血管紧张素Ⅱ调节大鼠心肌胶原的表达

Angiotensin Ⅱ Regulates the Expression of Collagens in Rat Heart

目的 观察血管紧张素(Ang)对大鼠心肌、型胶原纤维蛋白基因表达的影响,评价DMP811(新型血管紧张素1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:Ang输注;(3)组:Ang输注+DMP811管饲(3mg·kg-1·d-1)。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、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、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、型胶原蛋白沉积也较(1)组明显。Ang导致的上述改变能被DMP811完全阻断。结论 Ang通过其1型受体的介导,上调心肌、型胶原基因的表达。

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 AngⅡ. Methods Six week old male SD rats with osmotic minipump subcutaneously containing either AngⅡ or saline were used. (1) Saline infused(control) group ( n=6 ),(2) Ang Ⅱ infused group ( n=6 ). (3) AngⅡ infused and DMP811 treated (3 mg·kg -1 ·d -1 ,by gavage)group ( n=6 ).AngⅡ(200 ng·kg -1 ·min -1 ) or saline was continuously infused for 1 week.After extraction of cardiac total RNA,the levels of collagenⅠ,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 AngⅡ increased the deposits of both collagen Ⅰ and Ⅲ.The above changes caused by AngⅡ could be inhibited fully by DMP811. Conclusions AngⅡ up regulated the expressions of collagenⅠ,Ⅲ via angiotension type 1 receptor.