辛伐他汀逆转左室肥厚的作用与抑癌基因PTEN表达的关系  

The Effect of Simvastatin on the Regression of Left Ventricular Hypertrophy and Its Relationship with PTEN Expression

作　　者：陈永清[1] 赵连友[1] 郑强荪[1] 李言川[1] 尚福军[1] 李爱国[1] 王斌[1] 

机构地区：[1]第四军医大学唐都医院心内科,陕西西安710038

出　　处：《高血压杂志》2005年第6期353-357,共5页Chinese Journal of Hypertension

基　　金：陕西省科学技术研究发展计划项目资助课题[2002K10-G1(23)]。

摘　　要：目的观察辛伐他汀逆转自发性高血压大鼠(SHR)左心室肥厚(LVH)的作用及其与抑癌基因第10号染色体缺失的张力蛋白同源区(PTEN)表达的关系。方法16只雄性8周龄SHR测量体重和收缩压后,随机分为SHR治疗组和SHR对照组,分别给予辛伐他汀和安慰剂灌胃治疗,性别、年龄、数量匹配的Wistar大鼠给予安慰剂治疗作为正常对照组,疗程10周,观察辛伐他汀对大鼠收缩压和左心室重量/体重比值(LVW/BW)的影响,采用逆转录聚合酶链式反应(RTPCR)和蛋白免疫印迹法(Westernblot)检测辛伐他汀对心肌组织PTEN表达的影响。结果(1)治疗前两组SHR收缩压无显著差异(P>0.05),均高于Wistar正常对照组大鼠(P<0.01);给予辛伐他汀后,SHR治疗组收缩压(217.3±8.5)mmHg较SHR对照组(220.8±9.9)mmHg略有降低,但无统计学意义(P>0.05),且两组SHR收缩压仍高于Wistar正常对照组大鼠(126.0±5.8)mmHg,差异非常显著(P<0.01)。(2)SHR对照组大鼠的LVM/BW(4.10±0.13)mg/g明显高于Wistar正常对照组(3.04±0.12)mg/g,并有统计学意义(P<0.01),而SHR辛伐他汀治疗组的LVM/BW(3.73±0.08)mg/g较SHR对照组明显下降(P<0.01)。(3)SHR对照组大鼠心肌组织PTEN的mRNA表达水平(0.36±0.04)低于Wistar正常对照组(0.87±0.05),差异非常显著(P<0.01),SHR治疗组大鼠的PTENmRNA表达水平(0.60±0.05)较SHR对照组显著升高,并有统计学意义(P<0.01)。(4)Wistar正常对照组、SHR对照组和SHR治疗组大鼠心肌组织PTEN蛋白表达水平分别为50.53±2.92、24.65±3.89和40.32±4.04,其中SHR对照组明显低于Wistar正常对照组(P<0.01),SHR治疗组则较SHR对照组显著升高(P<0.01)。结论辛伐他汀能够逆转SHR的LVH,其机制可能与PTEN表达水平增加有关。ObjectiveTo study the effect of simvastatin on the regression of left ventricular hypertrophy(LVH)and its relationship with the expression of phosphatase and tensin homolog deleted on chromosome ten(PTEN) in spontaneously hypertensive rats(SHR).MethodsSixteen male SHR of 8 weeks old were randomized to SHR treatment group (n=8, simvastatin 10 mg/d by gavage) or SHR control group (n=8) for 10 weeks.Age matched male Wistar rats were served as controls.After treatments, SBP and ratio of left ventricle mass to body weigh(LVM/BW)were measured.The PTEN mRNA expression level and protein in myocardium were determined with reverse transcription polymerase chain reaction(RT-PCR)and Western blot.ResultsAfter treatments, SBP in both SHR groups [control : (220.8±9.9)mm Hg, treatment: (217.3±8.5)mm Hg] were higher than that of Wistar rats group(126.0±5.8)mm Hg.2. LVM/BW was lowered in treated SHR (3.73±0.08)mg/g, compared with SHR control group (4.10±0.13)mg/g (P<0.01).3. The expression of PTEN mRNA was significantly increased in SHR treatment group(0.60±0.05)ID than that in SHR control group (0.36±0.04)ID, but was significantly lower than that of Wistar rats (0.87±0.05)ID, (P<0.01).4. The protein level of PTEN was greatest in Wistar rats (50.5±2.92)ID and lowest in control SHR (24.6±3.9)ID, while treatment increased the PTEN protein significantly (40.3±4)ID, (P<0.01).ConclusionSimvastatin reverse LVH in SHR, which was associated with the increase of expression level of PTEN in myocardium.

关 键 词：PTEN表达 辛伐他汀 抑癌基因 逆转左室肥厚 自发性高血压大鼠(SHR) 逆转录聚合酶链式反应 正常对照组 Wistar大鼠 mRNA表达 蛋白免疫印迹法 心肌组织 蛋白表达水平 治疗组 染色体缺失 左心室肥厚 收缩压 安慰剂治疗 左心室重量 

分 类 号：R541.3[医药卫生—心血管疾病]