不同年龄自发性高血压大鼠肾脏AT_1R和AT_2R的表达

Expression of AT_1R and AT_2R in the Kidney of Spontaneously Hypertensive Rats at Different Ages

目的本研究观察不同月龄自发性高血压大鼠(SHR)肾脏AT1R和AT2R表达,初步探讨AT1R和AT2R在高血压发生、发展过程中的可能作用。方法1月龄组(S1)、2月龄组(S2)、3月龄组(S3)、6月龄组(S6)和9月龄组(S9)雄性SHR共5组,每组各6只,各组均有相应月龄匹配的Wistar-Kyoto大鼠(WKY)作对照。采用RBP-I型大鼠血压心率测定仪测量大鼠尾动脉收缩压(SBP);放免法测定血浆血管紧张素Ⅱ(AngⅡ);免疫组化染色结合计算机图像分析方法测定肾脏AT1R和AT2R表达水平。结果(1)SHR SBP随着月龄的增加而上升,S6后趋于稳定。(2)1个月后SHR血浆AngⅡ浓度均高于S1(P<0.05),而S2、S3、S6和S9之间无明显差别(P>0.05);1个月后SHR血浆AngⅡ浓度均高于相应配对的WKY组(P<0.05);而WKY各月龄组均无明显差别(P>0.05)。(3)SHR肾脏AT1R随着月份的增加而增加(P<0.05),且高于相应配对的WKY组(P<0.05)。SHR肾脏AT2R随着月份的增加而降低,S6明显降低(P<0.05),S6和S9比较无明显差别(P>0.05);且均低于相应配对的WKY组(P<0.05)。WKY各月龄组AT1R和AT2R无明显差别(P>0.05)。结论SHR肾脏AT1R表达水平比WKY高,并随着年龄的增加而递增;AT2R表达水平比WKY低,并随着年龄的增加而降低。

Objective To investigate the expression of AT1 R and AT2 R in the kidney of spontaneously hypertensive rats （SHR）at different age and to explore the role of these recepters in the development of hypertension. Methods Male SHR （n=30） were allocated to five groups by age：1） one-month-old group （S1）; 2） two-month-old group（S2）; 3） three-month-old group （S3） ;4） six-month-old group （S6） ;5） nine-month-old group （S9）. Sex- and age-matched Wistar-Kyoto normotensive rats（WKY） served as controls. The blood pressure was measured. The expression of AT1R and AT1R in the kidney was examined by immunohistochemistry and computer image analysis. Plasma concentration of angiotensin Ⅱ（Ang Ⅱ） was measured by radioimmunoassay. Results 1. An age-dependent increase of SBP was observed in SHR before six months （P〈0.05）, the SBP remained stable after the sixth month （P〉0.05）. 2. Plasma Ang Ⅱ concentration was higher in S2, S3, S6 and S9 groups than that in S1 group （P〈0.05）, and no siginificant difference was observed among S2, S3, S6 and S9 groups （P〉 0.05）. No significant difference was observed between the differently aged WKY rats （ P 〉 0.05 ）. The plasma Ang Ⅱ concentration was higher in S2,S3,S6 and S9 groups than that in the matched WKY rats （P 〈 0.05）. 3. An age-dependent increase of the AT1R was observed in the SHR kidney （ P 〈 0.05） ,The AT1R was higher in SHR than those in the matched WKY rats （ P 〈 0.05）. No significant difference was observed between differently aged WKY rats （P 〉 0.05）. An age-dependent decrease of AT2R was observed in the SHR kidneys （ P 〈 0.05 ）, which was lower in S6 rats than that in Sl rats （ P 〈 0.05 ）, and no significant difference was observed between Ss and S9 groups （ P 〉 0.05）. The AT2 R expression was lower in SHR than that in the matched WKY rats （ P 〈 0.05）. Conclusions The expression of AT1R in the kidney of SHR is increased in comparison with that of WKY rats. The expression of AT1R in the kidney of SHR is decreased compared with that in WKY rats. An age-dependent variation of AT1R and AT2R expression is observed in SHR at different ages.