血管紧张素-(1-7)对大鼠局灶性脑缺血再灌注损伤的神经保护作用

目的 探讨血管紧张素-(1-7)Ang-(1-7)]对大鼠局灶性脑缺血再灌注损伤的保护作用.方法 对Sprague-Dawley(SD)大鼠制备大脑中动脉梗死(MCAO)模型和假手术模型,并于再灌注24 h和48 h以微型渗透泵从侧脑室给予Ang-(1-7)(100 pmol,0.5 μL/h)或人工脑脊液(aCSF)(0.5 μL/h),由此分组为假手术组(假手术+aCSF)、Ang-(1-7)治疗组MCAO+Ang-(1-7)]和aCSF治疗组(MCAO+aCSF).检测实验大鼠神经功能评分、再灌注48 h后脑水肿以及再灌注24 h后脑梗死体积,并以试剂盒测定再灌注24 h和48 h后缺血脑组织中超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量,以原位末端标记法(TUNEL)检测再灌注48 h后脑梗死灶周围组织神经细胞凋亡数.结果 Ang-(1-7)治疗MCAO模型大鼠,能显著改善神经功能评分(P<0.05)、缩小脑梗死体积(P<0.05)、降低组织MDA含量(P<0.05)、提高组织SOD活性(P<0.01),并明显减少脑梗死灶周围组织神经细胞凋亡数(P<0.01),但对脑组织含水量无明显影响作用.结论 Ang-(1-7)可能通过抗氧化应急反应、减轻神经细胞凋亡程度等实现治疗缺血再灌注损伤、神经保护作用.

Neuroprotective effect of angiotensin-(1-7) against focal cerebral ischemic-reperfusion injury in rats

Objective To investigate the protective effects ofAngiotensin-(1-7) Ang-(1-7)] against the focal cerebral ischemic-reperfusion injury in rats. Methods Spragne-Dawley rats were randomly divided into sham operated group, Ang-(1-7) treated group and aCSF treated group. The latter 2 groups were subjected to middle cerebral artery occlusion (MCAO). The 3 groups were administrated artificial cerebrospinal fluid (aCSF, 0.5 μL/h), Ang-(1-7) (100 pmol, 0.5 μL/h) and aCSF 0.5 μL/h,respectively, by implanted Alzet osmotic minipumps into lateral cerebral ventricle at reperfusion 24 h and 48 h. In all experimental rats, their neurological function scores, the brain edema at reperfusion 48 h and the cerebral infarct size at reperfusion 24 h were evaluated. And the malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in the ischemic cerebral tissue at reperfusion 24 h and 48 h were also determined. The number of apoptotic neurons within the tissue around the infarct at reperfusion 48 h was detected by the way of staining with terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick-end labeling (TUNEL). Results In the treatment of MCAO rats, Ang-(1-7) significantly ameliorated their neurological function score (P＜0.05), reduced the infarct size (P＜0.05), decreased the tissue MDA content (P＜0.05), increased the tissue SOD activity (P＜0.05). It also reduced markedly the number of apoptotic neurons around the infarct (P＜0.01), but had no effect on the water content in the brain. Conclusions Ang- (1-7) has a neuroprotective effect against cerebral ischemic-reperfusion injury, perhaps by its anti-oxidation stress and inhibition of neuronal apoptosis.