新生鼠缺氧缺血时脑TPA活性与细胞外基质的相关性

Correlation between Activity of Tissue-type Plasminogen Activator and Extracellular Matrix in Brains of Neonatal Rats during Hypoxia-ischemia

目的 研究缺氧缺血时脑内组织型纤溶酶原激活物 (TPA)与脑微血管基膜的细胞外基质降解的相关性。 方法 一日龄 SD大白鼠分为空白对照组、假手术组和 3个缺氧缺血时间不同的实验组 (n=12 )。每组取 4例脑测 TPA活性 ,取 8例脑用抗 型胶原、层粘连蛋白和纤维粘连蛋白抗体标记。 结果 在 3个实验组中以缺氧缺血组的 TPA活性最高 ,而后随着复氧时间的增加而下降 (P<0 .0 1)。实验组的 型胶原、层粘连蛋白和纤维粘连蛋白阳性染色平均单位面积比对照组 (空白组、假手术组 )小 (P<0 .0 1)。实验组阳性产物呈不连续线状的微血管数比对照组多 (P<0 .0 1)。缺氧缺血组鼠脑严重充血水肿 ,脑重比对照组显著增加。 结论 缺氧缺血可以激发新生大白鼠脑内 TPA活性增高 ,然后通过一系列酶促反应 ,使微血管基膜的细胞外基质成分— 型胶原、层粘连蛋白和纤维粘连蛋白等降解 ,血脑屏障受损 ,微血管渗透性增加 ,发生脑水肿 ,甚至脑出血。

Objective\ To study the effect of tissue\|type plasminogen activator(TPA) in hypoxic\|ischemic brain damage.\ Methods\ Neonatal SD rats were divided into:(1)control group,(2)false operation group,(3)hypoxic\|ischemic group,(4)surviving for 24 hours after hypoxic\|ischemic group,(5)surviving for 48 hours after hypoxic\|ischemic group;n=12/each group.\ Cerebral tissues of 4 rats in each group were measured for activity of TPA.\ And cerebral tissue of 8 rats in each group were labelled with antibodies against type Ⅳ collagen,laminin or fibronectin.\ Results\ The activity of TPA in two control groups was lower than that in three experimental groups(P<0 01).\ The activity of TPA in hypoxic\|\{ischemic\} group was the highest among three experimental groups,and surviving for 48 hours group was the lowest(P<0 01).\ Average areas of positive staining of three antibodies around microvessels in three experimental groups were less than those in two control groups(P<0 01).\ The microvessel counts of discontinuous positive staining in three experimental groups were higher than those in two control groups(P<0 01).\ The brain weight of hypoxic\|ischemic group was the heaviest among five groups(P<0 05),in which cerebral edema appeared.\ The brain weight of surviving for 24 hours group was lighter than that of hypoxic\|ischemic group (P<0 05).\ The brain weight of surviving for 48 hours group was similar as two control groups.\ Conclusion\ Hypoxia\|ischemia can stimulate to rise the activity of TPA in the brain of rats.\ Then extracellular matrix\|type Ⅳ collagen,laminin and fibronectin were degraded by a series of enzyme inducing reactions,and damaged the basement membrane of cerebral microvessels.\ The permeability of microvessels was increased,so that edema of brain was aroused.\;