丁咯地尔对局灶性脑缺血大鼠内皮素及降钙素基因相关肽含量的影响

Effect of buflomedil hydrochloride on endothelin and calcitonin gene-related peptide levels in focal cerebral ischemia in rats

目的探讨丁咯地尔对局灶性脑缺血大鼠的保护作用及其机制。方法选用健康雄性SD大鼠30只,将其随机分为假手术组,单纯缺血组,丁咯地尔5、10、20mg/kg组,每组6只大鼠。用线栓法制作大鼠大脑中动脉阻塞模型,于24h后进行神经功能评分,并检测脑组织内皮素、降钙素基因相关肽(CGRP)含量。结果丁咯地尔5、10及20mg/kg组神经功能缺损评分分别为1·83±0·41、1·67±0·82、1·50±0·55,与单纯缺血组的3·00±0·63比较,差异有显著性(P<0·05,P<0·01,P<0·01);内皮素含量分别为(169±39)、(155±42)、(144±27)pg/ml,与单纯缺血组的(217±51)pg/ml比较,差异有显著性(P<0·05,P<0·01,P<0·01);CGRP含量分别为(150±44)、(170±44)、(173±54)pg/ml,与单纯缺血组的(96±40)pg/ml比较,差异有显著性(P<0·05,P<0·01,P<0·01),且呈量效关系。结论丁咯地尔对局灶性脑缺血所造成的大鼠神经功能损伤具有保护作用,其机制可能与降低脑缺血后脑组织中异常升高的内皮素、增加脑组织中CGRP的含量有关。

Objective To discuss the neuroprotective effect of buflomedil hydrochloride after focal cerebral ischemia in rats and its mechanism. Methods Thirty healthy male SD rats were randomly divided into sham-operation, pure ischemia, buflomedil hydrochloride 5 mg/kg, 10 mg/kg and 20 mg/kg treated groups （ n = 6 in each group）. The model of middle cerebral artery （MCA） occlusion was prepared using the intraluminal thread method. The neurological deficit score was evaluated ; the levels of endothelin and calcitonin gene-related peptide （CGRP） in brain tissues were measured after 24 hours. Results Neurological deficit scores in the buflomedil hydrochloride 5, 10 and 20 mg/kg groups were 1.83 ± 0. 41, 1.67 ±0. 82 and 1.50 ±0. 55, respectively. As compared with 3.0 ± 0. 63 in the pure ischemia group, there were significant differences （P 〈0. 05, P 〈0. 01 and P 〈0. 01 ） ; the levels of their endothelin were 169 ±39, 155 ±42 and 144 ±27 pg/ml, respectively. As compared with 217 ±51 pg/ml in the pure ischemia group, there were significant differences （ P 〈 0. 05, P 〈 0. 01 and P 〈 0. 01 ） ; and the levels of their CGRP were 150 ±44, 170 ±44 and 173 ±54 pg/ml, respectively. As compared with 96 ±40 pg/ml in the pure ischemia group, there were significant differences （ P 〈 0. 05, P 〈 0. 01 and P 〈 0. 01 ）. It showed that there was a dose-effect relationship between them. Conclusion Buflomedil hydrochloride may have neuroprotective effect on neurological injury caused by focal cerebral ischemia, and its mechanism may be associated with the reducing of abnormally increased endothelin and the increased levels of CGRP in brain tissues after cerebral ischemia.