血管紧张素Ⅱ调节大鼠心肌胶原的表达

目的观察血管紧张素Ⅱ(AngⅡ)对大鼠心肌Ⅰ、Ⅲ型胶原纤维蛋白基因表达的影响,评价DMP811(新型血管紧张素Ⅱ1型受体拮抗剂)对其干预作用.方法6周龄雄性SD大鼠随机分为3组,每组6只.(1)组生理盐水输注;(2)组AngⅡ输注;(3)组AngⅡ输注 DMP811管饲(3mg@kg-1@d-).1周后取其心脏,采用逆转录多聚酶链反应(RT-PCR)及胶原染色的方法分别检测心肌Ⅰ、Ⅲ型胶原基因的mRNA及蛋白表达水平.结果(2)组心重(CW)、心重/体重(C/B)、胶原Ⅰ、Ⅲ基因转录水平均高于(1)组,它们分别增加(4.7±0.4)%,(4.9±0.9)%,(22.0±4.7)%和(20.6±4.9)%(P＜0.01);而且心肌Ⅰ、Ⅲ型胶原蛋白沉积也较(1)组明显.AngⅡ导致的上述改变能被DMP811完全阻断.结论AngⅡ通过其1型受体的介导,上调心肌Ⅰ、Ⅲ型胶原基因的表达.

Angiotensin II regulates the expression of collagens in rat heart

OBJECTIVE: To testify the effect of angiotensin (Agn) II on the regulation and expression of collagen I, III genes in rat heart as well as the influence of DMP811 (a novel nonpeptide selective angiotension type 1 antagonist) on the effect of Ang II. METHODS: Six-week-old male SD rats with osmotic minipump subcutaneously containing either Ang II or saline were used. (1) Saline-infused(control) group (n = 6), (2) Ang II-infused group (n = 6). (3) Ang II-infused and DMP811-treated (3 mg.kg-1.d-1, by gavage) group (n = 6). Ang II (200 ng.kg-1.min-1) or saline was continuously infused for 1 week. After extraction of cardiac total RNA, the levels of collagen I, III mRNA and proteins were measured with RT-PCR and Sirius red staining respectively. RESULTS: Cardiac weight, cardiac weight/body weight radio, the mRNA levels of collagen I, III were increased by (4.7 +/- 0.4)%, (4.9 +/- 0.9)%, (22.0 +/- 4.7)% and (20.6 +/- 4.9)% respectively, in group 2 compared with those in group 1. The analysis of collagen on Sirius red-stained sections showed that Ang II increased the deposits of both collagen I and III. The above changes caused by Ang II could be inhibited fully by DMP811. CONCLUSIONS: Ang II up-regulated the expressions of collagen I, III via angiotension type 1 receptor.