摘要
目的观察自发性高血压大鼠(SHR)肾脏血管紧张素转换酶2(ACE2)的表达,探讨伊贝沙坦对SHR肾脏ACE2 mRNA表达的调节作用。方法20只14周龄雄性SHR分为SHR组和伊贝沙坦组,各10只。伊贝沙坦组每只大鼠予以伊贝沙坦50 mg·kg-1·d-1灌胃,给药时间12周。同时取14周龄雄性京都种Wistar大鼠10只为对照组。SHR组和对照组给予等量蒸馏水灌胃12周。采用免疫组织化学和逆转录聚合酶链反应检测各组大鼠肾脏ACE2表达,利用放射免疫测定法检测各组大鼠血浆血管紧张素(Ang)Ⅱ浓度。结果与对照组比较,SHR组ACE2 mRNA表达显著减少(0.72±0.11对1.11±0.15);与SHR组比较,伊贝沙坦组经12周治疗后,ACE2 mRNA表达明显提高(1.03±0.13对0.72±0.11),均为P<0.05。SHR肾脏ACE2 mRNA表达与血浆AngⅡ浓度成正相关(r=0.83,P<0.05)。结论ACE2在高血压大鼠肾脏表达显著减少,可能是高血压病理生理变化之一。AngⅡ-1型受体阻滞剂伊贝沙坦上调SHR肾组织ACE2 mRNA表达,提示这可能是该药物反向调节过度激活的肾素-血管紧张素系统又一新途径。
Objective To investigate the regulation effect of irbesartan on the expression of angiotensin-converting enzyme 2 (ACE2) mRNA in the kidney of spontaneously hypertensive rats (SHR). Methods Twenty 14-week-old male SHR were randomly divided to SHR group (n= 10) and irbesartan group (n= 10) ; ten 14 week-old male WKY group were served as control. Irbesartan group was given a daily dose of 50 mg/kg irbesartan for 12 weeks by gavage and the other two groups were fed with a normal diet. ACE2 in kidney was examined by immunohistochemistry and RT-PCR. Plasma angiotensin Ⅱ in each group were estimated by radioimmunoassay (RIA). Results The ACE2 mRNA expression was significantly down-regulated in the kidney of SHR group compared with WKY group (0. 72±0. 11 vs 1.11±0. 15). After 12 weeks treatment with irbesartan, the attenuated ACE2 expression in irbesartan group was markedly enhanced compared with SHR group (1.03± 0. 13 vs 0. 72 ± 0.11) . ACE2 mRNA expression in SHR kidney was correlated significantly with plasm angiotensin Ⅱ level. (r = 0.83, P 〈 0. 05). Conclusions The remarkably reduction of ACE2 expression in the kidney of rats might be involved in the change of pathologic physiology in hypertension. Irbesartan treatment markedly increases ACE2 mRNA expression in SHR kidney and may take part in down-regulating the activated renin-angiotensin system in a new way.
出处
《中华老年医学杂志》
CAS
CSCD
北大核心
2006年第8期618-622,共5页
Chinese Journal of Geriatrics