Effect of basic fibroblast growth factor on reducing intracranial pressure in rats after abdominal hypertension / 中华创伤杂志

ABSTRACT

Objective:To investigate the role of basic fibroblast growth factor (bFGF) in decreasing intracranial pressure in rats after intra-abdominal hypertension (IAH).Methods:A total of 60 healthy SD rats were selected for the experiment. Secondary IAH rat models were established by hemorrhagic shock/resuscitation, followed by injecting nitrogen into the peritoneal cavity of the rats to maintain an intra-abdominal pressure of 12mmHg and above. According to the random number table, the rats were divided into control group, IAH group, IAH+ bFGF group (bFGF group) and IAH+ bFGF+ PD173074 group (antagonist group), with 15 rats per group. Indicators were measured 4 hours after injury, including intracranial pressure, brain morphological observation, apparent diffusion coefficient (ADC) value, lactic acid content of brain MRI, brain water content and Evans blue exudation. Immunofluorescence staining, Western blotting and PCR were used to detect the expressions of phosphorylate-fibroblast growth factor receptor 1, 2 (p-FGFR1, 2), Zonula occludens-1 (ZO-1), β-catenin, matrix metalloproteinases 9 (MMP9), interleukin-1β (IL-1β) in brain microvascular endothelial cells (BMECs).Results:The intracranial pressure in IAH group [(5.52±0.45)mmHg] gradually increased 4 hours after injury compared control group [(3.36±0.30)mmHg]. Compared with IAH group, the intracranial pressurein bFGF group [(4.46±0.41)mmHg] was decreased ( P<0.05). Compared with bFGF group, the intracranial pressure in antagonist group [(5.36±0.44)mmHg] was enhanced ( P<0.05). Brain morphological observations in IAH group showed swelling and obvious cerebral edema, accompanied with a small amount of subarachnoid hemorrhage. Compared with IAH group, cerebral edema and brain swelling were relieved in bFGF group, while the antagonist group still showed cerebral edema and obvious brain swelling. At 4 hours after injury, MRI examination showed that the relative ADC value in IAH group (cortex 0.82±0.11, corpus callosum 1.26±0.17) was lower than that in control group (cortex 1.00±0.13, corpus callosum 1.43±0.15)( P<0.05). Compared with IAH group, the relative ADC value in bFGF group (cortex 0.94±0.16, corpus callosum 1.36±0.16) was increased ( P<0.05). Compared with bFGF group, the relative ADC value in antagonist group (cortex 0.87±0.13, corpus callosum 1.30±0.14) was decreased ( P<0.05). Relative lactic acid content in IAH group (cortex 15.50±2.14, corpus callosum 10.82±1.90)was higher than that in control group (cortex 1.00±0.23, corpus callosum 0.70±0.20)( P<0.05). Compared with IAH group, the relative lactic acid content in bFGF group (cortex 10.85±1.42, corpus callosum 6.96±1.30) was decreased ( P<0.05). Compared withbFGF group, the relative lactic acid content in antagonist group (cortex 13.71±1.61, corpus callosum 9.12±1.52) was increased ( P<0.05). The brain water content in IAH group [(87.9±0.8)%] was higher than that in control group [(76.3±0.9)%]. Compared with IAH group, the brain water content in bFGF group [(83.2±1.0)%] was decreased( P<0.05). Compared with bFGF group, the brain water content in antagonist group[(85.4±0.8)%] was increased ( P<0.05). Evans blue exudation in IAH group [(3.22±0.29)μg/ml] was greater than that in control group [(0.42±0.22)μg/ml]( P<0.05). Compared with IAH group, the Evans blue exudation in bFGF group [(2.04±0.25)μg/ml] was decreased ( P<0.05). Compared with bFGF group, the Evans blue exudation in antagonist group [(2.92±0.20)μg/ml] was increased ( P<0.05). Compared with control group, the expression of p-FGFR1 in BMECs in IAH group was weakened 4 hours after injury, but p-FGFR2 remained unchanged, the expressions of ZO-1, β-catenin protein and mRNA were weakened, and the expressions of MMP9, IL-1β protein and mRNA were enhanced ( P<0.05). Compared with IAH group, the expressions of p-FGFR1, ZO-1, β-catenin protein and mRNA were enhancedin bFGF group, and the expressions of MMP9, IL-1β protein and mRNA were weakened as well ( P<0.05). However, the expressions of p-FGFR1, ZO-1 and β-catenin protein and mRNA in antagonist group were weaker than those in bFGF group, and the expressions of MMP9 and IL-1β protein and mRNA were stronger than those in the bFGF group ( P<0.05). Conclusion:After IAH, the rat model presents damaged blood-brain barrier, increased cerebral edema, and increased intracranial pressure, and the use of bFGF can improve these symptoms. FGFR1 of BMECs is a key receptor for bFGF to play a protective role, and its receptor inhibitor PD173074 can attenuate the protective effect of bFGF.