氯沙坦对卒中易感型自发性高血压大鼠的脑保护作用

Effect of Lorsartan on stroke in strokeprone spontaneously hypertensive rat

目的 研究氯沙坦对卒中易感型自发性高血压大鼠(SHRsp)脑保护作用的机制。方法 6周龄雄性SHRsp随机分为生理盐水组、小剂量氯沙坦组(10mg·kg-1·d-1)和大剂量氯沙坦组(30mg·kg-1·d-1),记录血压和脑卒中临床表现评分,18周后处死,光镜观察脑卒中的发生率和脑血管结构;电镜观察脑组织的超微结构;TUNEL法检测神经细胞凋亡。结果 大剂量氯沙坦组血压明显低于未用药组(P<O.05),小剂量氯沙坦组血压改变不明显(P>O.05)。对照组SHRsp死亡率、脑动脉中膜厚度/管腔半径的比值和神经细胞凋亡率均高于小剂量和大剂量氯沙坦组,差异均有显著性意义(P<O.O5)。结论 氯沙坦可通过于预SHRsp血管重构和减少神经细胞凋亡发挥脑血管保护作用,此作用与血压无关。

Objective To investigate the preventive effects of Lorsartan on stroke in strokeprone spontaneously hypertensive rat (SHRsp). Methods SHRsp were divided into Lorsartan 30mg. kg-1. d-1 group,10mg. kg-1. d-1 group and vehicle group. The systolic blood pressure was measured by tail-cuff sphygmomanometry and clinical score of stroke was recorded. The coronal brain sections and cerebro-arteria histopathologic examination was made by microscope and electron microscope. Apoptosis was analyzed by TdT-mediated dUTP-biotin nick end labeling. Results Lorsartan 30mg/kg-1. d-1 delayed the development of severe hypertension and prevented stroke in SHRsp. Lorsartan 10mg/kg-1. d-1 did not affect systolic blood pressure but prevented stroke. Lorsartan treatment groups showed smaller lumen and cross-sectional area of the cerebro-arteria in comparison to vehicle group (P<0. 05, respectively). The number of cells exhibiting apoptosis was lower in Lorsartan treatment groups than in vehicle group (P<0. 05). Conclusion Chronic AT1 receptor antogonist therapy with Lorsartan markedly reduces both hypertension and brain damage by preventing the development of cerebrovascular lesion and apoptosis in SHRsp in the absence of a blood pressure fall.