自发性高血压大鼠大、中动脉壁AT1和AT2受体表达的增龄性变化

目的以自发性高血压大鼠(SHR)为研究对象,探讨动脉血管壁胶原成分、血管紧张素Ⅱ受体(ATR)AT1和AT2亚型蛋白表达的增龄性改变。方法幼年组(7周)、成年组(26周)、老年组(51周)雄性SHR各20只,正常饮食饲养1周后,测定鼠尾动脉收缩压;胸主动脉及肠系膜上动脉(SMA)取材后,石蜡切片,Mallory染色观察壁纤维化程度,免疫组化SABC法测定ATR蛋白表达。结果 3个年龄组SHR大鼠的血压随增龄呈现明显升高(151±26)mmHg vs.(166±9.0)mmHg vs.(180±13)mmHg,P<0.05];胸主动脉和SMA壁Ⅰ型和Ⅲ型胶原纤维沉积亦随增龄增多(IA值:主动脉416±43 vs.483±74 vs.553±83,SMA 387±46 vs.425±67 vs.468±81,P均<0.05);胸主动脉和SMA壁AT1和AT2表达均随年龄增长呈增高趋势(灰度值:胸主动脉AT1 159±7.0 vs.150±8.7 vs.139±8.9,AT2 187±6.9 vs.181±9.5 vs.169±10;SMA AT1 163±11 vs.112±11 vs.128±18,AT2 188±11 vs.171±15 vs.171±13;P均<0.05),AT1/AT2比值仅在老龄组增高(幼龄及老龄组胸主动脉0.86±0.01 vs.0.78±0.08;SMA 0.85±0.07 vs.0.71±0.08,P均<0.05)。结论增龄可导致SHR成纤维细胞生长、胶原纤维沉积,血管壁局部AT1、AT2表达及二者比例改变,同时AT1由单纯的介导血管收缩作用转变为介导血管壁重塑,可能是SHR大鼠血压增龄性改变的机制之一。

Effects of aging on AT1 and AT2 expressions in the aorta and superior mesenteric artery of spontaneously hypertensive rats

Objective To investigate whether aging leads to blood vessel remodeling in the aortic artery and superior mesenteric artery(SMA) walls of spontaneously hypertensive rats(SHRs) with the changes of angiotensin Ⅱ receptor-1(AT1) and angiotensin Ⅱ receptor-2(AT2) in local artery walls.Methods A total of 60 male SHRs aged 7,26 and 51 weeks were divided into young,adult,and aged groups(20 in each group).After 1-week normal diet,the systolic blood pressure of the SHRs was measured and analyzed by a tail-cuff method.The expressions of AT1 and AT2 in arteries were detected by immunohistochemical SABC staining in paraffin sections.The degree of the sediment of collagen fibers was detected using Mallory three-color staining.Results Blood pressure of the SHRs significantly increased with aging (151±26)mmHg vs.(166±9.0)mmHg vs.(180±13)mmHg,P<0.05].Aging induced a significant increase of sediment of collagen fibers in the SHRs(IA values in aortic artery 416±43 vs.483±74 vs.553±83;in SMA 387±46 vs.425±67 vs.468±81,both P<0.05).AT1 and AT2 were expressed significantly higher with aging in the aortic artery(gray degree of AT1: 159±7.0 vs.150±8.7 vs.139±8.9; AT2: 187±6.9 vs.181±9.5 vs.169±10,both P<0.05),which was the same as in SMA(AT1: 163±11 vs.112±11 vs.128±18;AT2: 188±11 vs.171±15 vs.171±13,both P<0.05).Aging also induced the increase of AT1/AT2 ratio in aged SMAs(0.85±0.07 in young rats vs.0.71±0.08 in old ones,P<0.01),and in the aortic artery(0.86±0.01 in young rats vs.0.78±0.08 in old ones,P<0.05). Conclusion Sediment of collagen fibers induced the changes of ATR expression profiling and function in local artery walls may be one of the mechanisms of artery remodeling and increasing SBP induced by aging.