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目的探讨瑞舒伐他汀钙对慢性高血压大鼠的脑白质病变及其空间认知功能障碍的影响。方法雄性Sprague-Daw Iey大鼠49只,随机分为假手术组、高血压组和瑞舒伐他汀钙治疗组(10 mg/kg)。高血压组和瑞舒伐他汀钙治疗组采用双肾双夹法制作易卒中型肾血管性高血压大鼠(stroke-prone renovascular hypertensive rat,RHRSP)模型,定期监测血压。水迷宫实验检测空间记忆功能;Luxol fast blue染色观察脑白质疏松程度;免疫荧光法观察额叶皮层β-淀粉样蛋白(β-amyloid,Aβ)在大脑皮层的沉积分布;原位末端转移酶标记染色法(Td T-mediated d UTP-biotin nick end labeling,TUNEL)观察额叶皮层细胞凋亡水平。结果 RHRSP大鼠造模后血压逐渐升高,明显高于假手术组(P<0.01);瑞舒伐他汀钙较高血压组逃避潜伏期时间明显缩短(P<0.01),3组大鼠跨越平台次数分别为(4.55±1.23)、(1.00±0.80)、(3.79±0.95),差异有统计学意义(P<0.01)。与高血压组相比,瑞舒伐他汀钙可改善脑白质疏松程度(P<0.01),减少额叶皮层区Aβ沉积(17.47±3.59 vs.4.42±1.57,P<0.01)及细胞凋亡(37.84±4.73 vs.14.42±2.43,P<0.01)。结论瑞舒伐他汀钙可改善慢性高血压大鼠的脑白质病变,减少额叶皮层区Aβ沉积以及细胞凋亡从而保护大鼠的空间记忆功能。
Objective To investigate the effect of rosuvastatin calcium on white matter lesions and spatial cognitive dysfunction in chronic hypertensive rats. Methods 49 male Sprague-Daw Iey rats were randomly divided into sham operation group, hypertension group and rosuvastatin calcium treatment group (10 mg / kg). Hypertension group and rosuvastatin calcium treatment group were treated with double-kidney double-clip method to make stroke-prone renovascular hypertensive rat (RHRSP) model, and blood pressure was monitored regularly. The water maze test was used to detect spatial memory function; Luxol fast blue staining was used to observe the degree of leukoaraiosis; the deposition distribution of β-amyloid (Aβ) in the cerebral cortex was observed by immunofluorescence; the in situ terminal transferase (TdT-mediated dUTP-biotin nick end labeling, TUNEL) to observe the level of apoptosis in frontal cortex. Results The blood pressure of RHRSP rats increased gradually after modeling, which was significantly higher than that of sham operation group (P <0.01). The escape latency time of rosuvastatin calcium-induced hypertension group was significantly shortened (P <0.01) (4.55 ± 1.23), (1.00 ± 0.80) and (3.79 ± 0.95) respectively, the difference was statistically significant (P <0.01). Compared with hypertension group, rosuvastatin calcium can improve the degree of white matter (P <0.01), reduce the deposition of Aβ in frontal cortex (17.47 ± 3.59 vs.4.42 ± 1.57, P <0.01) and apoptosis 37.84 ± 4.73 vs.14.42 ± 2.43, P <0.01). Conclusion Rosuvastatin calcium can improve the white matter of chronic hypertensive rats, reduce Aβ deposition in frontal cortex and apoptosis so as to protect the spatial memory of rats.