摘要目的 观察垂体腺苷酸环化酶激活肽(pituitary adenylate cyclase activating peptide,PACAP)对脑缺氧缺血(hypoxic-ischemic brain damage,HIBD)新生大鼠胱冬酶-3和x-连锁凋亡抑制蛋白(x-linked inhibitor of apoptosis protein,XIAP)的影响,探讨其脑保护作用和有效剂量.方法 60只新生大鼠随机分为假手术组、生理盐水对照组以及PACAP大剂量组(10-8 mol)、中等剂量组(10-9 mol)和小剂量组(10-8 mol),建立HIBD动物模型.应用实时荧光定量聚合酶链反应法榆测新生大鼠HIBD后24 h损伤侧脑组织的胱冬酶-3 mRNA和XIAP mRNA表达情况,应用分光光度法检测胱冬酶-3活性.结果 在HIBD后24 h,生理盐水对照组胱冬酶-3 mRNA表达和酶活性以及XIAP mRNA表达均显著高于假手术组(P均<0.01);PACAP各剂量组胱冬酶-3 mRNA表达和酶活性均显著低于生理盐水对照组(P均<0.01),而XIAP mRNA表达均显著高于牛理盐水对照组(P均<0.01).结论 PACAP能上调XIAP mRNA表达,抑制胱冬酶-3 mRNA表达和酶活性,对新生大鼠HIBD具有保护作用,而且在大剂量、中等剂量和小剂量时均有效.

abstractsObjective To observe the effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on the expressions of caspase-3 and X-linked inhibitor of apoptosis protein (XIAP) after hypoxic-ischemic brain damage (HIBD) in neonatal rats and to investigate its neuroprotection and effective dose. Methods Sixty neonatal rats were randomly allocated to one of three groups: sham operation, saline control and PACAP groups. The PACAP group was redivided into high (10-8 mol), medium (10-9 mol) and low (10-12 mol) dose groups. An animal model of HIBD was established. Real-time fluorescent quantitative polymerase chain re-action method was used to detect the expressions of caspase-3 mRNA and XIAP mRNA on af-fected side of brain 24 hours after HIBD in neonatal rats, and spectrophotometry was used to detect the activities of caspase-3. Results Twenty-four hours after HIBD, caspase-3 mRNA expression and enzyme activity, as well as XIAP mRNA expression in the saline control group were increased significantly compared to the sham operation group (all P <0.01). Caspase-3 mRNA expression and enzyme activity in all the PACAP groups were significantly lower than those in the saline control group (all P <0.01), while XIAP mRNA expression was significantly higher than that in the saline control group (all P < 0.01 ). Conclusions PACAP may upregu-late XIAP mRNA expression, inhibit caspase-3 mRNA expression and enzyme activity. It has neuroprotective effect on HIBD in neonatal rats, and it is effective with high, medium and low doses.