脯氨酰羧基肽酶介导氯沙坦对高血压模型大鼠血管重构的抑制作用研究  

Inhibitory Effects of Prolylcarboxypeptidase-mediated Losartan on Vascular Remodeling in Hypertensive Rats

作　　者：李湘宏[1] 秦又发[2] 陈根[2] 杨晓青[2] 秦旭平[2] 

机构地区：[1]南华大学附属南华医院药剂科,湖南衡阳421001 [2]南华大学药物药理研究所,湖南衡阳421001

出　　处：《中国药房》2013年第13期1168-1171,共4页China Pharmacy

基　　金：国家自然科学基金资助项目(No.30572192;81173060);南华大学归国人员基金资助项目(No.2010XQD44)

摘　　要：目的:研究脯氨酰羧基肽酶(PRCP)介导氯沙坦对高血压模型大鼠血管重构的抑制作用。方法:取大鼠行"两肾一夹"手术建立高血压模型,分为假手术组、模型组、阳性对照组[哌唑嗪15mg(/kg·d)]和低、中、高剂量[5、15、30mg(/kg·d)]氯沙坦组,各组12只,术后第11周,后4组灌胃给药干预4周。监测术前、术后给药前和给药4周后各组大鼠的血压,检测给药4周后各组大鼠肠系膜动脉腔内径(LD)和血管中层厚度(MT)、横截面积(MCSA)、腔面积(LA)变化与PRCPmRNA及其蛋白的表达水平。结果:与术前比较,除假手术组外其余各组大鼠术后给药前血压均明显升高(P<0.01);与术后给药前比较,阳性对照组和氯沙坦组大鼠给药4周后血压均明显降低(P<0.01)。与假手术组比较,模型组大鼠LD、PRCPmRNA及其蛋白表达均明显减小,MT/LA比值和MCSA/LA比值均明显增加(P<0.01);与模型组比较,阳性对照组和氯沙坦组大鼠LD均明显增加,MT/LA比值和MCSA/LA比值均明显减小(P<0.01),氯沙坦组大鼠PRCPmRNA及其蛋白表达均明显增加(P<0.01),且与剂量呈正相关。结论:氯沙坦能有效降低大鼠血压和逆转肠系膜动脉肥厚,其作用机制可能与PRCP的表达上调有关。OBJECTIVE：To study the inhibitory effects of Prolylcarboxypeptidase（PRCP）-mediated losartan on vascular remodeling in hypertensive rats.METHODS：Rats underwent ＂two-kidney one clip＂ surgery to set up hypertensive model.Model rats were divided into sham operation group,model group,positive control group [prazosin 15 mg（/kg · d）] and losartan low-dose,medium-dose and high-dose groups [5,15,30 mg（/kg · d）] with 12 rats in each group.At 11th week after operation,the latter 4 groups were given relevant medicine intragastrically for 4 weeks.The blood pressures of rats were determined before operation,before medication postoperatively,4 weeks after medication.The changes of LD,MT,MCSA,LA,mRNA and protein expression of PRCP in rats were determined 4 weeks after medication.RESULTS：Compared with before operation,blood pressure of rats in those groups increased significantly,except for sham operation（P0.01）;compared with before medication postoperatively,the blood pressure of rats decreased significantly in positive control group and losartan groups 4 weeks after medication （P0.01）.Compared with sham operation group,LD level,mRNA and protein expression of PRCP decreased significantly in model group,and MT/LA ratio and MCSA/LA ratio increased significantly（P0.01）;compared with model group,LD levels of rats increased significantly in positive control group and losartan groups,and MT/LA ratio and MCSA/LA ratio decreased significantly （P 0.01）;mRNA and protein expression of PRCP increased significantly in losartan groups（P0.01）,relating to drug dosage positively.CONCLUSIONS：The blood pressure and mesenteric arterial hypertrophy are regressed by losartan,which may be associated with up-regulation of expression of PRCP.

关 键 词：脯氨酰羧基肽酶 氯沙坦 高血压 血管重构 大鼠 

分 类 号：TQ925.2[轻工技术与工程—发酵工程] R965[医药卫生—药理学]