RESUMO
Objective • To investigate the effect of Toll-like receptor 4 (TLR4) in the pathological injury in fat embolism mice model. Methods • One hundred and twenty male C57BL/6 mice were randomly divided into 10 groups. One group was set as blank control group, and others were injected separately with 1, 2…9 μL/g of allogeneic perirenal fat via tail vein, respectively. The mortality of each group was counted, median lethal dose (LD50) of fat injection in mice was calculated by Bliss method, and the fat embolism LD50 mice model was established. The TLR4 protein expression in the pulmonary tissue of surviving mice was detected by Western blotting. Sixty male C57BL/6 mice were randomly divided into the control group (the same dose of saline was given via tail vein) and the experimental groups (group 2 h, group 8 h, group 24 h and group 48 h, the LD50 fat was given via tail vein). The TLR4 protein expression at different time after fat injection was detected by Western blotting. The mortality of 20 TLR4 gene-knockout mice (TLR4-/- mice) was recorded and compared with 60 wild-type mice after LD50 fat injection. Results • The LD50 of fat embolism mice model was (3.93±0.78) μL/g. After the injection of 1-7 μL/g fat, the expressions of TLR4 protein in the pulmonary tissue of all seven groups were significantly increased, compared with the control group (all P=0.000). In the fat embolism LD50 mice model, compared with the control group, the expressions of TLR4 protein in group 2 h were significantly increased (P=0.005). Then, expression level of TLR4 protein was gradually reduced after 2 h, and there was no significant difference between the control group and group 48 h. The mortality of TLR4-/- mice injected with LD50 fat was lower than that of wild-type mice (P=0.043). Conclusion • TLR4 protein involves in the pathologic process of fat embolism syndrome. The knockout of TLR4 gene can reduce the mortality of fat embolism mice. TLR4 and its correlated non-infectious inflammatory response may be an important molecular mechanism of biochemical injury in fat embolism syndrome. Blocking the activation of TLR4-mediated signaling pathway can significantly improve the prognosis, which provides new basis for the prevention, evaluation and treatment of fat embolism syndrome.
RESUMO
Objective · To investigate the effect of Toll-like receptor 4 (TLR4) in the pathological injury in fat embolism mice model. Methods · One hundred and twenty male C57BL/6 mice were randomly divided into 10 groups. One group was set as blank control group, and others were injected separately with 1, 2…9 μL/g of allogeneic perirenal fat via tail vein, respectively. The mortality of each group was counted, median lethal dose (LD50) of fat injection in mice was calculated by Bliss method, and the fat embolism LD50 mice model was established. The TLR4 protein expression in the pulmonary tissue of surviving mice was detected by Western blotting. Sixty male C57BL/6 mice were randomly divided into the control group (the same dose of saline was given via tail vein) and the experimental groups (group 2 h, group 8 h, group 24 h and group 48 h, the LD50 fat was given via tail vein).The TLR4 protein expression at different time after fat injection was detected by Western blotting. The mortality of 20 TLR4 gene-knockout mice (TLR4-/-mice) was recorded and compared with 60 wild-type mice after LD50 fat injection. Results · The LD50 of fat embolism mice model was (3.93±0.78) μL/g.After the injection of 1-7 μL/g fat, the expressions of TLR4 protein in the pulmonary tissue of all seven groups were significantly increased, compared with the control group (all P=0.000). In the fat embolism LD50 mice model, compared with the control group, the expressions of TLR4 protein in group2 h were significantly increased (P=0.005). Then, expression level of TLR4 protein was gradually reduced after 2 h, and there was no significant difference between the control group and group 48 h. The mortality of TLR4-/- mice injected with LD50 fat was lower than that of wild-type mice (P=0.043).Conclusion · TLR4 protein involves in the pathologic process of fat embolism syndrome. The knockout of TLR4 gene can reduce the mortality of fat embolism mice. TLR4 and its correlated non-infectious inflammatory response may be an important molecular mechanism of biochemical injury in fat embolism syndrome. Blocking the activation of TLR4-mediated signaling pathway can significantly improve the prognosis, which provides new basis for the prevention, evaluation and treatment of fat embolism syndrome.