0.007). Compared with control group, TAT, TNF-α, and IL-6 at 4 hours and 24 hours in low-dose and high-dose LPS groups were significantly decreased [TAT (ng/L) at 4 hours 1.10±0.59, 0.22±0.13 vs. 3.47±1.73; 24 hours 1.18±0.68, 0.39±0.29 vs. 3.19±1.27;TNF-α (nmol/L) at 4 hours 87.35±12.29, 93.70±5.25 vs. 101.59±10.96, 24 hours 81.94±8.26, 93.23±4.71 vs. 102.84±10.56; IL-6 (ng/L) at 4 hours 81.78±7.82, 78.59±9.06 vs. 110.88±9.66, 24 hours 76.03±9.85, 71.34±3.69 vs. 110.88±10.35, allP< 0.05]. TAT at 4 hours and 24 hours in high-dose LPS group was further decreased, and TNF-αat 24 hours was increased as compared with those of low-dose LPS group (allP< 0.05). TAT, TNF-α and IL-6 were influenced only by different dosage of LPS (TATF = 42.350,P = 0.000; TNF-αF = 14.810,P = 0.000; IL-6F =81.910,P = 0.000), not time (TATF = 0.002,P = 0.967; TNF-αF = 0.342,P = 0.562; IL-6F = 2.973,P = 0.092). Changes in TAT was not found to be related with the dose of LPS and its time of action, or levels of TNF-α and IL-6 (TATF = 0.236,P = 0.791; TNF-αF = 0.572,P = 0.569; IL-6F = 0.774,P = 0.468). The dosage of LPS and time of admission showed no influence on D-dimer (F1 = 2.448,P1 = 0.099;F2 = 0.024,P2 = 0.877). The effect of different doses of LPS and time of administration showed no influence on FDP (F1 = 0.106,P1 = 0.900;F2 = 0.013,P2 = 0.908), and no interactive effects were found (D- dimerF = 0.002,P = 0.998; FDPF = 0.582,P = 0.563).Conclusion LPS can induce TCP in mouse, but this effect may not related to the activation of coagulation system and excessive inflammatory response.