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凝血酶对大鼠脑出血后血肿周围组织继发性脑损伤的影响。

Effects of thrombin on the secondary cerebral injury of perihematomal tissues of rats after intracerebral hemorrhage.

作者信息

Liu C M, Shi B Z, Zhou J S

机构信息

Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.

Yuhua Hospital of Yuhuatai District, Nanjing City, China.

出版信息

Genet Mol Res. 2014 Jun 18;13(2):4617-26. doi: 10.4238/2014.June.18.4.

Abstract

This study aimed to investigate the effects of thrombin released in hematoma after intracerebral hemorrhage (ICH) on the cerebral injury of perihematomal tissues and to evaluate the protection effect of hirudin on the cerebral injury after ICH. We used the autologous uncoagulated blood injection method to prepare the ICH rat model, and all rats were randomly divided into a normal group, an ICH group, or a hirudin group. At different time points, rat heads were cut to harvest brain sections. Immunohistochemical staining, histochemical staining, and hematoxylin and eosin staining were conducted for CD34, microglia, and neutrocytes. CD34-positive microvessels were most abundant in brain tissues of the sham-operation group. At 12 h after ICH, CD34 expression reduced and reached the minimum level at 72 h (P<0.01). At 6 h after ICH, microglia expression was visible and reached a peak at 48 h (P<0.01). At 12 h after ICH, neutrocyte infiltration was visible and the number was greatest at 48 h (P<0.01). The early application of hirudin after ICH could significantly reduce microglia and neutrocyte expression and could significantly slow down the CD34 decrease trend (P<0.01). However, hirudin application in the edematization stage after ICH did not significantly increase CD34- positive microvessel abundance (P>0.05). A thrombin-mediated inflammatory reaction is involved in the cerebral injury after ICH, and the early application of hirudin has a protective effect.

摘要

本研究旨在探讨脑出血(ICH)后血肿中释放的凝血酶对血肿周围组织脑损伤的影响,并评估水蛭素对ICH后脑损伤的保护作用。我们采用自体未凝血血液注射法制备ICH大鼠模型,将所有大鼠随机分为正常组、ICH组或水蛭素组。在不同时间点,断头取大鼠脑切片。对CD34、小胶质细胞和中性粒细胞进行免疫组织化学染色、组织化学染色及苏木精-伊红染色。假手术组脑组织中CD34阳性微血管最为丰富。ICH后12 h,CD34表达降低,72 h时降至最低水平(P<0.01)。ICH后6 h可见小胶质细胞表达,48 h时达到峰值(P<0.01)。ICH后12 h可见中性粒细胞浸润,48 h时数量最多(P<0.01)。ICH后早期应用水蛭素可显著降低小胶质细胞和中性粒细胞表达,并可显著减缓CD34下降趋势(P<0.01)。然而,ICH后水肿期应用水蛭素并未显著增加CD34阳性微血管丰度(P>0.05)。凝血酶介导的炎症反应参与了ICH后脑损伤,早期应用水蛭素有保护作用。

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