阿托伐他汀对高胆固醇血症患者血小板血管紧张素Ⅱ受体表达的影响

The Effects of Atorvastatin on the Expression of Angiotensin Ⅱ Receptors in Platelets in Patients with Hypercholesterolemia

目的通过观察高胆固醇血症患者血小板血管紧张素Ⅱ1型受体(A T_1 R)、血管紧张素Ⅱ2型受体(AT_2R)表达的变化及阿托伐他汀对其表达变化的影响,探讨肾素血管紧张素系统(RAS)在高血压及动脉粥样硬化(AS)发生中的作用及他汀多效性作用的机制。方法在我院健康查体中心随机选取健康对照60例和高胆固醇血症患者80例,分别为对照组和高脂组;高脂组予以阿托伐他汀20 mg/d,睡前口服,共12周。于试验开始前及高脂组服药12周时,肘静脉取血,分离血清、血浆并提取血小板。放射免疫法检测血浆的血管紧张素Ⅱ(AngⅡ)水平,RT-PCR 和 Western blot 方法分别检测血小板 A T_1R、AT_2R 的 mRNA 和蛋白质表达水平。结果阿托伐他汀组的胆固醇相较高脂组明显降低(他汀组:5.57±1.27比高脂组:7.08±1.23 mmol/L,P<0.05):①高脂组的血浆AngⅡ水平较对照组显著升高(P<0.01),他汀治疗后较治疗前明显降低(P<0.05)。②阿托伐他汀治疗明显下降高脂组血小板的 AT_1R mRNA(治疗前:0.93±0.22比治疗后:0.52±0.13,P<0.01)和蛋白质表达(治疗前:1.35±0.32比治疗后:0.72±0.16,P<0.01)。③阿托伐他汀治疗明显升高高脂组血小板的 AT_2R mRNA(治疗前:0.85±0.16比治疗后:1.24±0.28,P<0.01)和蛋白质表达(治疗前:0.81±0.1 7比治疗后:1.23±0.25,P<0.01)。④高脂组血小板 AT_1R、AT_2R 的表达均与血浆的 AngⅡ水平呈显著正相关(r=0.389,P<0.01;r=0.356,P<0.01)。结论阿托伐他汀下调高胆固醇血症患者血小板 AT_1R 表达的增高,但进一步上调 AT_2R 表达的增高。

Objective To investigate the changes in angiotensin Ⅱ type 1 receptor（AT1R） and type 2 receptor （ AT2R） expression in platelets in patients of hypercholesterolcmia and the effects of atorvastatin. Methods Eighty patients with hypercholesterolemia and sixty healthy persons were recruited. Atorvastatin （20 mg/d} were administed in hyperlipidemia patients for twelve weeks. The level of plasma angiotensin Ⅱ （ Ang Ⅱ ） was detected by the method of radioimmunoassay. The platelet expression of AT1R mRNA and protein were assessed by reverse transcription polymerse chain reaction （RT-PCR） and Western blot. Results Atorvastatin lowered cholesterol in hyperlipidemia patients（cholesterol, 5.57±1. 27 vs 7.08±1.23 mmol/L, P〈0.05）. （1）The plasma Ang Ⅱ of hyperlipidemia patients was higher than that of controls （P〈0.01）hut atorvastatin lowered plasma Ang Ⅱ （P〈0.05）. （2）The platelet AT1R mRNA and protein expression were also higher in hyperlipidemia patients than those of controis（ All P〈0.01）, atorvastatin decreased the AT1R mRNA and protein expression in platelets（ AT1R mRNA,0.93±0.22 vs 0.52±0.13;AT1R protein expression, 1.35±0.32 vs 0.72±0.16, P〈0.01）. （3）The expression of AT2 R mRNA and protein on platelets were also higher in hyperlipidemia patients than those of controls（P〈0.01）,atorvastatin increased both of them in platelet （ AT2R mRNA, 0.85 ± 0.16 vs after treatment ： 1.24 ± 0.28 ; AT2R protein expression, 0. 81±0. 17 vs after treatment： 1.23±0.25, P〈0. 01）. （4）The expression of platelet AT1R and AT2R protein were directly correlated with the level of plasma Ang Ⅱ （All, P〈0. 01 ） in patients with hypercholesterolemia. Conclusion Atorvastatin downregulate the increased AT1R mRNA and protein expression, hut upregulate the increased AT2 R mRNA and protein expression in platelets in patients with hypercholesterolemia.