局部应用重组水蛭素对大鼠脑出血神经细胞凋亡的干预作用

Intervention effect of local application of recombinant hirudin on neuronal apoptosis in intracerebral hemorrhage of rats

目的研究局部应用重组水蛭素对大鼠脑出血神经细胞凋亡的干预作用。方法采用自体血二次注入法建立大鼠脑出血模型,应用凝血酶的特异抑制剂重组水蛭素进行干预,并对大鼠神经功能缺损程度进行评分;分别测定同侧皮质和基底节区TdT介导的dUTP缺口末端标记(TUNEL)阳性细胞以及caspase3免疫反应性(IR)细胞的表达。结果水蛭素干预后,大鼠神经功能缺损程度减轻(P<0.01),同侧基底节区和皮质TUNEL阳性细胞、caspase3免疫反应性IR细胞减少(均P<0.01),尤以同侧皮质减少明显(均P<0.001)。结论水蛭素可明显减少大鼠脑出血后的细胞凋亡数量,减轻大鼠神经功能缺损程度;凝血酶释放很可能是脑出血神经细胞凋亡的机制之一。

Objective To investigate the intervention effect of recombinant hirudin on apoptosis of neurons in intracerebral hemorrhage （ICH） of rats. Methods ICH animal models were established by autologous blood injection, and hirudin, a special inhibitor of thrombin, was used for intervention treatment. The neurologic impairment scores （NIS） of rats were measured, and TUNEL-positive cells and caspase-3 IR cells were also detected in cortex and basal ganglia 24 h after operation. Results After intervention treatment of recombined hirudin, the NIS of rats decreased obviously （P 〈0. 01 ）, and the numbers of TUNEL-positive cells and caspase-3 IR cells were also significantly decreased both in ipsilateral cortex and basal ganglia （P 〈0. 01 ） , especially in the area of cortex （P 〈 0. 001 ）. Conclusions Hirudin may decrease the number of neuronal apoptosis and relieve neurologic impairment in ICH of rats. Which indicates that release of thrombin may be one of the mechanisms underlying neuronal apoptosis after ICH.