血管紧张素Ⅱ对大鼠心房纤维化及Cx40重构的影响

目的采用大鼠肾上腹主动脉部分结扎的模型,探讨血管紧张素Ⅱ(AngⅡ)对心房纤维化和缝隙连接蛋白(Connexin,Cx)40重构的影响。方法将40只雄性Wistar大鼠随机等分为对照组(C组)、腹主动脉结扎组(AB组)、结扎+贝那普利组(B组)、结扎+缬沙坦组(V组)。B组给予贝那普利20mg/kg治疗,V组给予缬沙坦40mg/kg治疗。喂养8周后处死,用放射免疫法测血浆及心肌组织AngⅡ含量,用Masson染色法和免疫组化方法检测大鼠心房纤维化程度及Cx40的分布特征,半定量分析心房纤维组织含量和Cx40的分布密度。结果与C组相比,AB组和V组血浆、心肌AngⅡ含量均明显升高(P均<0.01),而B组则无明显变化(P>0.05)。AB组心房纤维组织含量较C组明显升高(P<0.01),而Cx40分布密度减低(P<0.01),且向侧边分布增加;B组和V组纤维组织含量较AB组显著降低(P均<0.01),而两组Cx40含量较AB组增加(P均<0.01),且分布不均一程度减轻。结论AngⅡ长期升高可能是导致心房纤维化和Cx40重构的重要机制之一;贝那普利及缬沙坦可有效减轻心房纤维化和Cx40的重构。

Effects of angiotensin Ⅱ on atrial fibrosis and connexin 40 remodeling in rats

Objective To explore the effects of angiotensinⅡ(AngⅡ)on atrial fibrosis and gap junction connexin(Cx)40 remodeling in rats with their suprarenal abdominal aortae ligated partly. Methods Forty male Wistar rats were randomly and equally divided into four groups: control group(C),abdominal aorta ligated group(AB),abdominal aorta ligated rats treated with benazepril(20 mg·kg-1·d-1)group(B),abdominal aorta ligated rats treated with valsartan(40 mg·kg-1·d-1)group(V). After feed for eight weeks, AngⅡin plasma and cardiac tissue were determined by RIA. The degree of atrial fibrosis was measured with Masson staining and the distribution of Cx40 was characterized by immunohistochemistry in rats. The semi-quantitative assessment was performed to analyze the content of fibrous tissue and density of Cx40 in atrium. Results Compared with group C, the concentration of Ang Ⅱ in the plasma and myocardium in group AB and group V increased markedly(P<0.01), but those in group B had no obvious changes(P>0.05). The content of atrial fibrous tissue in group AB increased significantly compared with group C, while density of Cx40 decreased and the side to side distribution pattern increased; The content of fibrous tissue in group B and group V was diminished significantly(P<0.01)while Cx40 levels increased compared with group AB, and the degree of inhomogeneity in Cx40 distribution reduced. Conclusion It may be one of the important mechanism of atrial fibrosis and Cx40 remodeling that Ang Ⅱlevel elevated for a long time. Benazepril and valsartan can reduced the degree of atrial fibrosis and remodeling of Cx40 effectively.