Relationship between coagulation factor VII and progressive hemorrhage of brain contusion in mice

Abstract

Objective To study the correlation between the coagulation factor Ⅶ (FⅦ) and progressive hemorrhage after brain contusion in mice and provide the experimental evidence for the clinical application of recombinant human FⅦa. Methods Twelve male BALB/c mice were given liposome-encapsulated FⅦsiRNA via tail vein at doses of 1, 3, 5 and 10 mg/kg with 3 mice per dosage. The other 3 mice received equivalent volume of normal saline as controls. Two days after the injection, mice blood sampling was used to detect FⅦ mRNA expression in liver using real-time PCR, level of plasma FⅦ using ELISA method, and activity of plasma FⅦ using chromogenic substrate assay. The optimal dose at which FⅦ expression was inhibited was determined. Thirty BALB/c male mice were assigned to two groups (n=15 per group) according to the random number table: FⅦ-suppressing group, mice were injected with FⅦsiRNA at the optimal dose and control group, mice were injected with same volume of negative control vector. The model of brain contusion was established in both groups. Volume of hemorrhage following brain contusion was measured at 3, 24 and 72 h postinjury, and hematoma volume at 24 and 48 h postinjury. Results Liposome-encapsulated siRNA delivery down-regulated FⅦ expression in the mouse liver. Level and activity of plasma FⅦ were also reduced significantly. The optimal siRNA dose was 3 mg/kg. At 3, 24 and 72 h postinjury, relative volume of brain hemorrhage in FⅦ-suppressing group was 1.46±0.10, 1.82±0.23 and 2.28±0.15 respectively, significantly higher than that in control group(1.00±0.25, 1.20±0.31 and 1.20±0.22 respectively)(P<0.05). At 24 and 48 h postinjury, volume of hematoma in FⅦ-suppressing group was (6.7±1.5)mm3 and (9.8±1.0)mm3, significantly higher than that in control group [(5.2±1.2)mm3 and (5.5±1.5)mm3](P<0.01). Conclusions Level of FⅦ in vivo relates closely to the progressive hemorrhage of brain contusion in mice. Administration of FⅦ is effective to reduce the incidence of progressive hemorrhage. Key words: Factor Ⅶ; Brain injuries; Cerebral hemorrhage