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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 the renal damage morphology and the ratio of angiotensin converting enzyme (ACE) mRNA and angiotensin converting enzyme 2 (ACE2) mRNA expression in renovascular hypertensive rats (RHR) . Methods RHR model was duplicated by two kidneys and one clip. At 6 weeks after operation, the rats were randomly divided into 3 groups: RHR group (n = 6), enalapril group (n = 6), irbesartan group The surgery group (n = 6) served as a control. Six weeks after treatment, routine HE staining was used to observe the pathological sections of kidney, radioimmunoassay was used to measure the plasma levels of angiotensin Ⅱ (Ang Ⅱ) and renin in renal tissues. Real-time quantitative reverse transcription-polymerase chain reaction And ACE2 mRNA expression. Results Compared with the sham-operation group, the blood pressure in the RHR group was significantly higher than that in the RHR group (164.4 ± 20.3 vs 115.0 ± 6.8 mmHg), renal Ang Ⅱ concentration (416.3 ± 80.7 vs 285.4 ± 58.4 ng / gpro] Activity [(0.69 ± 0.08) vs (0.43 ± 0.08) μg / (gpro · h)] (all P <0.01). Compared with RHR group, Ang Ⅱ concentration (234.5 ± 28.2) (416.3 ± 80.7) ng / gpro] and renin activity (0.35 ± 0.07) in enalapril group were significantly higher than those in RHR group (0.69 ± 0.08 μg / gpro · h) were significantly lower in irbesartan group than those in irbesartan group [(518.1 ± 87.1) vs (416.3 ± 80.7) ng / gpro] and renin activity (0.87 ± 0.17 vs 0.69 ± 0.08, μg / (gpro · h)] (all P <0.01). Compared with sham operation group, the expression of ACE2 mRNA in RHR group decreased by 47.8%, the expression of ACEm RNA increased by 140.3% and the ratio of ACE to ACE2 increased by 374.2% (all P <0.01); Compared with RHR group, ACE2 mRNA expression in irbesartan group ACE mRNA expression decreased by 56.3% and ACE-ACE2 ratio decreased by 83.7% (all P <0.01). The ACE mRNA expression decreased by 72.8% and the ACE-ACE2 ratio decreased by 79.6% in enalapril group. Compared with the sham-operation group, the RHR group showed some glomerular balloon wall fibrosis, hyalinization, wall thickening; renal artery wall thickening, hyaline degeneration, stenosis; tubular arrangement Disorders, part of the lumen visible protein tube type, interstitial inflammatory cell infiltration occasionally, enalapril, irbesartan are to improve their renal pathological damage. Conclusion The increased ratio of ACE to ACE2 in RHR kidney may be related to hypertensive renal damage. Enalapril and irbesartan may be related to the reduction of ACE2 ratio in patients with hypertension.