4-苯基丁酸对大鼠脑出血模型脑水肿的作用及机制探讨

Effect and Mechanism of 4-phenylbutyric Acid on Brain Edema in Rat Model of Intracerebral Hemorrhage

目的探讨4-苯基丁酸(PBA)对大鼠脑出血(ICH)后脑水肿的作用及机制。方法健康雄性SD大鼠,随机分为ICH组、PBA 100 mg·kg-1组、PBA 300 mg·kg-1组(均n=15)和假手术组(n=9),采用自体血脑内立体定向注射法建立大鼠ICH模型,不同剂量组PBA干预组于术后即刻每24 h腹腔注射相应剂量的PBA,评价术后不同时间点各组大鼠神经功能评分。各组大鼠均于术后72 h处死,干湿重法检测脑水肿情况,伊文思蓝法检测血脑屏障通透性变化,同时Western blot法检测血肿周围脑组织中基质金属蛋白酶9(MMP-9)表达的变化。结果 PBA 300 mg·kg-1组各时间点神经功能缺损显著低于ICH组(P<0.05)。ICH后72 h,PBA 100 mg·kg-1组、PBA 300 mg·kg-1组脑组织含水量和伊文思蓝含量显著低于ICH组(P<0.05);血肿周围组织中MMP-9表达也显著低于ICH组(P<0.05)。结论 PBA能够改善大鼠ICH模型的神经功能缺损,减轻ICH后水肿和改善血脑屏障通透性,抑制血肿周围脑组织中MMP-9的表达是可能作用机制。

Aim To explore the protective effects and mechanisms of 4-phenylbutyrate（PBA） on brain edema in rat model of intracerebral hemorrhage（ICH）. Methods Male SD rats were randomly divided into four groups： 1 ICH group（n=15）; 2 100 mg·kg-1 PBA intervention group（n=15）; 3 300 mg·kg-1PBA intervention group（n=15）; 4 Sham operation group（n=9）. The ICH model was made by infusing 100 μL autologous blood into caudate nucleus stereotactically. PBA was administrated intraperitoneally every 24 hours. Rats were euthanized at 72 h after being assessed the degree of neurological function damage. The brain water content and permeability of blood brain barrier were detected using wet-dry weight ratio method and the use of the Evans blue respectively, and the expression of MMP9 around the hematoma was measured by Western blot in different groups. Results Neurological deficits in 300 mg·kg-1 PBA intervention group was improved compared with ICH group, which differences were statistically significant（P0.05）. The brain water content and Evans blue content were both lower in PBA intervention group than ICH group at 72 h after ICH. The expression of MMP-9 in brain tissue surrounding hematoma significantly decreased in PBA intervention group（P0.05）. Conclusion PBA can improve neurological deficits, reduce brain edema and blood brain barrier permeability with decrease of the expression of MMP-9 surrounding hematoma in rat model of intracerebral hemorrhage.