灯盏生脉胶囊口服结合运动训练对肾性高血压大鼠脑低密度脂蛋白相关受体蛋白-1、高度聚糖化作用终产物受体和β淀粉样蛋白1-42表达的影响

Effects of combination of Dengzhan Shengmai capsule and physical exercise on expressions of brain LRP-1, RAGE and Aβ1-42 in renovascular hypertensive rats

目的:探讨灯盏生脉胶囊口服结合运动训练对肾性高血压大鼠脑低密度脂蛋白相关受体蛋白-1(LRP-1)、高度聚糖化作用终产物受体(RAGE)蛋白和β淀粉样蛋白1-42(Aβ1-42)表达的影响。方法:雄性SD大鼠分为假手术(A)组、高血压生理盐水治疗(B)组、高血压灯盏生脉胶囊治疗(C)组、高血压运动训练(D)组、高血压灯盏生脉胶囊治疗联合运动训练(E)组,每组10只。双肾双夹法制作肾性高血压大鼠模型。灯盏生脉胶囊溶解于0.9%生理盐水中。A组只进行假手术,B组按照20mg/d·kg体重每天灌胃给生理盐水,连续4周。C组给予同剂量灯盏药液灌胃,D组跑笼运动训练,E组给予药液灌注与运动训练。采用伊文思蓝(EB)示踪法监测血脑屏障损伤程度。Western blot分析LRP-1和RAGE蛋白水平变化。ELISA法检测大鼠海马区Aβ1-42的表达。结果:与假手术组比较,各高血压组大鼠脑组织EB水平、海马区RAGE蛋白表达和Aβ1-42水平升高,而海马区LRP-1蛋白表达显著减少,差异显著(P<0.001)。给予灯盏生脉胶囊或者/和运动训练可逆转这一现象,以灯盏生脉胶囊口服结合运动训练效果最为显著(P<0.001)。结论:灯盏生脉胶囊口服结合运动训练能够改善高血压大鼠血脑屏障通透性,调节脑LRP-1和RAGE蛋白的表达,减少高血压大鼠海马区Aβ1-42沉积。

Objective：To investigate the effects of combination of Dengzhan Shengmai capsule and physical exercise on ex- pressions of brain low-density lipoprotein receptor-related protein-l（LRP-l）, receptor for advanced glycation end products （RAGE）and ]3-amyloid protein 1-42（A-31-42） in renovascular hypertensive rats （RHR）. Method：Male SD rats were randomly assigned into 5 groups （10 rats per group）： sham-operated（A） group, hy- pertension with normal saline （NS） （B） group, hypertension with Dengzhan Shengmai capsule（C） group, hyper- tension with physical exercise （D） group and hypertension with combination of Dengzhan Shengmai capsule and physical exercise （E） group. With two-kidney, two clip method, renovascular hypertensive rats models were created. Dengzhan Shengmai capsules were dissolved in sterile 0.9%NS. A group and sham operation only. In B group NS were administered （20mg/kg per day） by gavage daily for 4 weeks. In C group, Dengzhan Shenmai capsules solution were given by garage with the same volume. D group executed running exercise daily for 3 days. E group was given Dengzhan Shengmai capsules by garage and physical exercise. Blood-brain barri- er permeability and the content of A131-42 in hippocampus were detected by Evans blue （EB） leakage and ELI- SA, respectively. Western blot was used to detect the expression of LRP-1 and RAGE in the brain. Result：Compared with sham-operated group, the levels of brain EB leakage, expressions of RAGE and AI31-42 protein in the hippocampus were significantly upregulated and expression of LRP-1 protein in hippocampus was significantly down regulated in each hypertension group（P〈0.001）.Treatment with Dengzhan Shengmai cap- sule or physical exercise only or combination of Dengzhan Shengrnai capsule and physical exercise could signif- icantly reversed these conditions（P〈0.001）. The combination group E had the most significant effect. Conclusion：Combination of Dengzhan Shengmai capsule and physical exercise can improve blood-brain barrier permeability, regulate expressions of LRP-1 and RAGE and reduce accumulation of Aβ1-42 in the brain of RHR.