缺氧缺血性脑损伤鼠半胱氨酸天冬氨酸蛋白酶-1的表达及其意义

Expression of caspase-1 after hypoxic-ischemic brain damage

目的 研究新生鼠缺氧缺血性脑损伤 (HIBD)后半胱氨酸天冬氨酸蛋白酶 1(caspase 1)m RNA的表达及其意义。方法 将 112只新生 7d Wistar大鼠随机分为假手术对照组以及 HIBD后 3、8、2 4 h以及 3、6和 14 d组 ,每组 16只。其中 8只应用逆转录聚合酶链反应 (RT- PCR)检测病变侧脑皮质caspase- 1m RNA的表达情况 ;另外 8只进行脑组织苏木素伊红 (HE)染色 ,在光镜下观察脑组织病理变化。结果 假手术对照组中有少量 caspase- 1m RNA表达 ,HIBD 2 4 h组其表达水平开始增加 (与假手术对照组比较 P <0 .0 1) ,6 d达高峰 (与其余各组比较 P均 <0 .0 1) ,14 d时其表达下降 ,但仍高于假手术对照组(P<0 .0 1)。组织病理学检查发现 ,HIBD后 2 4 h～ 6 d神经元大量变性、坏死、丢失 ,同时胶质细胞显著增生。结论 HIBD后 caspase 1m RNA的表达增加 ,其变化规律与光镜观察到的脑损伤进展时间完全吻合 ,提示caspase -1可能参与了新生鼠 HIBD的病理损伤过程。

Objective To study the expression of caspase1 mRNA in the cerebral cortex after hypoxicischemic brain damage(HIBD) in neonatal rats. Methods One hundred and twelve 7dayold Wistar rats were domly assigned to control group, HIBD 3 hours, 8 hours, 24 hours, 3 days, 6 days and 14 days groups ( n =16 in each group), and standardized HIBD was given. In each group, 8 rats were used to assess the mRNA expression of caspase1 in cerebral cortex by semiquantitative reverse transcriptionpolymerase reaction, and another 8 rats were used to study histological changes with hematoxylineosin(HE) staining. Results The expression of caspase1 mRNA was observed in the cerebral cortex in both control and HIBD groups. After HIBD, the level of caspase1 mRNA in ischemic cortex began to increase at 24 hours ( P <0 01 vs. controls), peaked at 6 days ( P <0 01 vs. other groups) and decreased at 14 days. Histological study showed that the degenerated and necrotic neurons were increased progressively from 1 day to 6 days after HIBD, together with proliferation of glial cells. Conclusion The increased expression of caspase1 mRNA after HIBD, which was consistent with the time frame of the development of brain injury , indicates that it might play an important role in pathogenesis of HIBD in neonatal rats.