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目的观察降血脂药普伐他汀对慢性脑缺血(CVI)大鼠脑海马区早老素-1(PS-1)蛋白水平的影响。方法36只雄性Wistar大鼠随机分为正常对照组(7只),高脂饮食组随机分为空白对照组(6只)、普伐他汀组(7只)、单纯脑缺血组(7只)及脑缺血+普伐他汀组(9只)。采用永久性结扎双侧颈总动脉建立CVI模型。于术后2个月测血脂,行酶联免疫吸附试验(ELISA)检测血浆及脑左侧海马区匀浆中β淀粉样蛋白(Aβ)水平,蛋白免疫印迹检测海马区PS-1改变。结果⑴高脂饮食导致大鼠血浆胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白(LDL-C)显著升高。普伐他汀可使TC降至接近正常水平,LDL-C有不同程度下降,TG无明显改善。⑵各实验组血浆Aβ水平无统计学差异。脑海马区匀浆中,空白对照组、普伐他汀组Aβ轻度升高,而脑缺血组显著升高(P<0.01),普伐他汀可以有效降低脑缺血组Aβ水平(P<0.01)。蛋白免疫印迹结果显示高脂饮食组、空白对照组及脑缺血组PS-1全长蛋白明显上调(P<0.05),而普伐他汀组、脑缺血+普伐他汀组PS-1蛋白可降至接近正常水平。结论降血脂药物普伐他汀在降低脑缺血后Aβ产生的同时抑制了PS-1的表达上调,可能对阿尔茨海默病有一定的防治作用。
Objective To observe the effects of hypolipidemic pravastatin on the protein expression of pre-sen-1 (PS-1) in the hippocampus of rats with chronic cerebral ischemia (CVI). Methods Thirty - six male Wistar rats were randomly divided into normal control group (n = 7), high fat diet group (n = 6), pravastatin group (n = 7), cerebral ischemia group ) And cerebral ischemia + pravastatin group (n = 9). CVI model was established by permanent ligation of bilateral common carotid arteries. Serum lipids were measured at 2 months after operation. The levels of amyloid beta protein (Aβ) in plasma and left hippocampal homogenate were detected by enzyme-linked immunosorbent assay (ELISA). The level of PS-1 in hippocampus was detected by Western blotting. Results (1) High fat diet resulted in significant increase of plasma cholesterol (TC), triglyceride (TG) and low density lipoprotein (LDL-C) in rats. Pravastatin can make TC down to near normal levels, LDL-C decreased to varying degrees, TG no significant improvement. ⑵ There was no significant difference in plasma Aβ levels among experimental groups. In hippocampus homogenate, Aβ in blank control group and pravastatin group increased slightly, but was significantly increased in cerebral ischemia group (P <0.01). Pravastatin could effectively reduce the level of Aβ in cerebral ischemia group (P < 0.01). Results of western blotting showed that PS-1protein in high-fat diet group, blank control group and cerebral ischemia group were significantly increased (P <0.05), while PS-1protein in pravastatin group, cerebral ischemia + pravastatin group Can be reduced to near normal levels. Conclusions Pravastatin, a lipid-lowering drug, can inhibit the up-regulation of Aβ production and reduce the expression of PS-1 after cerebral ischemia, which may have some preventive and therapeutic effects on Alzheimer’s disease.