依普利酮对自发性高血压大鼠脑组织醛固酮与脑损害的作用

Effects of eplerenone on cerebral aldosterone level and brain lesion in spontaneous hypertension rats

目的观察自发性高血压大鼠(spontaneous hypertension rats,SHR)脑醛固酮与脑损害的关系和依普利酮(Eplererone)的作用。方法选择8周龄大鼠30只,其中SHR20只,分为SHR组(n=10)和依普利酮组(n=10),Wistar大鼠为正常组(n=10)。依普利酮组大鼠每日予依普利酮50mg/kg溶于2 ml蒸馏水灌胃,正常组和SHR组予蒸馏水2 ml灌胃。10周后,对比大鼠血压、光镜下海马、齿状回(dentate gyrus,DG)区与脑皮质病理变化、脑与血浆醛固酮和血钾等指标。结果18周龄时,SHR组和依普利酮组比正常组大鼠体重减轻(P<0.01),收缩压升高(P=0.01)。SHR组去皮质脑内醛固酮(0.2±0.06 pg/ml)高于依普利酮组(0.14±0.05 pg/ml)和正常组(0.12±0.07 pg/ml;分别P=0.044和P=0.007),但后两组比较无差异(P(0.05)。三组血浆醛固酮含量,SHR组比正常组高1.7倍(P=0.006);光学显微镜下,SHR组可见典型凋亡细胞,凋亡指数(apoptosis index,AI)为5.65±2.25,大鼠脑皮质(225.18±15.43μm),这两值和依普利酮组(240.38±12.85μm;1.84±0.76)与正常组(244.72±18.92μm;1.16±0.16)相比有差异(P<0.01);依普利酮组血清钾水平比SHR组和正常组明显升高(P≤0.05)。结论在SHR脑醛固酮含量明显增高,伴有明确的脑细胞凋亡、脑皮质变薄等脑损害表现;依普利酮可降低大鼠脑醛固酮含量,减少细胞凋亡、皮质变薄,对SHR的脑损害有预防作用,但可引起血钾的升高。

Objective To observe the relationship between cerebral aldosterone （ALD ） level and brain lesion and effect of eplerenone in spontaneous hypertension rats. Methods The rats of 8 weeks old （ n = 30） , among which 20 were spontaneous hypertension rats （ SHR ） , selected and divided into the SHR group, eplerenone group and normal group （each n = 10）. The eplerenone group was given orally the water solution of eplerenone （ 50 mg/kg dissolved in 2 ml distilled water） , and the normal group and SHR group were given 2 ml distilled water orally. After 10 weeks the pathological changes of brain hippocampus,dentate gyrus （ DG） and cortex were observed by light microscope. The blood pressure, and the indexes of cerebral and plasma ALD and serum kalium were compared. Results When the rats were 18 weeks old the rat body weight was lower （P 〈 0.01） , and systolic blood pressure increased in the SHR group and eplerenone group than those in the normal group （ P = 0.01 ）. In the SHR group the level of ALD （ 0.2 ＋ 0.06 pg/ml ） was higher than that in the eplerenone group （ 0.14 ＋ 0.05 pg/ml, P = 0. 044 ） and normal group （ 0.12 ＋ 0.07 pg/ml ,P = 0. 007）. The comparison between the eplerenone group and normal group was not different （P 〉 0.05 ）. The level of plasma ALD in the SHR group was 1.7 times higher than that in the normal group （ P = 0. 006） ,but was not deferent in the comparison between the eplerenone group and SHR group or normal group respectively. The observation outcomes by light microscope showed that typical apoptotic cells were observed in the SHR group and the apoptosis index （AI） was 5.65 ＋ 2.25, and the thickness of cerebral cortex was 225.18 ＋ 15.43 μm. The thickness of cerebral cortex was 240.38 ＋ 12.85 μm, and AI was 1.84 ＋ 0.76 in the eplerenone group,and 244.72 ＋ 18.92 μm and 1.16 ＋0.16 in the normal group. The comparison in the thickness of cerebral cortex and AI respectively was different between the SHR group and eplerenone group or normal group （P 〈 0.01 ）. The level of serum kalium in the eplerenone group was higher signifieantly than that in the SHR group or normal group （ P≤0.05 ）. Conclusion The level of cerebral ALD increased significantly in SHR accompanied by some cerebral lesion including definite apoptosis and thinned cortex. Eplerenone can reduce the level of cerebral ALD and apoptosis, relieve the cortex thinning, prevent the cerebral lesion, but induce the increase of serum kalium.