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目的 研究长期口服血管紧张素 1受体拮抗剂氯沙坦对卒中易感型自发性高血压大鼠(SHRsp)的脑保护机制。 方法 6周龄雄性SHRsp 2 6只 ,随机分为生理盐水、小剂量氯沙坦 (10mg·kg 1·d 1)和大剂量氯沙坦 (30mg·kg 1·d 1) 3组 ,以 8只 6周龄雄性京都Wistar大鼠 (WKY)作为正常对照 ,记录体重、血压和脑卒中临床表现评分 ,18周后断头处死 ,光镜和电镜观察脑组织结构 ;TUNEL法检测神经细胞凋亡。 结果 18周后SHRsp大剂量用药组血压 (16 9 4± 10 1)mmHg明显低于未用药组 (2 2 5 5± 6 8)mmHg ,(P <0 0 5 ) ,小剂量用药组血压 (2 16 7± 8 3)mmHg ,与对照组比较改变不明显 (P >0 0 5 ) ;SHRsp未用药组脑卒中评分 (3 5± 0 6 )显著高于小剂量用药组 (0 7± 1 1)和大剂量用药组 (0 4± 0 7) ,(P <0 0 5 ) ;上述 3组神经元凋亡率分别为 :5 2 0± 16 7、14 0±4 4、13 9± 4 3,SHRsp未用药组神经元凋亡率高于小剂量和大剂量用药组 ,差异有显著性(P <0 0 5 )。 结论 氯沙坦能降低SHRsp脑卒中发生率、减少SHRsp神经细胞凋亡 ,此作用与血压无关。
Objective To study the long-term oral administration of losartan, an angiotensin 1 receptor antagonist, on the neuroprotective mechanism of stroke-prone spontaneously hypertensive rats (SHRsp). Methods Six 6-week-old male SHRsp 2 were randomly divided into three groups: normal saline, losartan 10 mg · kg -1 · d -1 and losartan 30 mg · kg -1 · d -1 Six-week-old male Wistar rats (WKY) were used as normal control to record body weight, blood pressure and stroke clinical scores. After 18 weeks, the rats were sacrificed and the brain tissues were observed under light microscope and electron microscope. TUNEL method was used to detect neuronal apoptosis . Results After 18 weeks of treatment, the blood pressure (16 9 4 ± 10 1) mmHg in the SHRsp high dose group was significantly lower than that of the untreated group (2255 ± 68) mmHg (P 0 05) 2 16 7 ± 8 3 mmHg, which was not significantly different from the control group (P> 0.05). The stroke score of SHRsp non-medication group (35 ± 0 6) was significantly higher than that of the low-dose medication group (0 7 ± 1 1) and high-dose group (0 4 ± 0 7), (P <0 05). The apoptosis rates of the above three groups were respectively 52 0 ± 16 7, 14 0 ± 4 4, 13 9 ± 4. The apoptotic rate of neurons in SHRsp untreated group was higher than that in low dose and high dose groups (P <0.05). Conclusion Losartan can reduce the incidence of stroke in SHRsp and decrease the apoptosis of SHRsp nerve cells. This effect has nothing to do with blood pressure.