摘要
目的观察依那普利、厄贝沙坦对肾性高血压大鼠(RHR)肾损害形态学和血管紧张素转换酶(ACE)mRNA与血管紧张素转换酶2(ACE2)mRNA表达比值的影响。方法采用两肾一夹复制RHR模型,术后第6周,随机分为RHR组(n=6)、依那普利组(n=6)、厄贝沙坦组(n=6),假手术组(n=6)作为对照。用药6周后,常规HE染色观察肾脏病理切片,放射免疫分析法测定血浆及肾脏组织血管紧张素Ⅱ(Ang Ⅱ)和肾素活性水平;采用实时定量逆转录聚合酶链式反应方法检测肾脏ACE和ACE2 mRNA的表达。结果与假手术组比较,RHR组血压[(164.4±20.3)比(115.0±6.8)mm Hg]、肾组织Ang Ⅱ浓度[(416.3±80.7)比(285.4±58.4)ng/gpro]和肾素活性[(0.69±0.08)比(0.43±0.08)μg/(gpro·h)]均增加(均P<0.01)。与RHR组比较,依那普利组肾组织Ang Ⅱ浓度[(234.5±28.2)比(416.3±80.7)ng/gpro]和肾素活性[(0.35±0.07)比(0.69±0.08)μg/(gpro·h)]均降低,厄贝沙坦组肾组织Ang Ⅱ浓度[(518.1±87.1)比(416.3±80.7)ng/gpro]和肾素活性[(0.87±0.17)比(0.69±0.08)μg/(gpro·h)]均增加(均P<0.01)。与假手术组比较,RHR组肾脏ACE2 mRNA表达下降47.8%、ACEm RNA的表达上升140.3%、ACE与ACE2比值上升374.2%(均P<0.01);与RHR组比较,厄贝沙坦组ACE2 mRNA的表达上升61.4%、ACE mRNA的表达下降56.3%、ACE与ACE2比值下降83.7%(均P<0.01),依那普利组ACE mRNA表达下降72.8%、ACE与ACE2比值下降79.6%。与假手术组比较,RHR组HE染色见部分肾小球球囊壁纤维组织增生、玻璃样变,囊壁增厚;肾小动脉管壁增厚、玻璃样变,管腔狭窄;肾小管排列紊乱、部分管腔内可见蛋白管型,间质内偶见炎细胞浸润,依那普利、厄贝沙坦均改善其肾脏病理损害。结论 RHR肾脏ACE与ACE2比值升高可能与高血压肾损害有关;依那普利、厄贝沙坦逆转高血压肾损害可能与降低ACE与ACE2比值有关。
Objective To observe the effects of enalapril and irbesartan on changes of renal morphology and angiotensin converting enzyme（ACEI and ACE2 ratio in renovascular hypertensive rats（RHR）. Methods RHR were induced by Two-kidney-one-clip, at six weeks after operation, rats were randomly divided into RHR group （n= 6） , enalapril group { n = 6） and irbesartan group （ n = 6 ）, sham-operation rats ） served as negative controls. After six-week treatment, the pathological sections of kidneys were observed through HE staining,the levels of angiotension Ⅱ（Ang Ⅱ ） and renin activity in kidney tissue and blood plasma were determined with radioimmunoassay; the expressions of ACE2 mRNA and ACE mRNA in kidney tissue were detected by real-time PCR. Results Compared with the sham group , blood pressure [（164.4±20.3） vs （115.0±6.8） mm Hg],Ang [Ⅱ（416.3±80.7） vs （285.4±58.4）ng/g pro] and renin activity[（0.69±0.08） vs （0.43±0.08）tg/（g pro . h）]（all P-（0.01 ） in RHR group were significantly increased. Compared with the RHR group,AngⅡ[（234.5±28.3） vs （416.3±80.7） ng/g pro] and renin activity [（0.35±0.07} vs （0.69±0.08）/lg/（g pro . h）] in enalapril group were significantly decreased {all P〈：0.01）, Ang [[ [（518. l±87.1} vs （416.3±80.7） ng/g pro] and renin activity [（0.87±0.17） vs （0.69±0.08）Mg/（g pro . h）] in irbesartan group were significantly increased （all P〈0.01）. The expression of ACE2 mRNA in RHR group kidney was decreased by 47.8% than that in the sham group, ACE mRNA expression was in- creased by 140.3M, and ACE and ACE2 ratio was increased by 3742 2%; compared with the RHR group, ACE2 mRNA expression levels in kidney were increased by 61.45%, ACE mRNA expression and ACE and ACE2 ratio were decreased by 56.3 % and 83.7 % respectively in irbesartan group （P〈0.01}, ACE mRNA expression levels in kidney and ACE and ACE2 ratio were decreased by 72.8% and 79.6% respectively in enalapril group. With HE stai-ning, the fibrosis, glassy degeneration and thickening of glomerular balloon wall, the thickening, glassy degeneration and luminal stenosis of renal arterioles, renal tubular disorder, protein casts in renal tubular lumen and interstitial infiltration of inflammatory cells were observed in RHR group, enalapril and irbesartan attenuated the above injuries. Conclusions Hypertensive renal damage may be associated with the increased of ACE and ACE2 ratio in kidney; The reversal effects of enalapril and irbesartan on hypertensive renal damage may be related to decreased ACE and ACE2 ratio.
出处
《中华高血压杂志》
CAS
CSCD
北大核心
2012年第9期872-877,共6页
Chinese Journal of Hypertension
基金
贵州省科学技术基金重点项目
贵州省优秀科技教育人才省长专项资金[(2002)3013
(2005)239]
