苯那普利对5/6肾切除大鼠肾脏血管紧张素Ⅱ及时钟基因表达节律的影响  

Effect of Benazepril on Kidney AngiotensinⅡand Clock Genes in 5/6 Nephretomy Rats

作　　者：黄小妹[1] 陈文莉[1] 袁静萍[2] 杨月红[2] 王银[1] 胡晓松[1] 曾星若[1] 方询[1] 

机构地区：[1]武汉市中心医院肾病科,武汉430014 [2]武汉市中心医院病理科,武汉430014

出　　处：《华中科技大学学报（医学版）》2013年第5期535-540,共6页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：湖北省卫生厅科研立项(No.2012Z-B08);武汉市卫生局科研资助项目(No.WX12C10)

摘　　要：目的 观察苯那普利对5/6肾切除大鼠肾组织血管紧张素Ⅱ（AngⅡ）、时钟基因及其蛋白产物表达节律的影响.方法 SPF级雄性Wistar大鼠,随机分为3组：假手术组,5/6肾大部切除组（模型组）,苯那普利组（BM组）.大鼠在恒温（22±2）℃,12 h-12 h明暗交替的环境中饲养12周.早7AM开灯,记为ZT0时,依次类推,晚7PM时关灯,记为ZT12时.12周时分别自ZT0时起每4小时各组分别处死5只大鼠并留取血及肾组织用放免法检测血浆及肾组织AngⅡ节律,用real-time PCR及Western blot方法检测肾组织时钟基因（per2、bmal1及dbp）及其蛋白（PER2、BMAL1及DBP）的表达水平及节律.结果 ①肾及血浆AngⅡ节律不同;BM组血浆及肾AngⅡ水平下降,肾AngⅡ峰值时间延后6～8 h,振幅减弱.②假手术组和模型组bmal1 mRNA谷峰值点相同,模型组per2 mRNA峰值时间提前4 h;BM组bmal1 mRNA峰值时间后移4 h,dbp及per2 mRNA 近日节律消失.③肾时钟蛋白模型组BMAL1及DBP振幅增强,PER2及BMAL1峰值均提前4 h;BM组BMAL1及DBP的节律及振幅与假手术组相似.④假手术组和模型组肾AngⅡ与肾时钟基因bmal1 mRNA表达呈正相关.结论 苯那普利改变5/6肾切除鼠肾AngⅡ水平及节律,也改变其肾时钟基因及其蛋白的表达节律.肾素-血管紧张素系统（RAS）与肾近日节律系统的相互作用可能是苯那普利延缓慢性肾病（CKD）进展的机制之一.Objective To investigate the rhythmic expression of clock genes and proteins in the kidney of 5/6 nephrectomy （STNx） rats and the impact of benazepril on them. Methods Male Wistar rats were randomly divided into sham STNx group （sham group） ,STNx group （model group） and benazepril group （BM group）. They were housed in a temperature-controlled room （22±2）℃ and synchronized to the light-dark cycle of 12 ： 12 for 12 weeks with light on from 7：00 a. m. [zeitgeber time （ZT） 0]. On week 12 ,the plasma and kidney tissues were collected every 4 h throughout the day to detect the expression of angiotensin Ⅱ （Ang Ⅱ ） by radioimmunoassay （RIA） ,and rhythmic expression of clock genes （per2 ,bmall and dbp） and proteins （BMAL1,PER2 and DBP） by real-time PCR and Western blot. Results ①The rhythmic expression of Ang Ⅱ in the plasma was different from that in the kidney tissues. In BM group compared with sham group and model group and model group, the level of Ang Ⅱ was decreased in both the plasma and the remnant kidney tissues, the peak of the Ang Ⅱ level was delayed for 6 - 8 h and the amplititude decreased in remnant kidney tissues. ②Diurnal rhythm of bmall mRNA expression in sham group was similar to that in model group. The peak of per2 mRNA was advanced by 4 h in model group. The expression of bmall mRNA was phase delayed by 4 h in BM group compared with sham group and model group. Neither per2 nor dbp mRNA showed diurnal rhythmic pattern. ③The amplitudes of BMAL1 and DBP were enhanced in model rats and the peak of PER2 and BMAL1 was advanced by 4 h in comparison with sham group. Moreover, the amplitude and peak of BMAL1 and DBP in BM group were similar to those in sham group. ④There was positive correlation in Ang Ⅱ and bmall mRNA in the kidney between sham group and model group. Conclusion Benazepril changed the diurnal rhythm of Ang Ⅱ ,clock genes and proteins in the kidney of STNx rats. Interactions of renin-angiotensin system（RAS） with clock gene

关 键 词：5 6肾切除 苯那普利 血管紧张素Ⅱ 近日节律 时钟基因 时钟蛋白 

分 类 号：R349.6[医药卫生—基础医学]