垂体腺苷酸环化酶激活肽对局灶性脑缺血大鼠脑水肿的影响

Effect of PACAP38 on brain edema after transient focal ischemia in rats

目的探讨垂体腺苷酸环化酶激活肽(PACAP38)对大鼠水通道蛋白4(AQP4)表达的影响,以观察其减轻脑水肿的作用及其机制。方法健康雄性SD大鼠198只,随机分为假手术组(18只)、模型组(90只)和PACAP38组(90只),采用koizumi法制备大鼠局灶性脑缺血再灌注模型,利用干湿重法、免疫组织化学染色、RT-PCR分别检测脑组织含水量、AQP4及AQP4 mRNA的表达。结果与假手术组比较,模型组和PACAP38组脑组织含水量、梗死灶周围AQP4、AQP4 mRNA表达明显增加;与模型组比较,PACAP38组能显著减少脑组织含水量,减轻梗死灶周围AQP4、AQP4 mRNA表达。结论PACAP38对局灶性脑缺血大鼠具有减轻脑水肿作用,其作用机制可能与其抑制AQP4的表达有关。

Objective To observe the effect of pituitary adenylate cyclase activating polypeptide （PACAP）on brain edema after transient brain focal ischemia in rats. Mothods All rats were randomly divided into sham operation group, model group and PACAP38 treatment group. PACAP38 was administered after a 2-hour transient middle cerebral artery occlusion（MCAO） u- sing a filament mode as an intravenous bolus （20 nmol/kg） followed by an intravenous infusion using a micro-osmotic pump at a rate of 160 pmol per hour. Brain water content （BWC） was measured by dry-wet weighing method. The expression of AQP4 protein and mRNA was assessed by immunocytochemistry and reverse transcriptase polymerase chain reaction technique. Results Compared with sham operation group, BWC increased obviously 6 h after MCAO in model group and PACAP38 treatment group. BWC in PACAP38 treatment group was remarkably less than that in the model group at same time point. Expression of AQP4 protein and mRNA in penumbra area was enhanced significantly 6 h after MCAO in model group and PACAP treatment group. The level of AQP4 in treatment group was lower than that in the model group at same time point. Conclusion PACAP38 can reduce brain edema through refraining the expression of AQP4 in transient brain focal ischemia in rats.