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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。
Objective To investigate the effect and mechanism of 4-phenylbutyrate (PBA) on cerebral edema after intracerebral hemorrhage (ICH) in rats. Methods Healthy male SD rats were randomly divided into ICH group, PBA 100 mg · kg -1 group, PBA 300 mg · kg -1 group (n = 15) and sham operation group (n = 9) The ICH model was established by stereotactic injection. The PBA intervention group at different dosage groups were intraperitoneally injected with corresponding dose of PBA every 24 h after operation, and the neurological function scores of rats in each group were evaluated at different time points after operation. The rats in each group were sacrificed at 72 hours after operation, the cerebral edema was detected by wet and dry method, the permeability of blood-brain barrier was detected by Evans blue method, and the expression of matrix metalloproteinase 9 (MMP) -9) expression changes. Results The neurological deficit in PBA 300 mg · kg -1 group was significantly lower than that in ICH group at each time point (P <0.05). At 72 h after ICH, the brain water content and Evans blue content in PBA 100 mg · kg-1 group and PBA 300 mg · kg-1 group were significantly lower than those in ICH group (P <0.05); The expression of MMP-9 Also significantly lower than ICH group (P <0.05). Conclusion PBA can improve neurological deficit in rat ICH model, reduce edema after ICH, improve permeability of blood-brain barrier and inhibit the expression of MMP-9 in perihematomal brain tissue.