维生素D类似物对心肌肥厚的抑制作用

Inhibited Effects of Vitamin D Analogs on Cardiac Hypertrophy

目的探讨维生素D类似物对自发性高血压大鼠(SHRs)心肌肥厚的治疗作用。方法选取20只1个月大雄性SHR,随机分成高血压对照组(C组,n=5)、洛沙坦组(L组,n=5)、帕立骨化醇组(P组,n=5)、洛沙坦与帕立骨化醇联合用药组(LP组,n=5),进行2个月不同干预。HE染色观察SHR左心室横断面变化,异硫氰酸荧光素标记的麦胚凝集素对左心室细胞膜染色观察心肌细胞变化,Image J软件测量心肌细胞直径大小。Northern blot法观察心肌细胞中心钠素(ANP)和脑钠素(BNP)mRNA的表达。Western blot法观察肾脏中肾素蛋白水平表达,实时定量PCR观察肾脏中mRNA水平表达,RT-PCR法观察心脏中肾素mRNA水平改变。结果与C组相比,P组出现左心室壁变薄,但LP组左心室壁变薄更明显,C组心肌细胞大且间质增生而LP组的细胞最小(P<0.01)、间质最少。心肌细胞中ANP和BNP的mRNA表达量在LP组最低(P均<0.05)。肾脏中肾素蛋白在L组表达水平最高、在LP组表达明显降低,肾脏中肾素mRNA在L组表达最高、在P组表达最低(P均<0.05),心脏中的肾素mRNA在L组表达水平最强、在LP组表达水平明显降低。结论维生素D类似物与洛沙坦在抑制左心室心肌肥厚中起协同作用。

Objective To study the contribution of vitamin D analogs on cardiac hypertrophy in spontaneously Hypertensive Rats. Methods Twenty male SHR rats were randomly divided into hypertension control group （ C group, n = 5） , losartan group （ L group, n = 5） , paricalcitol group （P group, n = 5） , losartan ＋ paricalcitol group （ LP group, n = 5 ） , and there rats were intervene them for 2 months. Staining cross - sections of left ventricles with HE was performeol to observe its change. Cardiomyocytes were stained with FITC labeled wheat germ agglutinin and viewed by a fluorescence microscope. Diameter of cardiomyocytes was measured by computer software Image J. The expression of ANP and BNP mRNA in cardiomyocytes were detected by Northern blot. Renin in kidney protein expression was detected by Western blot. the expression of renin mRNA in kidney was observed by real time PCR. observes the expression of renin mRNA in heart was obserred by RT - PCR. Results Compared with C group, P group＇s left ventrieular become thin and LP group＇s left ventricular become thinner, C group＇s cardiomyocytes was big and stroma hyperplasia but LP group＇s eardiomyoeytes was the smallest （ P 〈 0.01 ） and stroma was few. LP group＇s mRNA expresstion of ANP and BNP in cardiomyocytes was the lowest（ P 〈 0.05 ）. L group＇ s Renin protein in kidney expression was highest, and the expression in LP group become absolutely low. The expression of renin mRNA in kidney in L group was highest and in P group was lowest （P 〈 0.05）. The expression of renin mRNA in heart in L group is highest in LP group was lowest （P 〈 0.05）. Conclusion The combination of vitamin D analogs with losartan generates a degree of therapeutic syn- ergism in the attenuation of left ventricular hypertrophy.